Ganglion impar block is used for the treatment of chronic coccygodynia. Pulsed radiofrequency (PRF) of the ganglion impar is a promising novel technique. The aim of this study was to determine and compare the efficacy of the blockade and PRF of the ganglion impar.Thirty-nine consecutive patients diagnosed with coccygodynia and treated with a blockade or PRF of the ganglion impar were included in this retrospective study. We compared the ganglion impar block (GIB) group (n = 25) with the ganglion impar pulsed radiofrequency (GIPRF) group (n = 14) in terms of pain intensity and patient satisfaction. We applied a numeric pain rating scale (NPRS) and a Likert scale (LS).The NPRS scores in both groups had improved significantly from baseline at 3 weeks and at 3 and 6 months. However, in the sixth month, pain levels in the GIPRF group remained good, but they had returned to almost initial levels in the GIB group. Correspondingly, there were significant differences between groups in NPRS and patient satisfaction scores at 6 months (P ˂ 0.05).PRF neuromodulation provides significantly longer pain relief and reduces the risk of recurrence of pain in chronic coccygodynia as compared with blockade of the impar ganglion. Coccygodynia refers to pain and tenderness around the sacrococcygeal region. The most common etiologies are fracture, subluxation, and abnormal mobility of the coccyx. Patients usually have a previous history of trauma associated with coccygeal instability and this phenomenon triggers chronic inflammation around the sacrococcygeal joint .The ganglion impar is a solitary retroperitoneal ganglion, which is formed by the termination of paired sympathetic chains in the sacral region [3]. It provides sympathetic and visceral innervation to the lower third of the rectum, vagina, vulva, urethra, anus, perineum, and coccyx [4]. The size and location of the ganglion on the anterior surface of the sacrococcygeal joint can vary. The ventral ramus of the sacral nerve roots can also run close to the ganglion [5]. Treatment of coccygodynia is challenging because of this anatomic variability and complex somatic, visceral, autonomic, and neuropathic components [6].The most common symptom of coccygodynia is a pain in the sacrococcygeal region, which increases with sitting or standing up from a seat after a certain period. Although the presence of coccyx malposition on radiography may be useful in the diagnosis of coccygodynia, the main diagnosis is that the pain present in the coccyx region increases with palpation. The first step of treatment is conservative, which includes analgesic and antiinflammatory drugs, modifying the sitting style with the aid of ring-shaped pillows, manual manipulation of the coccyx, administration of transcutaneous electrical nerve stimulation, and physical therapy [7]. Each patient should be evaluated individually as no predictive factor has been identified for the most effective treatment modality [8]. In refractory patients, interventional treatment modalities, such as caudal epidural steroid injection, ganglion impar block (GIB), radiofrequency ablation, chemical neurolysis of the impar ganglion, and coccygectomy can be administered [9]. Blockade of the ganglion impar for the treatment of coccygodynia is an established procedure. However, the use of ganglion impar pulsed radiofrequency (GIPRF) for the treatment of coccygodynia is a relatively new approach, with limited results mostly from case reports and small series . In this study, we aimed to compare the efficacy of GIB and GIPRF in the treatment of intractable coccygodynia by analyzing the long-term outcomes in these patients.This study was performed after obtaining approval from the institutional Gülhane Training and Research Hospital ethical committee . This study was designed retrospectively. We reviewed the medical records and follow-up forms of patients who were admitted to the Department of Pain Medicine between 1 August 2016 and 1 September 2018 with a diagnosis of chronic coccygodynia. The other inclusion criteria were intractable coccygeal pain for >3 months and unresponsiveness to conservative treatments, including nonsteroidal antiinflammatory drugs, topical local anesthetics, and physical therapy. The exclusion criteria were as follows: the presence of a local or systemic infection, history of allergic reactions to drugs and contrast dye, coagulopathy, use of an anococcygeal technique, patients with missing follow-up data, and previous history of coccygectomy.A total of 39 consecutive patients treated with blockade or pulsed radiofrequency (PRF) of the ganglion impar were included in this study. All treatments were administered by the same physician who was experienced in GIB and GIPRF. All the patients provided written informed consent for the procedures. We assessed pain intensity using an 11-point numerical pain rating scale (NPRS): from 0, painless, to 10, worst imaginable pain [12]. We evaluated patient satisfaction with a Likert scale (LS), which allows the patients to define the level of agreement or disagreement  [13] at 6 months after the procedures. We assessed NPRS scores at the time of presentation and at 3 weeks, 3 months, and 6 months after the block, as well as patient satisfaction at 6 months after the block. We collected all data from the patients’ medical records and follow-up forms.The patients were placed in prone positions with a cushion beneath the abdomen to properly view the sacrococcygeal disc. We performed routine noninvasive monitoring of blood pressure, pulse oximetry, and electrocardiography, and established intravenous access. After aseptic preparation using 10% povidone-iodine, we infiltrated the skin with 2% lidocaine. In the GIB group, we introduced a 22-G spinal needle through the sacrococcygeal disc under fluoroscopic guidance along with anteroposterior and lateral imaging. We then administered radiopaque dye to confirm the accurate location of the needle tip when it reached the anterior surface of the sacrococcygeal region in the retroperitoneal space . After negative aspiration of blood and cerebrospinal fluid, we injected 2 mL of 0.25% bupivacaine with 1 mL (40 mg) of triamcinolone acetate, and then withdrew the needle slowly. In the GIPRF group, we introduced a 22-G, 10-mm active-tip radiofrequency cannula through the sacrococcygeal disc under fluoroscopic guidance. When the needle tip reached the anterior surface of the sacrococcygeal disc, we injected a radiopaque dye to confirm the needle’s position. Before performing PRF, we checked the tissue impedance, motor, and sensory responses. The expected tissue impedance was <500 ohm. The feeling of sensorial paresthesia around the sacrococcygeal region was <1 V at 50 Hz. We performed PRF at 42 °C for 120 s for 3 cycles with standard clinical PRF parameters . No medication was injected during the GIPRF procedure. All adverse events and complications were recorded on the follow-up forms.All analyses were performed with SPSS 21.0. Descriptive statistics  were used. Wilcoxon’s test was used to compare the continuous data in the dependent binary groups that were not normally distributed. The Mann–Whitney U test was used to compare the continuous data in independent binary groups, and Fischer’s final test was used to compare the discrete data. P < 0.05 indicated statistical significance.We reviewed a total of 44 files of patients who were admitted to our clinic with chronic coccygodynia. The trans-sacrococcygeal approach was undertaken for all the patients. We excluded 2 patients in whom the anococcygeal approach was undertaken, 2 patients who had a prior history of coccygectomy, and 1 patient with missing follow-up data. We administered GIB to 25 patients and GIPRF to 14 patients. The sociodemographic characteristics were similar in both the groups: 72% of the patients were female, the mean age was 44.6 years, and 77% of the patients had an antecedent trauma history (Table 1). In the GIB and GIPRF groups, the mean NPRS scores were 8.00 to 7.85 before injection, 3.36 to 3.50 in the third week, 4.04 to 3.14 in the third month, and 7.24 to 4.05 in the sixth month . There was a significant difference between groups in terms of NPRS scores at 6 months (P = 0.03). The LS scores for patient satisfaction at the sixth month in the GIB and GIPRF groups were 48% and 71.4%, respectively (P ˂ 0.001) (Table 2). We detected hypotension and bradycardia in one patient of the GIB group, which was treated with 0.5 mg of atropine intravenously in the follow-up period. No other complication or side effect was observed in either group.Blockade of the ganglion impar is an effective pain-relieving procedure used for many years for the management of coccygodynia [14]. However, PRF of the ganglion impar is a relatively novel approach for this indication [6]. In the present study, we achieved excellent pain relief in both GIB- and GIPRF-administered patients in the first three months. Nevertheless, while the pain in the GIB group started to return to baseline pain levels, the GIPRF group continued to maintain improved pain levels. PRF is a nondestructive approach that has been used for >20 years in the field of pain management, and there is increasing interest in its use recently [15–17]. Anatomically, if we begin from the head region, we can first give examples of its use in occipital neuralgia and cervicogenic headaches [18]. Subsequent treatments include suprascapular, intercostal, dorsal root ganglia, and other peripheral nerves . Apart from its use in nerves, there are also studies about the intraarticular and intralesional use of PRF . The main advantage of PRF is that it provides long-term pain control without complications [23]. Hence, in our study, we used GIPRF as an alternative to GIB to provide long-term pain relief with a low risk of complications. The underlying mechanisms of neuromodulator effects of PRF are still not fully clarified. It creates an electrical field around the active tip of the needle, which penetrates into the interior of the axons. Although the target tissue temperature is set at 42 °C, which is below the tissue destruction threshold of 45 °C to 50 °C [24], ultrastructural changes in the nociceptive axons are seen, especially in the pain-carrying A-delta and C-fibers [25]. Hagiwara et al. suggested that the analgesic effects of PRF are associated with enhancement of noradrenergic and serotonergic descending pathways [26]. Moreover, Van Zundert et al. identified an increased number of c-Fos-immunoreactive cells in the dorsal horn. Alterations of these gene products trigger long-term changes in gene expression, which is responsible for the long-term potentiation [27]. In accordance with our results, these changes might explain the long-lasting antinociception after PRF neuromodulation in the GIPRF group.For blockade and PRF of the ganglion impar, transdiscal sacrococcygeal, paramedian sacrococcygeal, and anococcygeal approaches can be attempted [28]. We used the transdiscal sacrococcygeal technique because of its low complication risk and ease of administration under fluoroscopic guidance [3]. It is almost impossible to reach the ganglion in cases where the sacrococcygeal discs are calcified and sacrococcygeal joints are fused. In the current study, we inducted a sacrococcygeal approach, and we excluded two patients in whom we could not reach the ganglion and used anococcygeal approach for them.There are variations in the anatomical locations and shapes of the ganglion impar. Furthermore, the ventral ramus of the sacral nerves can run close to the ganglion. To prevent complications such as nerve damage or neuritis, we administered GIB with local anesthesia and steroids or GIPRF instead of using radiofrequency ablation or chemical neurolytic agents [5]. According to our study, we revealed an increasing trend of improvement in long-term pain scores in the GIPRF group. Further randomized controlled studies evaluating the efficacy of GIPRF and GIB should be performed to establish an evidence-based gold-standard treatment for coccygodynia. The main limitation of this study was its retrospective design. We evaluated improvement in pain relief and patient satisfaction. Improvement in functional disabilities could be evaluated, as well. Nevertheless, our study makes a significant contribution to the literature because, to the best of our knowledge, this is the first study to compare the efficacy of block and PRF of the ganglion impar for the treatment of coccygodynia.To conclude, both the block and the PRF of the impar ganglion in coccygodynia improve pain in short-term and mid-term periods. However, in light of our preliminary study, the long-lasting effect of neuromodulation with GIPRF provides better pain relief than GIB in the long term.


Fusion prostate biopsy (FPB) has recently emerged as a popular and successful biopsy technique on diagnosis of prostate cancer. The aim of this study was to compare the pain levels in TRUS-guided standard 12-core prostate biopsy (SPB) and MpMRI-guided FPB. Patients detected with a PI-RADS (Prostate Imaging Reporting and Data System) ≥3 lesion on MpMRI underwent MpMRI-guided FPB (Group I) and the patients who had no suspected lesions or had a PI-RADS <3 lesion on MpMRI underwent TRUS-guided SPB (Group II). Pain assessment was performed using Visual Analog Scale (VAS) five minutes after the procedure. Following the procedure, the patients were asked to indicate the most painful biopsy step among the three steps. 252 patients were included in this study . The mean number of cores and the malignancy detection rate were significantly higher in Group I compared to Group II . No significant difference was found between the two groups with regard to VAS scores (p=0.070). The most painful part of the whole procedure was revealed to be the insertion of the probe into the rectum. However, no significant difference was found between the two groups with regard to the most painful biopsy step (p=0.140). FPB, with a relatively higher cancer detection rate, leads to the same pain level as SPB although it increases the number of biopsy cores and involves a more complex procedure compared to SPB. Further prospective studies with larger patient series are needed to substantiate our findings. Prostate cancer is the second most common cancer in men   . CommonPeriprostatic nerve block (PNB) is one of the most common and effective anesthetic techniques used for pain management during transrectal ultrasound (TRUS)-guided standard 12-core prostate biopsy (SPB)   , 4 . AdMultiparametric magnetic resonance imaging (MpMRI)-guided fusion prostate biopsy (FPB) has recently emerged as a popular technique with the aid of technological advancements. Despite involving a more complex procedure compared to SPB, this technique has been shown to provide successful outcomes in numerous studies   - 11 . IIn this study, we aimed to compare the pain levels in the patients that underwent TRUS-guided SPB and MpMRI-guided FPB in our clinic.This prospective study included patients that underwent prostate biopsy due to suspected prostate cancer at Department of Urology, Erciyes University, between December 2016 and January 2019. Patients detected with a PI-RADS (Prostate Imaging Reporting and Data System) ≥3 lesion on MpMRI underwent MpMRI-guided FPB (Group I) and the patients who had no suspected lesions or had a PI-RADS <3 lesion on MpMRI underwent TRUS-guided SPB (Group II). Patients with a previous negative biopsy, neurological disorders that could affect the pain level such as paraplegia or hemiplegia, and a serum total PSA level of >50ng/mL were excluded from the study. Moreover, patients that used analgesics for any reason on the day of or the day before the procedure, underwent biopsy under general anesthesia, and had such diseases as anal fissure or hemorrhoidal disease that could alter the pain threshold were also excluded from the study.Appropriate antibiotic prophylaxis was performed in each patient based on the results of rectal swabbing administered before the biopsy procedure. No bowel preparation or rectal cleansing was administered prior to the procedure. A MpMRI scan was performed without an endorectal coil in each patient .Initially, 2% lidocaine gel was applied to the anal cavity of each patient. After waiting for 10 minutes, the ultrasound probe was introduced into the rectum and PNB was performed by infiltrating 5mL 2% prilocaine  diluted 1:1 into the angle between the seminal vesicle and base of the prostate in the parasagittal plane with an 18-gauge (G) and 30-centimeter (cm) needle.TRUS-guided SPB was performed by obtaining 10-12 core samples in each patient. FPB was performed by obtaining 10-12 core samples in each patient, followed by the acquisition of 2-4 core samples for each suspected lesion detected on MpMRI (combined biopsy). All the biopsy procedures were performed using an ultrasound (US) fusion device based on rigid registration  with an endorectal single-angle probe (type: IC5-9-D).Prior to the biopsy procedure, each patient was verbally informed about the three biopsy steps  and were asked to indicate the most painful step for them after the procedure. Following the procedure, pain assessment was performed using Visual Analogue Scale (VAS)   . VAS isPatient data regarding age (years), body mass index (BMI), serum PSA levels, prostate volumes measured during the procedure, total number of cores obtained by biopsy, VAS scores, the most painful biopsy step, and histopathological examination results were recorded for each patient. Prostate volume was measured following the administration of PNB using the following formula: Height x Width x Length x 0.523.Statistical analyses were performed using IBM SPSS 22.0 . Normal distribution of data was analyzed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Descriptive data were expressed as mean±standard deviation (SD) or median (25th-75th percentile) based on the distribution pattern of the data. Variables with normal distribution were compared using Independent Samples t-test. Quantitative variables with non-normal distribution and independent groups with ordinal data were compared using Mann-Whitney U test. Categorical variables were compared using Chi-square test. A p value of <0.05 was considered significant.In this study, written and verbal consent was obtained from the patients for biopsy and study procedures. The study was approved by the Erciyes University Clinical Research Ethics Committee .2, median serum PSA level was 7.28 (5.00-9.57) ng/dL and median prostate volume was 50.00 (36.92-65.00) mm3 in 252 patients.The study included a total of 252 patients, comprising 159 (63.1%) patients that underwent FPB (Group I) and 93 (36.9%) patients that underwent SPB (Group II). Mean age was 61.99 (±6.95) years, median BMI was 26.10 (22.80-28.20) kg/mNo significant difference was found between the two groups with regard to age, BMI, serum PSA levels, and prostate volumes . However, the median number of cores and the malignancy detection rate were significantly higher in Group I compared to Group II    .No significant difference was found between the two groups with regard to VAS scores (p=0.070)   . The moOur results suggested that FPB, when administered with an effective anesthetic technique, causes no extra pain compared to the standard biopsy techniques although it increases the number of biopsy cores and involves a relatively more complex procedure.In a study conducted in 2018, Robins et al. reviewed 170 patients that underwent FPB or SPB and reported that no significant difference was found between the groups with regard to pain and discomfort   . A prevPain during transrectal prostate biopsy can be associated with the three steps of the biopsy procedure    . In ourLiterature reviews also indicate that there is a controversy in the literature as to whether the level of pain during biopsy can vary according to patient age and prostate volume   - 23 . IA recent systematic review indicated that the overall cancer detection rate was 26.3%-56.6% in SPB as opposed to 33.7%-79.5% in FPB   . SimilaOur study was limited in several ways. First, our study had a relatively small patient population. Secondly, although the duration of FPB is known to be longer than that of SPB, we did not record the durations of the procedures and thus could not evaluate the association between the duration of the procedure and pain. Thirdly, we did not assess the VAS scores separately for each of the three steps of the procedure  and only asked the patients to indicate the most painful step after the procedure. As a result, we could not perform an objective evaluation on the biopsy steps. Finally, the location of the suspected lesion may be important for pain felt during the biopsy. In particular, sampling from the anterior region or central zone may cause more pain as it is more difficult to reach. Another limitation of this study was the lack of statistical comparison on subject of lesion localization/pain levels due to insufficient number of patients.Despite that MRI-US fusion and taking additional cores prolonged the predicted duration of FPB which has higher cancer detection rate comparing with SPB, pain level during FPB was similar to SPB. We consider that these drawbacks of FPB do not have any adverse effects on pain. Further prospective studies with larger patient series are needed to substantiate our findings.


Introduction: Muscle pain, fatigue, and concentration problems are common among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These symptoms are commonly increased as part of the phenomenon of postexertional malaise (PEM). An increase in the severity of these symptoms is described following physical or mental exercise in ME/CFS patients. Another important symptom of ME/CFS is orthostatic intolerance, which can be detected by head-up tilt testing (HUT). The effect of HUT on PEM has not been studied extensively. For this purpose, we assessed numeric rating scales (NRS) for pain, fatigue, and concentration pre- and post-HUT. As pain is a core symptom in fibromyalgia (FM), we subgrouped ME/CFS patients by the presence or absence of FM.Methods and Results: In eligible ME/CFS patients who underwent HUT, NRS of pain, fatigue, and concentration were obtained pre-HUT, immediately after HUT, at 24 and 48 h, and at 7 days posttest. We studied 174 ME/CFS patients with FM, 104 without FM, and 30 healthy controls (HC). Values for all symptoms were unchanged for HC pre- and post-HUT. Compared with pre-HUT, the three NRS post-HUT were significantly elevated in both ME/CFS patient groups even after 7 days. NRS pain was significantly higher at all time points measured in the ME/CFS patients with FM compared with those without FM. In ME/CFS patients, the maximum fatigue and concentration scores occurred directly post-HUT, whereas pain perception reached the maximum 24 h post-HUT.Conclusion: NRS scores of pain, fatigue, and concentration were significantly increased even at 7 days post-HUT compared with pre-HUT in ME/CFS patients with and without FM, suggesting that orthostatic stress is an important determinant of PEM. Postexertional malaise (PEM) is one of the criteria of chronic fatigue syndrome (CFS)  and the Fibromyalgia (FM), a disease characterized by fatigue and prominent widespread musculoskeletal pain , 13, is Impairments in cognitive functioning, such as memory problems or concentration issues, are among the most frequently reported symptoms of ME/CFS. Patients classify the cognitive problems as equally debilitating compared with the physical symptoms that accompany this disease. One of the best-studied aspects of ME/CFS is cognition. In a meta-analysis of 50 studies using a total of 80 cognitive tests with 79 different scores, of 8 cognitive domains described, reaction time and attention were the only two domains with a moderate-to-large significant difference between ME/CFS patients and healthy controls (HC) . Thus, cIn a previous study in ME/CFS patients, we demonstrated that the orthostatic stress of a head-up tilt test (HUT) resulted in a significant reduction in cerebral blood flow (CBF) and that the blood-flow reduction was associated with the onset of worsening of pain, fatigue, and concentration problems —all charIndividuals diagnosed with ME/CFS, who underwent HUT at the Stichting CardioZorg between November 2014 and April 2018 because of a clinical suspicion of OI and in whom a complete set of the NRS was available, were included in this study. This cardiology clinic specializes in diagnosing and treating adults with ME/CFS. ME/CFS was considered present if participants met both the criteria for CFS , taking The study was carried out in accordance with the Declaration of Helsinki. The use of clinical data for descriptive studies (PT1450) and the use of HC (P1411) were approved by the ethics committee of the Slotervaart Hospital, the Netherlands. All patients and HC gave written informed consent.The study and measurements were performed as described previously , 18, 19.Patients and HC were presented with a paper with an NRS for pain with the numbers placed vertically. Participants were instructed to rate their pain level ranging from 0 to 10 –22. On tpost hoc Tukey correction where appropriate. Nominal data were compared using the chi-squared test with a 3 × 2 table. Paired data were analyzed using the paired t-test or Wilcoxon signed ranks test where appropriate. Groups were compared using the Kruskall Wallis test for unpaired data. A post hoc analysis with Dunn's test for multiple comparisons was done where significant differences were present. For non-parametric data within group comparisons, we used the Friedman test. Linear regression was performed to assess the relation between measurements . A p-value of < 0.01 was considered significant.Data were analyzed using the statistical package of Graphpad Prism version 8.2.4 . All continuous data were tested for normal distribution using the Kolmogorov–Smirnov normality test and presented as mean  or as median  where appropriate. Variables that were not normally distributed were tested for skews with histograms. For variables with evenly distributed skews, we compared groups using an ordinary or mixed two-way ANOVA with n = 8) or did not undergo a tilt test (n = 24). None of the patients had a psychiatric history with the exception of the psychiatric diagnosis of undifferentiated somatoform disorder. This diagnosis is often used by psychiatrists to characterize ME/CFS. A total of 336 individuals with diagnosed ME/CFS and OI underwent HUT and NRS assessments during the study period. Included patients did not participate in a study on working memory. Included patients were part of a previously reported study on pain pressure thresholds . We excluded patients who did not complete the 24-h, 48-h, and 7-day NRS scores . No patients used heart rate and/or blood pressure targeting drugs, and no patient had a body mass index (BMI) >37 kg/m2 and needed to be excluded for that reason. This left 278 ME/CFS patients to be analyzed. FM was present in 174 (63%) patients; 104 (37%) did not meet the criteria for FM. As part of the ME/CFS criteria, patients were asked about the presence of muscle pain complaints. In the FM- group of ME/CFS patients, 75/104 (72%) complained of muscle pains; in the FM+ group of ME/CFS patients, all patients 174/174 (100%) reported muscle pains. One hundred six (38%) ME/CFS patients used neuropathic pain medication with 20 (19%) in FM- patients and 86 (49%) in FM+ patients. No differences in scales were found in both groups with and without FM for patients using neuropathic pain medication and those who did not (data not shown). As expected, the WPI was significantly higher in FM+ ME/CFS patients compared with ME/CFS FM- patients . The SS scale score was not significantly different between FM+ and FM- groups . In the FM- group (n = 104), 49 patients had a normal heart rate and blood pressure response to HUT, 24 had delayed orthostatic hypotension, and 31 had postural orthostatic tachycardia syndrome (POTS). No patients developed presyncope or syncope during HUT. In the FM+ group (n=174), 77 had a normal heart rate and blood pressure response to HUT, 24 had delayed orthostatic hypotension, and 73 had POTS. No patients developed presyncope or syncope during HUT. A chi-squared test on the division of hemodynamic HUT results vs. the absence or presence of FM (in a 3 × 2 table) was not statistically significant. No significant relations were found between the reduction in percentage of CBF and NRS for pain, fatigue, or concentration at all time points assessed (data not shown).A total of 400 patients visited the clinic during the study period. We excluded 32 individuals who did not meet criteria for the diagnosis of ME/CFS. Another 24 ME/CFS patients were excluded because they had no orthostatic intolerance in daily life  and higher end of HUT heart rates compared to HC (both p < 0.0001). ME/CFS patients without FM were significantly taller compared to ME/CFS patients with FM (p < 0.001), but weight and BMI did not differ. The male/female ratio was lower in the patient group with FM compared to without FM (p < 0.005). Disease duration did not differ between the ME/CFS patients without FM and with FM (p = 0.52). The ME/CFS subgroups were similar on all other variables.p < 0.0001). At all measured time points , the NRS for pain differed significantly between the ME/CFS patients without FM and with FM . (A), for fatigue (B), and for concentration (C) over time.p < 0.0001]. In the ME/CFS FM- group, there was no significant difference in the NRS for pain between the patients using neuropathic analgesics or not (p = 0.07). The NRS for fatigue did not differ significantly between the two ME/CFS groups at any time point (p ranging from 0.08 to 0.02), nor did the NRS for concentration differ at any time point (p ranging between 0.33 and 0.01). There was no difference in the NRS for fatigue or concentration in the ME/CFS patients using neuropathic analgesic medication or not (data not shown). There were no significant differences between males and females in the groups with and without FM for the NRS data on pain, fatigue, or concentration (data not shown).A subgroup analysis shows a difference in pre-HUT NRS for pain between ME/CFS patients with FM using neuropathic pain medication compared to those without. Despite the use of neuropathic analgesics, in the ME/CFS patient group with FM, the median NRS for pain was significantly higher in the patients using neuropathic analgesics than without neuropathic analgesics [median 6 (4–7) vs. 4 (2–6), p < 0.0001). Tilt testing was associated with a significant increase in fatigue and concentration problems in both ME/CFS patient groups, but we did not identify a progressive increase over the following 24 h.p = 0.004). In ME/CFS patients with and without FM, all three NRS scores were significantly higher 7 days post-HUT compared with pre-HUT (p ranging from 0.004 to < 0.0001).CBF decline was 27 (8%) in the complete group. No significant relation was found between CBF reduction and differences in NRS for pain, fatigue, or concentration (data not shown).To the best of our knowledge, this is the first study in ME/CFS patients to examine the influence of HUT on self-reported symptoms of PEM. We used NRS to assess changes in the severity of characteristic PEM symptoms of pain, fatigue, and concentration and to track the duration of these symptoms after the orthostatic stress imposed by a HUT. The study had several novel findings. First, scores for pain, fatigue, and concentration were significantly higher at baseline (pre-HUT) in all ME/CFS patients compared with HC. Second, all three NRS scores were significantly higher at all time points after HUT compared with pre-HUT in both ME/CFS patients groups. Third, ME/CFS patients with FM had significantly higher NRS pain scores than ME/CFS patients without FM at all time points. Fourth, maximum fatigue and concentration abnormalities occurred directly post-HUT, whereas pain perception reached a maximum 24 h posttest with an additional increase in pain scores from directly post-HUT to 24 h after testing. Fifth, PEM as defined by higher NRS scores of pain, fatigue, and concentration still persisted 7 days after HUT. Finally, no relation was found with the reduction in CBF during HUT and a difference in either of the NRS scales at all time points, and also, no relation was found with the maximal observed difference in NRS.PEM has been described to occur after physical exercise , 23, 24,Blackwood et al. describe the onset of PEM occurring shortly after the trigger , and sevHC report recovery within 1 or 2 days following physical or cognitive exertion. In contrast, < 31% of ME/CFS patients reported having returned to their prestressor baseline state after 1 to 2 days, and 60% of ME/CFS patients still experienced PEM symptoms after 1 week , 26. Ourn-back test, decreased immediately after HUT (In a recent study, we show that worsening of pain, increased fatigue, decreased concentration, and increased dizziness or light-headedness were all experienced significantly more frequently during HUT by those with ME/CFS compared to HC . The incfter HUT . Furtherfter HUT . We, thefter HUT . It is pIn the present study, FM was considered part of the symptomatology of ME/CFS with more extensive and severe muscle pains as in FM negative ME/CFS individuals. Whether FM has the same underlying pathophysiology as ME/CFS has been discussed over many decades. Some authors have opinioned that FM and ME/CFS cannot be differentiated , 38. Wesn-back testing, is diminished post-HUT compared with pre-HUT. This may reduce carryover effects of NRS ratings. In this study, a numeric rating scale ranging from 0 to 10 was used. A large variety of rating scales and anchors are used in previous studies: For an overview the systematic literature, see the review of Hjermstad et al. (Follow-up NRS ratings may have been influenced by ME/CFS patients remembering previous ratings. On the other hand, we have previously shown in ME/CFS patients that memory, as assessed by d et al. . The conNRS for pain, fatigue, and concentration were significantly increased up to 7 days after orthostatic stress testing in ME/CFS patients. NRS for pain in patients with FM were all significantly higher than in patients without FM. Our data show that an orthostatic stressor is an important determinant of PEM.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics committee of the Slotervaart Hospital, the Netherlands. The patients/participants provided their written informed consent to participate in this study.CC and FCV conceived the study and collected the data. CC performed the primary data analysis. PR, FWAV, and FCV performed secondary data analyses. All authors were involved in the drafting and review of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Hence, the TPE program presented was effective in reducing pain and disability in patients with PFPS.The health crisis caused by COVID-19 has had a huge impact on the provision of physiotherapists’ services during the pandemic. Patellofemoral pain syndrome (PFPS) is a major health problem and one of the most common causes of pain in the front of the knee in outpatients. The objective was to evaluate the effectiveness of a therapeutic physical exercise (TPE) program supervised by a physiotherapist using telematic channels in reducing pain and disability in a sample of 54 patients with PFPS in the Physiotherapy Service of the San José de la Rinconada Health Center (Seville). Subjects were evaluated pre- and post-intervention (4 weeks—12 treatment sessions). An analysis was made of perceived pain—using the visual analog scale (VAS) and the DN4 neuropathic pain questionnaire—and functional balance—through the Kujala Score test and the Lower Extremity Functional Scale. The supervised TPE program in patients with PFPS produced a reduction in pain: VAS F The period of time covering the present study is unprecedented. On 14 March 2020, the Government of Spain decreed a state of emergency, thereby beginning a period of confinement in order to stop the spread of the SARS-CoV-2 virus. This situation forced face-to-face care of patients attending the Physiotherapy Rooms in Primary Care Centers on an outpatient basis to be cancelled [It was a question of developing a labor of health education in the population being cared for by said physiotherapy rooms. Explaining the basic measures of prevention of the spread of the virus  was necessary, as well as eliminating the techniques that would require contact, whilst at the same time providing self-management and self-care tools that matched the pathology of each patient, all of this while prioritizing telecare, recurring to telematic resources  . Some stPatellofemoral pain syndrome (PFPS) is a common musculoskeletal problem, characterized by pain in the front of the knee and tending to become chronic . AlthougPFPS has been associated with osteoarthritis of the knee and a high body mass index, but in a recent study, it was observed that this is not true in adolescents . PatientPFPS continues to be one of the most common and challenging musculoskeletal issues facing physiotherapists and sports medicine professionals .Even though the pain associated with PFPS is characteristic, the cause of this pain remains unknown. Traditionally, PFPS has been related to damage of the articular cartilage; however, we know that articular cartilage is aneural . There eThe lack of understanding of the etiology and pathology associated with patellofemoral pain and dysfunction is reflected in the great number of therapeutic options to deal with PFPS. Conservative treatments are common, above all initially, and physiotherapy is one of the commonest interventions used .Physiotherapeutic treatments often include the strengthening of the vastus medialis muscle of the quadriceps to promote active stabilization of the patella inside the trochlea of the femur, as well as manual therapy procedures, patellar realignment through taping, stretching, and therapeutic exercise ,13,14. ATherapeutic physical exercise (TPE) constitutes one of the most valuable tools in our therapeutic arsenal. Adequate prescription tailored to each patient depending on their pathology, prior state of health, and prior levels of physical activity is a demand that the health system and society places on our backs. This entails the configuration of the physiotherapist as an expert in TPE. They must supervise and optimize the TPE program, adapting it to each patient, monitoring the prior and aspirational levels of physical activity in terms of both quantity and quality. In addition, the physiotherapist must identify any psychosocial barriers that might hinder the adherence of patients to the prescribed TPE programs. In short, the physiotherapist becomes the guide of the patient who must take the reins of their health and take on a proactive role in the face of their pathology ,15.TPE and the integration of individual and group health education, in the activity of the primary care physiotherapist, afford greater control of repetitive demands on physiotherapy in the medium-term. Hence, supervised TPE has been hailed as one of the most effective tools in resolving problems deriving from chronic conditions where the reduction of pain and disability are the main objectives to be achieved . The purhttp://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377666&isReview=true and found to be in agreement with the Declaration of Helsinki.The present study is a longitudinal and prospective clinical trial conducted in the Physiotherapy Service of the San José de la Rinconada Health Center , dependent on the Andalusian Health Service. This study was supervised by the institutional ethics committee CEI University Hospital Virgen Macarena and Virgen del Rocio, with ethics approval number 41255cfcgab78019fga8501bb354b0ba4b15a804, registered in the Australian New Zealand Clinical Trials Registry: ACTRN 12619001457134, available at The target population that this protocol was aimed at was made up of all patients diagnosed with unilateral or bilateral PFPS belonging to the health area of the Basic Health Area of la Rinconada (Seville), with over 36,000 potential users. Inclusion criteria were patients diagnosed with PFPS of over a 6 month evolution, aged between 18 and 70 years. The exclusion criteria were presenting cognitive alterations and having undergone conservative or surgical treatment of the affected knee less than 6 months previously.The convenience sampling method was used based on previous studies , an apprMeasurements of the different variables of the study were made at two times, at the beginning thereof and after a four-week period, which coincided with the end of the intervention or treatment plan (12 home-based TPE sessions supervised by the physiotherapist via telematic channels).perception of pain by the visual analog scale (VAS) which consists of using a validated scale, 10 cm long (0–10), where subjects place themselves from (0) lack of pain to (10) the worst pain bearable; (ii) perception of neuropathic pain, established through the DN4 questionnaire [functional disability, quantified using the Kujala Score [The dependent variables considered in the heart of our research were (i) the ionnaire ; (iii) fla Score  and the la Score ; and  ×100). In accordance with previous studies [ studies , particiThe sample size calculation was based on the detection of (1) an improvement of 15% in self-perceived pain intensity  and (2) The statistical analysis of the data was carried out using PSW Advanced Statistics  version 24.0. Data were reported as mean (standard deviation) and confidence intervals (IC 95%). Firstly, the normal distribution of variables was verified by the Shapiro–Wilk test after descriptive analysis. The Levene test was used to assess the homogeneity of variances. Linearity was assessed by bivariate dispersion graphics of residual values observed from the expected values. Comparisons between groups were made for demographic and clinical data of reference using Student’s t-test for continuous variables and Pearson’s chi-square test for categorical variables. All analyses followed the intention-to-treat principle, and the groups were analyzed as randomized.2) was used to calculate the effect size . Statistical significance was determined at p < 0.05.Differences in the measurements were detected by analysis of covariance (ANCOVA) to evaluate each dependent variable by age, height, weight, and body mass index, and as a variable factor the group (group TPE versus C). Eta square (ηn = 54), 26 men and 28 women; mean age (SD) was 51 years (10.1). Of the affected knees, 29 were right (54%) and 25 left (46%). Of the subjects, 24 had an educational level of primary studies (44%); 18, secondary (34%); and 12, university (22%). Of the sample subjects, 38 were employed in the service sector (82%) and 10 in construction (18%).A total of 60 subjects, aged between 25 and 67 years, were selected for the trial. After the inscription phase, the final sample included 54 individuals (In relation to the patient diagnoses: 23 with patellar tendinitis (44%), 21 with gonarthrosis (40%), 7 with chondromalacia patella (12%), and 3 with bursitis (4%) took NSAIDS and analgesics, while 28 subjects (52%) took nothing.p > 0.05), confirming that the groups had equivalent values at the beginning of the study.Although the knee extension variable was measured by goniometric measurement, as all the knees in the study presented a value = 0°, or full extension, it is neither presented nor analyzed in the present study.1, 53 = 4.77 (p = 0.001) η2 = 0.33 and DN4 F1, 53 = 6.99 (p < 0.001) η2 = 0.42; and in the knee disability index: LEFS: F1, 53 = 4.38 (p = 0.002) η2 = 0.31 and KUJALA: F1, 53 = 10.58 (p < 0.001) η2 = 0.52; as well as, finally, in range of movement: Flexion: F1, 53 = 6.35 (p < 0.001) η2 = 0.50. No statistically differences were found between before- and after-treatment measurements regarding the use of basic analgesic drugs. Finally, it must be considered that no side effects were observed.Statistical significance was found in favor of the experimental group in the between-groups comparison and in the interaction in the covariables age, height, weight and body mass index, in both the perception of pain: VAS FIn this study, we evaluated the effectiveness of a telematic TPE program, supervised by a physiotherapist, in reducing pain and disability in patients with PFPS. In all participants, a significant improvement was observed in pain intensity, range of movement, and disability from baseline to four weeks of treatment, according to VAS, LEFS, DN4, and KUJALA indices.According to the most recent systematic reviews on the approach to PFPS, TPE is by far the most used therapeutic alternative . Both duIn the abovementioned reviews, the primary option is pointed out as eccentric muscle work, demonstrating a more important improvement in functional balance, as well as patient satisfaction, than other alternatives . This efThis makes it absolutely essential to carry out more comprehensive studies in the future ,27. MeanOne of the limitations of our study was the relatively short-term follow-up of four weeks due to the lack of adherence to the treatment of our subjects, which in our case was limited to three subjects (who did not finish the study) per group.Another limitation was the methods used for telecommunications, i.e., phone and email  but not videoconference. It is obvious that by increasing the attractiveness of home-based programs, we can facilitate patient adherence to tele-rehabilitation .One of the strengths of our study was the fast adaptation of the physiotherapy service to the pandemic, with low resources available, so as not to interrupt the treatment of patients. Another of the strengths is the similarity between our participants’ characteristics and those of participants in other studies. This may help other researchers to achieve a common conclusion by reviewing these study results.The perceived pain in patients with PFPS after the application of a TPE protocol supervised by a physiotherapist via telematic channels was reduced on average by 1/10, measured using the VAS and DN4 scales.Application of TPE supervised by a physiotherapist via telematic channels was effective and produced changes in the degree of disability of patients afflicted with PFPS measured through the LEFS with an increase of 15 points, rising from 45 to 60.Measurement of this disability using the KUJALA questionnaire presented a mean reduction of 20 points, going from 49 to 69.Finally, it was determined that range of movement was increased by an average of 9°.It can be concluded, therefore, that therapeutic exercise supervised by a physiotherapist via telematic channels demonstrates greater effectiveness in pain reduction and disability in patients afflicted with PFPS than merely providing information sheets to the patient.


Surface electrical stimuli were delivered to the foot in a stepwise incremental and decremental manner. The surface electromyographic activity was recorded from the ipsilateral tibialis anterior muscle. Fibromyalgia patients reported significantly higher scores for psychological distress and pain-related disability and a significantly lower score for perceived state of health compared to the matched controls. The subjective pain ratings were significantly higher in patients. The NWR thresholds were similar to the controls. In the patients, but not in controls, the NWR thresholds and subjective pain ratings were significantly correlated. Our results showed an increased subjective pain sensitivity in fibromyalgia, but we found no evidence for spinal sensitization based on the reflex measures.The nociceptive withdrawal reflex (NWR) is used to probe spinal cord excitability in chronic pain states. Here, we used an automated and unbiased procedure for determining the NWR threshold and compared the reflex thresholds and corresponding pain ratings in a well-characterized cohort of fibromyalgia ( The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex evoked by painful cutaneous stimuli. Early studies show that the cutaneous noxious electrical stimulation of the distal lower leg elicits a reflex of muscle contraction and inhibition, resulting in the withdrawal of the limb from the stimulus ,2,3. TheTo elicit the reflex, most studies use the electrical stimulation of the sural nerve distally at the ankle and record the muscle activity of the short head of the ipsilateral biceps femoris muscle ,7,8,12. The reflex afferent is generally presumed to be of the thinly myelinated Aδ type  ,18. SeveFibromyalgia is characterized by chronic and generalized hyperalgesia according to the American College of Rheumatology (ACR) criteria of 1990 , which iThe study was part of a larger effort to characterize patients with fibromyalgia. The study was granted ethical approval by the Linköping University Ethics Committee . All the participants gave their written informed consent, and the study was performed in accordance with the Helsinki Declaration.Thirty-three female fibromyalgia patients and 31 age-matched female controls between 22 and 56 years of age were eligible to participate. The age-matched female controls were recruited through advertisements in newspapers, and the fibromyalgia group consisted of patients from the Pain and Rehabilitation Centre at the University Hospital in Linköping, Sweden. One patient and two controls did not show up for the experiment. In summary, 32 patients and 29 controls were studied.During the study, five patients and one control discontinued after testing the first limb. One patient did not complete the tests on the first limb but finished the second one. In all these cases, a high level of discomfort was reported during the experiment. In one control, the result of the second limb had to be discarded due to technical issues. Accordingly, a bilateral study was conducted in 26 patients and 27 controls, and in the remaining participants only one limb was studied. Testing was performed bilaterally to examine intra-individual differences in NWR thresholds. The NWR thresholds were successfully measured in 29 patients and 21 controls.The inclusion criteria of the patients were female gender, age 20 to 65 years, and fibromyalgia according to the 1990 ACR criteria . Revised2; kg/m2). Blood pressure (mm Hg) was also measured.All the subjects were asked to refrain from caffeine and nicotine consumption for 12 h and heavy exercise for 48 h before the experiment. All the subjects went through a physical examination and their medical history was taken by a physician at the Pain and Rehabilitation Centre. The clinical examination ensured that the patients fulfilled the criteria for fibromyalgia according to the 1990 ACR criteria . For allAll the recordings were done during the daytime, either in the morning or afternoon. Both lower limbs were studied consecutively in the same experimental sitting.All the subjects answered a health questionnaire, including age (years), current pain intensity, psychological distress, disability aspects, and quality of life aspects. In the fibromyalgia group, the duration of the disease (time since diagnosis) was also noted.The current pain intensity was registered using a numeric rating scale with anchor points 0 (denoting no pain) and 10 (denoting the worst possible pain).The Hospital Anxiety and Depression Scale (HADS) comprises seven items in each of the two subscales: depression (HADS-D) and anxiety (HADS-A) symptoms ,41. BothThe Pain Disability Index (PDI) consists of seven items, and the subjects rate how much pain interferes in these seven areas of life activity: family/home responsibilities, recreation, social activity, occupation, sexual behavior, self-care, and life-support activity ,44. EachThe European Quality of Life instrument (EQ-5D) captures a patient’s perceived state of health ,46,47. I2. The cathode was an Axelgaard PALS 895,240 hydrogel self-adhesive electrode containing a stainless-steel conductive fabric with a sensor area of 4500 mm2. A constant current stimulator was used with a maximum output current of 16 mA at a maximum compliance voltage of 120 V . The two channels were connected in parallel, thus providing a maximum current of 32 mA at 120 V. The electrical stimulus composed of a train of five square wave pulses with a pulse width of 1 ms and a pulse frequency of 200 Hz—a stimulus train that is shown to effectively elicit the NWR [Electrical stimuli were delivered to the foot with the anode attached to the mid-foot arch and the cathode attached to the dorsum of the foot. The anode was an Ambu Neuroline 700 10-J/12 silver/silver chloride self-adhesive gel electrode with a sensor area of 263 mm the NWR ,49. The  the NWR . All the2; 3M, St. Paul, MN, USA). The active electrode was attached to the skin of the lower leg at a point one-third of the length of the tibialis anterior muscle from the proximal demarcation of the muscle belly palpated at isometric contraction. The reference electrode was attached to the muscle 6 cm distal to the active electrode. The ground electrode was attached to the distal lower leg between the reference electrode and the ankle. Before each test, the impedance on all the electrodes (both stimulating and recording) was noted. To reduce the electrode resistance, the skin was treated with sandpaper and washed with lukewarm water. The electrodes were connected with shielded lead wires (MLA2503 and MLA 2340) to an FE 232 amplifier and a PowerLab 4/26 data acquisition system .The NWR response was recorded on the ipsilateral tibialis anterior muscle. Three self-adhesive gel electrodes were used for active, reference, and ground recordings  to enable automatic NWR threshold determination based on the method suggested by Rhudy et al. . The maxThe stimulus intensity was increased in 2 mA steps starting at 1 mA. When a successful muscle response was recorded , the intensity was decreased with steps of 1 mA until the muscle response disappeared. The stimulus intensity was then increased with increments of 0.5 mA until a second successful muscle response was recorded. Then, the intensity was decreased with steps of 0.5 mA until the response disappeared. The intensity was again increased with steps of 0.5 mA until a third muscle response appeared. The mean value of the stimulus intensities eliciting the three successful muscle reflex responses was calculated and used as the NWR threshold. The stimulation procedure continued either until three successful muscle reflex responses were detected, until the stimulus intensity reached 30 mA, or until the subject asked us to stop.Immediately after receiving each stimulus , the subjects were asked to rate how it felt on a graded scale ranging from 0 (no feeling) to 10 (worst imaginable pain), with four taken as the liminal value for pain and thus considered as the pain threshold . The scat-test was used to assess the between-group differences of independent variables. A paired t-test and Wilcoxon signed-rank test were used for parametric and non-parametric paired analyses, respectively, for in-group comparisons of the 1st and 2nd limbs (NWR thresholds and pain ratings). A p-value <0.05 was considered significant in all the statistical analyses.IBM SPSS Statistics 24  was used for a statistical analysis. Parametric descriptive statistics were used for the continuous normally distributed variables. For the non-normally distributed continuous data, ordinal and categorical variables, non-parametric descriptive statistics and procedures were used. The Shapiro-Wilk test was used to check for normality and skewness and kurtosis values >+3 or <−3 indicated a non-normal distribution. Levene’s test was used to check for the homogeneity of variance when comparing the two study groups. A Student’s n = 25) used at least one pain-relieving medication , most commonly paracetamol (n = 17), but also NSAIDs (n = 8) and opioids (n = 7). Selective serotonin reuptake inhibitors , and serotonin–norepinephrine reuptake inhibitors  were also used as well as Amitriptyline (n = 9) and Gabapentin (n = 2). In the control group, one subject used Amitriptyline, and another used Sumatriptan. All the subjects were asked to refrain from pain-relieving medication for 48 h before the visit.The patients had on average 16 (SD 3) tender points and a mean disease duration (time from diagnosis) of 5.8 (SD 5.6) years. The BMI was significantly higher in the patient group compared to the controls . While tThe NWR thresholds were successfully measured in 29 patients and 21 controls. In 17 patients and 12 controls, two values were obtained (one from each limb), and in these cases the mean of the two values was considered as the subject’s reflex threshold. The threshold values were normally distributed in both the groups and showed a similar variance.The mean NWR threshold did not differ between the study groups, and a large spread of the individual values was seen in both the patients and the controls . There wNo significant correlations existed between the NWR thresholds and the psychometric scales  or the number of pain-relieving medications, either in all the subjects taken together or in the two study groups.The impedance of the stimulating electrodes remained high during the study, in particular on the electrode attached to the sole of the foot. However, no significant difference in impedance values was seen between the groups .The subjective pain ratings were significantly higher in the patient group compared to the healthy controls . There wIn the current study, we compared the thresholds for eliciting the NWR in fibromyalgia patients and matched healthy controls. The strength of the current study was the use of an automated and unbiased procedure for determining the NWR thresholds in a well-characterized cohort of fibromyalgia. We found no statistical difference in the NWR thresholds between the two groups. Large inter-individual variability in the NWR thresholds was seen among both patients and healthy controls. The patient group included the lowest threshold values as expected, but also somewhat surprisingly, the highest ones . This isAccording to the ACR criteria of 1990 , the diaIn fibromyalgia, conditioned pain modulation is dysfunctional , and temDuring the NWR determination procedure, all the subjects were asked to rate how they perceived the stimuli. The patient group rated higher pain compared to the healthy controls, indicating a higher subjective pain sensitivity in fibromyalgia. Both groups received a similar level of electrical stimulus intensity, therefore this cannot explain the different degrees of pain. Increased pain sensitivity is a characteristic feature of fibromyalgia ,31, and Several previous studies report a close correlation between the NWR threshold and the subjective pain threshold; some of them even show a linear correlation ,5. In thA limitation of the custom-designed software for automatic NWR threshold determination was that it did not measure the current actually delivered but rather calculated the value based on the assumption that the impedances were sufficiently low. Despite this, the NWR thresholds reported here are similar to other studies ,14,15. TIn conclusion, automated NWR threshold measurements in fibromyalgia patients and healthy controls revealed no significant differences between the groups, suggesting that spinal sensitization is not a prominent feature of fibromyalgia. However, fibromyalgia patients perceived the stimuli as more painful compared to the healthy controls, suggesting abnormalities at the perceptual level.


Spine metastasis is a common occurrence in cancer patients and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life.This is a single-center, prospective, randomized, controlled trial in patients with spine metastasis from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum will be randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients will be treated with EBRT to a dose of 20–30 Gy in 5–10 fractions. The target parameters will be measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments.The primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastasis, defined as complete or partial pain relief  at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL.NCT04375891. Registered on 5 May 2020.ClinicalTrials.gov  Metastasis to the spine is a common complication of cancer, with approximately 40% of patients developing clinically significant disease. In autopsy series, up to 90% of patients with metastatic cancer have been identified as having micrometastatic spine disease . Bone pap = 0.027) and overall pain response  were observed [Radiofrequency ablation, with or without percutaneous vertebral augmentation (RFA/PVA), has been used to treat pathologic fractures associated with spine metastasis with high rates of initial pain response . Using tThe primary objective of this randomized, controlled trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to EBRT alone for patients with spine metastasis. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall quality of life (QOL).This study is a single-center, prospective, randomized, controlled trial of patients with spine metastasis with two arms. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines  and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments . The treatment allocation scheme will be used for randomization to balances these patient factors . Within The target population for this trial includes patients with metastatic disease to the spine, between T5 and L5, as detected by any imaging study. There is no limit on the maximal involvement of contiguous vertebral bodies of disease as long as the index lesion(s) can be treated with RFA/PVA and fewer than 2 sites need to undergo treatment in total. Patients must have a Zubrod performance status of 0–3 and can have other sites of visceral or osseous metastatic disease. Patients with epidural extension of disease are eligible for this study provided that there is ≥ 3-mm distance between the spinal cord and the edge of the metastasis. Key ineligibility criteria include metastatic disease from radiosensitive histologies , those with frank spinal cord compression, or those with rapid neurologic decline or bony retropulsion necessitating urgent neurosurgical intervention.The primary endpoint for this trial is pain response, defined as complete or partial pain relief, as measured using the NRPS at 3 months (post-treatment pain score of 0 or at least 3 NRPS points). The NRPS is a widely utilized assessment of pain intensity in oncologic clinics and has demonstrated reliability in studies of small sample sizes and in settings where repeated measurements are obtained to monitor changes in pain intensity over time . Using tSecondary pain response endpoints include the rapidity of pain response, as defined as the time from study entry to complete or partial pain relief, and duration of pain response, as defined as the time from complete or partial pain relief to pain worsening (≥ 3 NRPS points). To assess these outcomes, patients will complete the NRPS for each treatment site at the baseline clinic visit (on the day of treatment) and daily at home with weekly measurements at 1, 2, and 3 weeks after randomization in addition to a diary of their pain medication use and any side effects they experience related to the treatment. One month after treatment, patients will complete the NRPS, and at the clinic visit, the research team will consolidate the patients’ pain level scores, pain medications, and document adverse events. Imaging of the treated spine will be obtained at baseline and at 3, 6, 12, and 24 months after randomization to assess the response to treatment as well as subacute or long-term change of the vertebral bone.The study hypothesis is that given the potential benefit of combined modality treatment in providing rapid and durable pain relief, QOL will improve after RFA/PVA and EBRT. Therefore, a number of QOL outcomes will also be prospectively collected in this study, including QOL, as measured by the Functional Assessment of Cancer Therapy (FACT-G) ; patientAll patients enrolled onto this clinical trial will receive EBRT Fig. . CT simuPatients randomized to RFA/PVA will undergo the procedure under moderate sedation in the angiographic suite or with monitored anesthesia care in the operating room. RFA/PVA will be performed with the patient in the prone position. Unipedicular or bipedicular approaches will be used depending on the anatomy and location of the metastatic spine disease. During the procedure, 10-G trocar needles will be placed via a transpedicular or parapedicular approach, and once positioned, RFA will be performed. All RFA procedures will be performed with the OsteoCool™ RF Ablation System (Medtronic Inc.) through the trocar needles. This consists of a coaxial, bipolar technology which delivers RF energy to the site of spine disease. The internally cooled ablation probes control the temperature which helps to keep RF heating within the desired treatment area and reduces the potential thermal damage to the adjacent tissue. Two probes may be used simultaneously, depending on the anatomy, to achieve larger ablation zones, and time adjustments can be made to control the size of the ablation zone. Once the RFA procedure has completed, PVA will be performed, as necessary, using 11-G needles advanced through the trocars and into the anterior 1/3 of the vertebral body. Kyphon high viscosity bone cement will be administered until the cement adequately fills the vertebral body/ablation zone or until the cement leakage precludes additional filling of the vertebral body. Kyphoplasty balloon augmentation will be performed at the discretion of the operator prior to cement administration. Once the entire procedure is completed, the patient will be transferred to the recovery area for a minimum of 3 h to allow the bone cement to solidify. Patients will be discharged the same or next day.MCI provides an in-house Clinical Scientific Review Committee (CSRC). The CSRC is responsible for reviewing all diagnostic, therapeutic, and non-therapeutic cancer research studies conducted at MCI. The MCI Data Safety and Monitoring Committee (DSMC) is responsible for assessing study progress, the reporting of adverse events and unanticipated problems, and the accuracy and integrity of the research data and protocol compliance. The DSMC is composed of representative physician experts and meets requirements as set forth from the NIH. This study will be reviewed by the MCI DSMC, independent from the investigator and study funder, every 3 months as per the assigned risk score. Both committees collaborate to ensure that the clinical trial is being conducted in regulatory compliance.MCI studies are each assigned one or more Clinical Research Coordinators (CRCs) and Research Assistants (RAs) based on therapeutic area. CRCs are responsible to assist the PIs in the scheduling of patients and collection of study-related data from patients (surveys/questionnaires). RAs are responsible for data entry into MCI’s electronic data capture (EDC) system. MCI Data Management Coordinators (DMCs) are responsible for creating electronic Case Report Forms (eCRFs) for research study. RAs enter data into these eCRFs, which is then validated. At interim and/or final analysis, MCI DMCs export the study dataset and provide it to the PI and MCI Biostatistician for data analysis.Data will be entered into MCI’s electronic data capture (EDC) system (21 CFR Part 11 compliant), which is a secured system used to collect and manage data for clinical research studies. This system is currently in use for MCI institutional studies. Patients will be identified by initials only ; if there is no middle initial, a hyphen will be used (first-last). Last names with apostrophes will be identified by the first letter of the last name. Data collected during the course of research will be kept strictly confidential and only accessed by members of the study team. Other staff employed by BHSF (sponsor) may have access to study participant data as part of their routine job duties. All staff are governed by the BHSF confidentiality policy and HIPAA guidelines.α = 0.05 and β = 0.20 and a study design of 2:1 randomization scheme (RT plus PVA/RFA:RT), the study will be adequately powered with 52 patients (35 in the RT plus PVA/RFA arm and 17 in the RT arm). Assuming a 5% ineligibility rate, a death rate of 15%, and a patient non-compliance rate of 15%, the total sample size required would be 80 patients. No interim analyses with treatment efficacy results are planned. The primary endpoint is complete or partial pain response at 3 months after randomization, and all eligible, randomized patients will be included in the analysis regardless of treatment compliance . Descriptive statistics of the actual change scores, mean change scores, and standard deviations will also be reported. For analysis of the secondary pain response endpoints (rapidity of pain response and duration of pain response), the median time to each outcome variable will be estimated using the Kaplan-Meier approach, the stratified log-rank test will be used to test for statistically significant differences with an α = 0.025, and the Cox proportional hazards regression model will be used to determine hazard ratios and 95% confidence intervals for the treatment differences. Moreover, unadjusted ratios and adjusted ratios for radiosensitive vs. radioresistant histology will be computed. The incidence of adverse events will be reported according to CTCAE v5.0, and differences in the rates at 3 months between the two treatment arms will be tested using the two-sided chi-square test at the 0.05 significance level. To analyze differences in QOL, global pain, and health utility, changes in FACT-G, BPI, and EQ-5D will be described with longitudinal data analysis. The mean differences will be compared across the treatment arms using the two sample t test at the 0.025 significance level. The relationship between treatment response and QOL will also be analyzed using the two sample t test at the 0.025 significance level.Based on the reported incidence of complete or partial pain response from the results of the feasibility matched cohort study of RFA/PVA and EBRT , with a The study protocol and patient informed consent documents were submitted to the Institutional Review Board at Baptist Health South Florida and approval was granted in 3/2020 (#1544454-2). As both treatment arms in this trial are currently approved in the routine care of patients with spine metastasis, insurance approval for the study treatment will be obtained from patients’ insurance providers. Interim reports with descriptive statistics will be prepared twice a year until the final study results are available. In general, the interim reports will contain information about the accrual rate with a projected completion date for the accrual phase, data quality, compliance rate of the treatment, and frequencies and severity of the adverse events. Unexpected adverse events (AEs) will be graded by the treating physician, assigned an attribution, and then reported to the principal investigator and study sponsor depending on grade and attribution using CTCAE v5.0. The interim reports will not contain treatment efficacy results with respect to the primary or secondary endpoints.Spine metastasis is a common occurrence in patients with metastatic disease and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life, and reduction in ability to receive cancer-directed therapies. To date, there have been more than 20 randomized controlled trials, 32 prospective non-randomized studies, and 4 meta-analyses/pooled analyses regarding the role of palliative EBRT for patients with bone metastasis . DespiteVersion 3.0 of the protocol, revised last on April 7, 2020, received IRB approval on April 19, 2020. The study is currently open to patient accrual as of May 2020, and the accrual period is expected to last 18 months. Protocol amendments, if needed, will be reviewed by the study sponsor and submitted the IRB.Additional file 1. SPIRIT 2013 Statement: Defined Standard Protocol Items.


This randomized, parallel, single-blind controlled trial study was performed on 75 ICU patients. Patients were allocated into three groups  by the minimization method. Swedish massage was provided for the patients in experimental groups (each foot for 5 minutes) once a day for six days. The pain was examined in all three groups before, immediately, and one week after the intervention. P < 0.05). Although significant difference was found in the mean scores of pain between the massage provided by a nurse and that provided by the patient's family immediately after the intervention (P < 0.05), it was not significant one week after the intervention (P > 0.05).  The mean scores of pain in the groups of foot massage by the patient's family and by a nurse showed a significant reduction at the end of the study . The control group had significantly more pain after the intervention than the family-based massage group and the nurse-based massage group ( Using foot massage, by both nurses and family members can reduce the pain of ICU patients. This intervention may improve the nursing care quality with the least cost and complications. Pain is an unpleasant sensory, emotional, and mental experience after real or potential tissue damage , 2. PainAlthough pain activates a large number of pathophysiological mechanisms in the ICU patients, the rate of pain assessment in the ICU is low . Rose etIn recent years, complementary medicines have been widely considered accompanying the standard treatment. Massage therapy, a type of complementary medicine, stimulates the nerves, tactile receptors and sends nervous impulses to the brain . MassageDifferent studies assessed the effect of massage on pain-relieving in the ICU patients. The results showed the effect of different types of massage therapies on pain relief of the ICU patients , 24–26. Regarding the importance of evaluating and controlling pain in intensive care units and considering the destructive effects of sedatives and narcotics, complementary medicines can alleviate the pain of these patients . Nurses This randomized, parallel, single-blind controlled trial has been conducted in the ICUs of Shahid Bahonar hospital in Kerman in 2017. Shahid Bahonar hospital, a trauma ICU center in southeastern Iran, has three trauma intensive care units and 46 beds.The samples were selected using consecutive sampling method, and they were allocated into three groups (two groups of intervention and one control group) by stratified randomization method. The patients were allocated to each group after being checked in terms of sex and addiction history and then by drawing dice. This process continued until the end of sampling. The first author enrolled the participants and assigned them to the three groups. The inclusion criteria were as follows: patients who were supposed to be in the ICUs at least for two weeks, patients with tracheal tube or tracheostomy , discontThe data-gathering tool in this study was the sociodemographic and clinical information questionnaire and behavioral pain scale (BPS). The sociodemographic and clinical information questionnaire included age, sex, marital status, occupation, level of education, history of admission to intensive care units, history of other illnesses, history of addiction, history of smoking, history of seizure, history of hypertension, duration of stay in the ICU, history of surgery during hospitalization, type of disease, and vital signs. BPS was used to assess pain. Payen et al. developed BPS in 2001. The scale has three items: facial appearance, status of upper limbs, and ventilator compatibility. Dehghani et al. investigated the validity and reliability of the scale. These results showed that the scores of behavioral pain scale were significantly different during painful and nonpainful procedures. Also, Cronbach's alpha was 85 for painful procedures and 76 for nonpainful procedures . YaghoubThe researcher went to Shahid Bahonar hospital in Kerman and obtained informed consent from the patient's family after receiving the code of ethics and the clinical trial registration code as well as coordinating with the head of the hospital and the authorities of the intensive care units. The coresearcher received sufficient training and measured the pain variable in three groups before the massage without being aware of the samples assignment. A physiotherapist trained the first researcher (ICU nurse) how to massage. In the intervention groups, in addition to routine care, a nurse or a family member of the patients performed Swedish massage on their feet (from knee to toes) for six consecutive days for 10 minutes (5 minutes for each foot). The massage procedure was as follows: first, the patient was placed in a supine position with a pillow under the feet so that the feet were bent slightly and the head was at an angle of 30–45 degrees. The massage area was uncovered from 10 cm above the patient's knee. Then, the researcher (the nurse) began to massage after examining the feet for the presence of the massage barriers. The Swedish massage included stroking, effleurage, vibrations, or kneading. Baby oil was used to make the area slippery and easy-to-massage (about 1-2 cc per foot), and it had no other therapeutic value. The massage was performed at 15–17o'clock when the workload of the intensive care unit was low. A napkin was used to remove the residual oil on the patient's body. The first researcher, who was a nurse of the intensive care unit, performed all massages. In addition, she trained one or two family members of the patient how to massage, and they initiated the intervention after her confirmation. The control group only received routine care. The pain was reexamined in all three groups immediately (sixth day) and one week after the intervention (thirteenth day). A coresearcher, who was not aware of the patients' assignment, assessed all measurements.Data were analyzed by SPSS 18. Descriptive statistics  were used to describe patients' demographic characteristics and clinical information. Mean and standard deviation were used to describe the pain score. Chi-squared test, Fisher's exact test, Kruskal–Wallis test, and ANOVA were used to examine the similarity of the three groups regarding the study variables. Regarding the establishment of parametric conditions , the two-way factorial ANOVA test was used to compare the pain score before, immediately, and one week after the intervention within and between the three groups. The post hoc test of Bonferroni used for multiple comparisons.Kerman University of Medical Sciences approved the study protocol (No. ir.kmu.rec.1396.1460). The study protocol was registered to the Iran RCT center (No. IRCT201707317844N12). The researcher obtained informed consent from the patient's guardian.P=0.42). Sixty percent (n = 15) of the samples were men. Sixty-eight percent (n = 17) of the samples in the family-based massage group, 76% (n = 19) of the samples in the nurse-based massage group, and 84% (n = 21) of the samples in the control group were married (P=0.42: χ2 = 1.75). In addition, no statistically significant difference was found among the three groups in occupation (P=0.96) and education levels (P=0.24). No differences were observed in the medical history among the three groups . Eighty-four percent of the samples in the family-based massage group, 88% in the nurse-based massage group, 92% in the control group had the tracheal tube, and the rest had a tracheostomy (P=0.90). No statistically significant difference was found among the three groups in the rate of spontaneous breathing (P=0.49), the rate of assisted spontaneous breathing (P=0.59), the rate of inspired oxygen (P=0.37), and the positive end-expiratory pressure (P=0.90). The administration of narcotics  and nonnarcotics  was not significantly different among the three groups before the intervention (P > 0.05). In addition, no significant differences were found among the three groups in the mean arterial blood pressure (P=0.28), heart rate (P=0.08), and arterial blood saturation (P=0.61) at the beginning of the study.The level of consciousness was nine in all three groups based on the Glasgow coma scale. The length of stay in the ICU was five to six days in all three groups before the study . Few studies compared the effect of massage performed by the family and a nurse on pain of the ICU patients . JamaatiSeveral studies have examined the effect of massage by the family or a nurse on pain of the ICU patients. Najafi et al. showed a reduced pain intensity in patients undergoing coronary artery bypass graft surgery after being massaged by the their family caregivers . CutshalThe results of the present study and available evidence suggest that massage by trained nurses or family members of patient can reduce the pain of ICU patients. Therefore, considering the importance of family-centered care, nurses' workload, and shortage, families can provide massage, and involving families in massages can lead to effective interventions after patients' discharge from the hospital. However, nurses should train patients and their families properly , 41. In One of the limitations of this study was the lack of cooperation of some families. No information about the disease and the effect of massage on the patient and difficulty to attend in the hospital for six consecutive days were the causes of this limitation. This limitation was eliminated by training the family and reducing their concerns as well as by contacting with families who were not present at a proper time. In addition, two family members who provided the massages might influence the results. However, only seven cases were massaged by two family members (3-4 sessions with one family member and 1-2 sessions with another member). As the majority of the sessions were provided with the same family members, the data were analyzed on a per-protocol basis and not an intention to treat. The study samples did not represent all patients in the intensive care unit, so the results could not be generalized to other patients admitted to the intensive care unit. In addition, the first researcher allocated the samples into groups, which may be associated with bias.According to the results of this study, our hypothesis is approved. On the other hand, the mean scores of pain was significantly different among the family-based massage group, the nurse-base massage group, and the control group after the intervention. The mean pain scores in the family-based massage group and the nurse-based massage group significantly decreased after the intervention, but the mean pain score in the control group did not significantly decrease after the intervention. Massage, an easy and low-cost method, is helpful for pain reduction in unconscious patients admitted to the intensive care units. Regarding the importance of pain control in patients admitted to the intensive care units and considering few studies in the field of complementary medicine and massage therapy on patients admitted to ICU, researchers interested in the field of complementary medicine are recommended to do studies with a larger sample size in different environments and research communities. Further studies are recommended to clarify the effect of massage therapy on other symptoms of unconscious patients admitted to the intensive care units, including agitation, delirium, and intensive care unit-acquired weakness.


There was little difference with the aligners group  . The technique used influences the pain and quality of life of patients at the start of orthodontic treatment.The aim of this study was to compare pain and its relationship with the oral quality of life of patients with different types of orthodontic appliances: conventional and conventional low-friction brackets, lingual brackets, and aligners. A prospective clinical study was carried out with a sample size of 120 patients  divided into 4 groups of 30 patients each. The modified McGill questionnaire was used to measure pain at 4, 8, and 24 h and 2, 3, 4, 5, 6, and 7 days after the start of treatment, and the Oral Health Impact Profile-14 (OHIP-14) questionnaire was used to measure the oral-health-related quality of life (OHRQoL) in the first month of treatment. The maximum peak of pain was obtained between 24 and 48 h of treatment. It was found that patients in the lingual orthodontic group described lower levels of pain at all times analyzed, and their scores in the total OHIP-14 indicated less impact on their oral quality of life (1.3 ± 1.2,  Regarding orthodontic treatment, around 90% of patients state that pain and discomfort are the main drawbacks . When faDuring orthodontic treatment, different forces are applied through the brackets and arches that cause tooth movement in the alveolar bone . PatientPain is a subjective response, showing great individual variation. It depends on factors such as individual threshold, magnitude of applied force, emotional/stress status, cultural differences, and previous pain experiences . RegardiTherefore, the pain that patients experience and the discomfort associated with orthodontic treatment will negatively influence the quality of a patient’s oral life ,14,15. OAccording to most authors, self-ligating brackets produce less pain and have less impact on the oral quality of life than conventional fixed orthodontic treatment ,13,17,18In this study, we evaluated how four different types of orthodontic appliances affected dental pain and its intensity during the first week and the impact on quality of life during the first month of treatment. The null hypotheses were as follows: There is no significant difference in pain and OHRQoL in orthodontic patients with conventional, low-friction, and lingual brackets and aligners. The alternate hypotheses were as follows: There is a significant difference in pain and OHRQoL in orthodontic patients with conventional, low-friction, and lingual brackets and aligners.The research project was approved by the Bioethics Committee of the University of Salamanca (USAL_16/060). A prospective one-month follow-up clinical study was performed after the placement of four different orthodontic appliances: conventional, low-friction, and lingual brackets and orthodontic aligners . The guidelines established by the Declaration of Helsinki for research on humans were followed. Prior to participation in the study, patients were told that participation was voluntary, and the treatment protocol was explained to them. Furthermore, they were asked for their written consent.Sample size was calculated using Raosoft’s online sample size calculator . Using a 5% margin of error and a 95% confidence level, the target sample size was determined to be 120 patients, including a 10% dropout.®, 3M, Rogers, Arkansas, USA). The second group (Low friction—LF) was treated with conventional low-friction brackets . The third group  wore multibracket fixed lingual brackets . The slot dimension of the brackets described above was 0.018" × 0.025" in bracket groups. Finally, the fourth group  used an aligner system , following Invisalign’s own treatment initiation protocol. The arches used were a Cooper NiTI arch of 0.014" in the CON and LF groups and a universal preform Cooper NiTI arch of 0.013" with individual 0.10 in. metal wires in the LO group, in accordance with the STB® technique protocol described by Dr. Scuzzo [This one-month prospective clinical study was performed on a total sample of 120 patients , divided into four groups of 30 individuals each. This sample size was similar to that used in other previously published studies ,24. The Patients between 18 and 40 years of age and with permanent dentition;Without previous orthodontic treatment;No previous extractions except third molars;Dental bone discrepancy between –2 and –6 mm in both arches;Good oral health without caries or periodontal disease;Skeletal class I or mild classes II and III (ANB 0°–5°) .The inclusion criteria were as follows:Patients with deciduous teeth or in the process of dental replacement;Patients in need of orthodontic surgical treatment or dental extractions due to treatment;Patients with systemic diseases;Patients with medication that influences pain perception ;Severe malformations;Anatomy of the lingual side that would prevent lingual brackets being cemented in the lingual orthodontic group.Before starting the study, we performed a periodontal evaluation. All patients began the study in good oral health.The exclusion criteria were as follows:After the placement of the appliances, the patients were given a visual analog scale (VAS) based on the McGill modified questionnaire to reflect the pain suffered and another to analyze their quality of life ,28. BefoPain intensity was measured using VAS with values ranging from 0 (no pain) to 10 (maximum pain) on a 10 cm long line with different points in time after starting orthodontic treatment: 4 h (T4h), 8 h (T8h), 24 h (T1), 2 days (T2), 3 days (T3), 4 days (T4), 5 days (T5), 6 days (T6), 7 days (T7), and from the 7th day (T18) ,30.Furthermore, after the first month of treatment, the patients had to complete the Oral Health Impact Profile-14 (OHIP-14) questionnaire to analyze the level of impact on their oral quality of life ,32. The The total impact on quality of life was calculated as the sum of the items, the frequency level of which was occasional or more frequent in order to obtain a pure, quantitatively derived variable  that reflected each patient’s global well-being. This same strategy was used to compute the impact on each of the 7 domains of the OHIP , each consisting of two items.F-test was used. If it was statistically significant, a comparison between groups was made using the Bonferroni post hoc test. The Chi Square test was performed to compare two or more nominal or ordinal distributions. A p-value of less than 0.05 (p < 0.05) was established to declare a difference as statistically significant, and a p-value of less than 0.01 (p < 0.01) was used to consider the result highly significant. In addition, we considered the results with p-values between 0.06 and 0.10 as tending toward statistical significance. SPSS v. 20 software  was used to analyze the data.To describe the studied population, the mean and standard deviation were used as quantitative variables, and the sampling distribution (number of patients and the corresponding percentage) was determined for the nominal and ordinal data. To compare the groups with respect to quantitative variables, the ANOVA The mean age of the sample was 30.0 ± 7.5 years. Of the 120 patients, 66 were women (55%) and 54 were men (45%). The degree of crowding was measured as the skeletal discrepancy prior to treatment; no statistically significant differences were observed .p < 0.01) in the pain level were found at 4 h after treatment according to the VAS scale. The group with the most pain at this time point was the conventional bracket group (3.8 ± 2.3), with similar results to the Invisalign group (2.8 ± 2.5), and the lingual bracket group had the least pain (1.7 ± 2.5) next to the low-friction group (2.0 ± 1.9). After 48 h and also with a p < 0.01, a higher level of pain was observed in low-friction patients (5.8 ± 1.9), without differences with the conventional group, while those with lingual brackets continued to show the lowest level of pain (2.7 ± 2.1). This trend continued until T7 , with the low-friction bracket group presenting the highest level of pain  and the lingual bracket group presenting the least pain (4 ± 1.9 and 0.04 ± 0.2). However, after 8 h of treatment, a value of p = 0.06 was achieved, a value that is almost statistically significant, with greater pain occurring in the conventional group (4.7 ± 2.3) and less pain occurring in the lingual bracket group (3.3 ± 1.9)  .The maximum pain peak was reached 24 h after the start of treatment in the conventional (5.0 ± 2.7), lingual (4 ± 1.9), and Invisalign (4.4 ± 2.1) groups and at 48 h in the low-friction group (5.8 ± 1.9). After this time, the pain began to decrease gradually .p < 0.01) and physical disability  in the conventional group, with the lingual group having the smallest impact on pain (0.8 ± 0.8) and the Invisalign group having the lowest effect on physical disability (0.03 ± 0.2). There were no differences with the low-friction group in both categories.When we analyzed the impact on the quality of life domains in relation to oral health , we obsep < 0.01), psychological disability , and social disability , as well as for the total impact scores . The values found in the Invisalign group in these dimensions were similar with respect to the lingual group , at 3 days with the Invisalign group , and at 4 days with the low-friction group  . In the In comparative studies between conventional and Invisalign appliances, it was observed that the pain in patients who underwent the two techniques was similar during the first two days of treatment and greater in conventional treatments from the third to the fourth days ,47. Our Other authors observed that Invisalign (first 24 h) and lingual (after 2 days of treatment) patients were associated with more dental pain compared with conventional orthodontic treatment . These rAccording to the literature published in recent years, there does not appear to be a statistically significant difference in pain with the different arches analyzed ,48,49 orSeveral questionnaires have been used to assess the oral quality of life in orthodontic patients. In this study, the OHIP-14 questionnaire was chosen because it is the most widely used in the consulted literature and is easy to complete by patients ,33,51. IF: 16; gl: 3; p-value: 0.00)  .Classically, it has been considered that, due to the morphology and placement of the brackets, lingual appliances lead to greater pain and discomfort for the patients, negatively influencing their oral quality of life  ,44,53. LIn our analysis, we observed lower impact values for all quality-of-life domains in the lingual bracket group . We did The differences found in other studies ,55 may bOne of the limitations when conducting this study was the achievement of a homogeneous sample with respect to sex or age, since most patients who choose more aesthetic techniques  or who choose to receive orthodontic treatment in general are women and adults. In the literature, we found that sex does not influence pain perceived by adult patients and that age influences the perceived pain to a greater extent in adolescents and not in adults ,12,13. ITo the best of our knowledge, this is the first study to compare four different orthodontic techniques. Our main objective was to analyze pain and the influences of different orthodontic techniques on improving the oral health and quality of life of our patients during treatment. In the future, we intend to expand the number of participants in the sample, equalize the percentage of women and men, and include other types of orthodontic appliances for comparison.The maximum peak of pain was reached between the first 24 h  and 48 h (low friction) after treatment, and then, it decreased to near zero at the end of the first week of orthodontic treatment. Lingual bracket patients presented the lowest level of pain at all time points and had the least negative impact, with statistically significant differences in terms of pain, psychological discomfort, psychological disability, social disability, and total OHIP-14 scores. The results obtained in this study showed a slightly higher quality of life in patients using aligners than in lingual patients, with no large discrepancies between groups. However, there were great differences between the conventional and low-friction groups.Based on the results of this study, we reject the null hypothesis and accept the alternate hypothesis that there is significant difference in pain and OHRQoL in orthodontic patients with conventional, low-friction, and lingual brackets and aligners.