This study aimed to compare the effects of cognitive functional therapy (CFT) and movement system impairment (MSI)-based treatment on pain intensity, disability, Kinesiophobia, and gait kinetics in patients with chronic non-specific low back pain (CNSLBP).In a single-blind randomized clinical trial, we randomly assigned 91 patients with CNSLBP into CFT (n = 45) and MSI-based treatment (n = 46) groups. An 8-week training intervention was given to both groups. The researchers measured the primary outcome, which was pain intensity , and the secondary outcomes, including disability (Oswestry disability index), Kinesiophobia , and vertical ground reaction force (VGRF) parameters at self-selected and faster speed (Force distributor treadmill). We evaluated patients at baseline, at the end of the 8-week intervention (post-treatment), and six months after the first treatment. We used mixed-model ANOVA to evaluate the effects of the interaction between time (baseline vs. post-treatment vs. six-month follow-up) and group (CFT vs. MSI-based treatment) on each measure.CFT showed superiority over MSI-based treatment in reducing pain intensity  = 2.41), ODI , and Kinesiophobia  at eight weeks. The CFT also produced greater improvement in VGRF parameters, at both self-selected , and faster speed, FPF, WAR, POR] than the MSI, except SPF at eight weeks.This study suggests that the CFT is associated with better results in clinical and cognitive characteristics than the MSI-based treatment for CNSLBP, and the researchers maintained the treatment effects at six-month follow-up. Also, This study achieved better improvements in gait kinetics in CFT. CTF seems to be an appropriate and applicable treatment in clinical setting.https://www.umin.ac.jp/ with identifier number (UMIN000047455).The researchers retrospectively registered the trial 10/11/2022, at The online version contains supplementary material available at 10.1186/s12891-023-06815-x. Low back pain (LBP) affects people around the world at a high occurrence rate . ChronicOne important impairment in patients with LBP is related to the walking task. Pain, kinesiophobia, and effort to reduce pain by restricting spinal movement cause changes in gait parameters such as decreased step length and step speed, along with widened step width in patients with chronic LBP . The infCurrent management of chronic LBP includes a range of different treatments –9. Over A movement-based strategy, uniquely designed for each patient, suggests that the MSI-based treatment approach improves the accuracy of spinal movements and induces specific changes in the musculoskeletal system, such as altering movement patterns and promoting painless movement patterns , 15. In On the other hand, CFT is a novel approach that not only cover postural and movement behaviors, but also consists of two other components includes biopsychosocial understanding of pain, and lifestyle change . To addrAccording to the above-mentioned statements, this RCT aimed to compare the MSI-based treatment with the CFT approach on pain intensity, disability, Kinesiophobia, and gait kinetics in patients with CNSLBP. We hypothesized that CFT could improve pain, disability, and Kinesiophobia, while MSI-based treatment seemed more influential for gait kinetics.https://www.umin.ac.jp/ with identifier number (UMIN000047455).This was a 2-arm RCT, parallel-group study with blind outcomes assessor, conducted from September 2018 to August 2019 in the corrective exercises center of the Kharazmi University, Tehran, Iran. The trial was retrospective registered 10/11/2022, at The researchers measured pain intensity as the primary outcome using the Numeric Ratings Scale (NRS) and assessed changes in disability, Kinesiophobia, and VGRF parameters as secondary outcomes with the Oswestry Disability Index (ODI), Tampa Kinesiophobia Scale (TKI), and (Force distributor treadmill), respectively, a week before the interventions. After assessing demographic data and outcome measures, the researchers randomly assigned patients to receive either CFT or MSI-based treatment.The biomechanics laboratory of the Sport Sciences Research Institute conducted baseline, post-treatment, and follow-up assessments. A well-experienced assessor assessed the outcomes at the baseline, the end of the 8-week training period (post-treatment), and the end of the six-month follow-up in the same place. The patients did not receive any treatment, including physiotherapy and exercise, between the post-treatment and the six-month follow-up. The supervised clinical sessions in the corrective exercises center of the university also performed the treatments.The patients complained LBP were recruited through flyers in the physical therapy clinics, occupational health services, and primary care practices. Based on the inclusion criteria, the researchers enrolled eligible patients to participate in the study.https://icd.who.int/)), classified by the duration of pain for more than 12 weeks (Non-specific LBP) [This study included patients with LBP  and overIf the researchers found neurological disorders, spinal pathologies, structural deformity, osteoporosis, inflammatory disorder , radicular syndrome, history of tumor and fracture in the spine, true leg length discrepancy more than 20 mm, or BMI greater than 30 kg/m2, they excluded the patients.Based on previous studies, researchers calculated that they should enroll at least 40 subjects per each group to complete the study if they used an α error of 0.05, standard deviation of 2.5, and a power of 0.8 , 22. Thehttp://randomizer.org. The researcher arranged the allocation sequence using a blocked randomization model with a block size of 4 and concealed it in numbered, sealed, opaque envelopes. Just before the first treatment session, the treating clinicians opened the envelope to reveal the group allocation.A researcher with no involvement in the trial conducted randomization based on a computer-generated random sequencing  using the website The researchers measured pain intensity using a numerical rating scale (0–10), where 0 signified no pain, and 10 represented the worst unbearable pain. The patients rated their current level of pain intensity using this scale. The numeric rating scale version used to measure pain intensity has not been cross-culturally adapted for the Persian-speaking population with low back pain. Although the NRS is a widely accepted and validated tool for evaluating self-reported pain intensity in various populations . ResearcThis study used the Persian translated Oswestry Disability Index to assess disability in patients with low back pain. It is important to note that the researchers cross-culturally adapted the Oswestry Disability Index version for Persian-speaking patients with LBP in this study . This adOne study used the Persian translation of Tampa Scale for Kinesiophobia to evaluate kinesiophobia. This specific version has been cross-culturally adapted for the Iranian patients with chronic persistent pain . This coBased on the study of da Fonseca et al. (2009) we assessed VGRF parameters . After iFirst (FPF) and second Peak Force (SPF): the first and second maximum peak of VGRF during the stance phase in straight walking after the heel contact. Mid-Support Force (MSF): the minimum peak of VGRF between the first and second peak forces. Weight Acceptance Rate (WAR): the magnitude of the first peak force divided by the time at which it occurred. Push-Off Rate (POR): the magnitude of the second peak force divided by the time from the second peak force until the end of the stance phase .The movement system impairment-based treatment group received 11 sessions of MSI-based treatment over the 8 weeks for 60 min per session with a supervision of a native speaker experienced above 5 years) physical therapist with the knowledge of MSI-based treatment . The res years phCognitive functional therapy was prescribed for each patient in CFT group based the CFT protocol conducted by O’Sullivan et al. 2015) , 33. Pat5 , 33. PA statistician performed statistical analyses, using SPSS version 16.0 . The Kolmogorov-Smirnov and Levene tests were used to check the normal distribution of variables and homogeneity of variance, respectively. We used mixed-model ANOVA to evaluate the effects of the interaction between time (baseline vs. post-treatment vs. 6-month follow-up) and group (CFT vs. MSI) on each measure. We used Bonferroni correction to assess changes in each group across the three-time points. For each variable, we calculated the percentage of change compared with baseline. We also conducted intention-to-treat analyses for all randomized patients, including those who dropped out. Cohen’s d was used to calculate effect sizes (ES), which were classified as small (d < 0.20), medium (d = 0.21–0.79), or large (d > 0.80) .The CONSORT 2010 guidelines display the flow diagram of this trial in Fig. F = 117.29, p < 0.001), ODI  and TSK . Between groups analysis showed significant differences at 8-weeks post-intervention  also the values were significantly lower in NRS, ODI and TSK in the CFT group. At 6-months follow-up there was a statistically significant difference , where the values were significantly lower in NRS, ODI and TSK in the CFT group . These results suggest that the CFT protocol was more effective than MSI in reducing pain intensity, disability, and kinesiophobia. The mean of changes in for NRS, ODI, and TSK in both group were more than MCIDs, except for ODI in the follow up. However, in the group of CFT, thses changes were higher as follow: NRS , ODI , and TSK .Table self−selected speed, SPF self−selected speed, MSF self−selected speed, WAR self−selected speed, POR self−selected speed, FPF faster speed, WAR faster speed, and POR faster speed showed significant group × time interaction effects. Bonferroni post hoc analysis showed higher scores in the CFT group on the GRF parameters at self-selected speed and GRF parameters at faster speed at 8 weeks’ post-intervention, and 6 months follow-up. No statistically significant interaction between interventions was.Table The CFT and MSI treatment groups did not report any adverse events during the eight-week training, and the assessments in the pre-test, post-test, and 6-month follow-up did not record any adverse events.This study aimed to compare efficacy of CFT and MSI-based treatment on pain, disability, kinesiophobia, and gait kinetics in CNSLBP patients. Evaluation of functional status revealed superiority of CFT approach on reduction in pain intensity, disability, and kinesiophobia through an 8-week intervention and six months follow up over MSI-based treatment.According to the bio-psycho-physiological improvement in recent years, it is time for health-care practitioners to shift their perspective away from a biomedical model, toward prescribing the treatment for CNSLBP based on a multidimensional classification-based approach with the aim of making the treatment more self-centered and focusing on cognitive-behavioral aspects rather than the signs and symptoms associated with the disorder.According to O’Sullivan’s classification, two sensitizations found LBP, including central sensitization affected by psychological and cognitive factors, and peripheral sensitization connected to impairments in movement and controlling movement . CFT in Activity avoidance is related to fear, which reflects the belief that activity may result in (re)injury or increased pain as a result of dysfunctional interpretations of pain and injury that can be adaptive in the acute pain stage but contradictorily worsen the problem in the case of chronic pain . The useTo support our results, Vibe Fersum et al. (2013)  stated tAfter 8 weeks of treatment with both interventions, the evaluation of gait kinetics in people with CNSLBP showed significant improvements in VGRF parameters such as FPF, SPF, MSF, WAR, and POR from baseline. However, the CFT approach appeared to be more effective than the MSI-based treatment. The results showed that, the POR and WAR increased in the self-selected speed in both treatment groups. It means that the time to reach heel-contact and return time from push off have decreased . Thus, iAt the self-selected and fastest walking speeds, WAR and POR increased in the CFT group more than in the MSI group, representing increased speed and decreased time in reaching the FPF peak and returning from the SPF peak. FPF and SPF both increased at the fastest walking speeds in both intervention groups. Generally, more improvement in MSF was observed in the CFT group. To the best of our knowledge, this is the first trial assessing the effects of CFT and MSI-based treatment on gait kinetics in patients with CNSLBP. Our results clearly showed that impaired gait in CNSLBP patients improved more in the CFT group than in the MSI group.Previously, Barzilay et al. (2016)  found thTo support Barzilay’s study findings, we found the improvement of VGRF parameters with the improvement of pain, disability, and kinesiophobia. In CFT group we saw significant percentage of changes for pain (60.74%), disability (52.98%), and kinesiophonbia (44.6%) accompanied with the better improvement of VGRF parameters after prescribing eight-week multidimensional intervention. Also, significant percentage of changes for pain (44.23%), disability (50.15%), kinesiophonbia (36.73%) and improvement of VGRF parameters observed in CFT group six months after the first treatment.According to Krekoukias et.al , LBP patIn this study patients in both experimental groups preferred to walk faster in post-test in both self-selected speed and faster speed, besides the push-off rate improved in both groups specially in CFT group. Therefore, it is likely cognitive functional therapy improved the dealing with perturbations and as a result progressed the push-off rate and gait speed.Patients with low back pain, showing higher electromyographic activity of the rectus abdominis and erector spinae during gait . Also, bIn contrast to the physiological gait, the pelvis rotates in the opposite direction from the trunk, but low back pain patients demonstrated gait compensations that exhibit increased pelvic rotation with concurrent trunk rotation which is assumed for antalgic purposes .In this study, the CFT group showed better pain improvement compared to the MSI group, which may result in a greater reduction of these compensatory movements. The CFT group has demonstrated more progression in gait parameters.Other aspects include the influence doctors have on patient outcomes and treatment confirmation, including their communication skills, empathy and degree of trust . Along wsimilar to our previous hypothesis, we can draw a conclusion that when patients received both psychological- and movement-based treatment that educated patients how to move better in their daily-routines, overcome their fear and change their beliefs toward a self-control management, they can perform better their functional tasks like walking with less fear of movement.This study has some limitations First, to better evaluate gait performance, researchers propose including not only VGRF but also the horizontal ground reaction forces. Second, the current study is limited by the lack of electromyography (EMG) in recording the functioning of core and abdominal muscles. Third, future studies should examine CFT intervention with other therapeutic methods, as it is currently compared with MSI treatment in this study. Fourth, this study based its sampling strategy on patients with chronic low back pain, which is defined as pain lasting for 90 days or more. Although the researchers selected pain intensity as the primary outcome measure, it should be noted that experts often recommend studies of patients with chronic pain to prioritize the primary outcome of disability, as pain intensity is more susceptible to regression to the mean. Despite using validated measurement tools and baseline assessments to minimize this potential limitation, the decision to make pain intensity the primary outcome may influence the overall interpretation of treatment efficacy. Finally, the lack of a translated and validated Persian version of Central Sensitization Inventory prevented us from assessing central sensitization. If we had used this tool, we could have determined whether there was any association between pain improvement and central sensitization in the studied population. For future similar studies, a translated and validated version of the Persian Central Sensitization Inventory will be beneficial, in addition to other pain intensity measures. For future studies, authors also suggest that random forest analysis with the Shapley Additive Explanations (SHAP) summary plot can present useful information regarding the rankings of major predictors and the directions of their associations with the superior effects of cognitive functional therapy.The main implication of the current findings is that, in addition to changing lifestyle and functional training, fostering a biopsychosocial understanding of pain and cognitive training are helpful for maximizing efficiency of treatment in patients with non-specific chronic LBP. The current data suggest that both CFT and MSI-based treatment seem to have beneficial effects on rehabilitation of CNSLBP patients through reduction of pain, disability, and fear-avoidance behaviors, and improvement of VGRF parameters. The CFT approach produces better outcomes, which may be due to its multidimensional therapeutic effect. Of course, the results of this study need to be confirmed with a larger number of patients.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2


There are several invasive dental procedures that require local anesthetics. However, its infiltration is usually associated with anxiety and fear, increasing the perception of pain in pediatric patients. For this reason, it is important to evaluate different strategies for its application. We compared the anesthetic effect of the administration of 2% lidocaine with epinephrine 1:80000 non-alkalized at slow speed and alkalized at fast speed to block the inferior alveolar nerve in deciduous molars.  A crossover clinical trial was carried out whose sample consisted of 38 patients between 6-10 years who required bilateral pulp treatment in their first mandibular primary molars. At the first appointment, they received 2% lidocaine with 1:80000 alkalinized epinephrine administered at a fast rate, and at the second appointment, 2% lidocaine with 1:80000 non-alkalized epinephrine administered at a low speed. We evaluated the onset of action, duration of the anesthetic effect, and intensity of pain during its infiltration.  We found that non-alkalized lidocaine at slow speed had a shorter onset time of action (57.21±22.21 seconds) and longer duration of effect (170.82±43.75 minutes) compared to administration of alkalinized lidocaine at fast speed . There was no difference in the level of pain intensity.  In this study, the slow administration of the non-alkalized local anesthetic showed a shorter onset time of action and a longer duration of the anesthetic effect in comparison with the alkalized local anesthetic administered at a rapid rate in the blockade of the inferior alveolar nerve in deciduous molars. This pain in turn produces anxiety in children and parents, which frequently leads to non-compliance with visits to the pediatric dentist.Local anesthetics prevent pain impulse conduction during several invasive dental procedures, such as pulp treatments, extractions, etc. However, the infiltration of these drugs produces pain, and its perception is greater in pediatric patients.Regarding the mechanism of action of local anesthetics, they come in two forms: ionized and non-ionized. The non-ionized form, due to its liposolubility, easily crosses the neuronal membrane and concentrates in the cytosol, where it is ionized to block sodium channels. By blocking sodium channels, the perception and conduction of pain are prevented. Therefore, the action of local anesthetics depends on the amount of the ionized form; and this, in turn, is related to their dissociation potential (pKa).The pKa is the pH at which the local anesthetic is 50% ionized and 50% non-ionized. The pKa of local anesthetics varies between 7.9 and 8.9. In addition, the pain caused by the application of local anesthetics with vasoconstrictor could be greater because they have a lower pKa. For this reason, several strategies have been proposed to reduce pain during the administration of local anesthetics, including slow-speed application and alkalinization. Alkalinization consists of adding a buffer to the local anesthetic, increasing its pKa, and approaching tissue pH (7.4). This could decrease the pain during the application, reduce onset time and increase the duration of action of local anesthetics. A recent systematic review by Tirupathi et al reported that pain scores were lower in children who were administered the alkalinized local anesthetic by blocking the inferior dental nerve. Nonetheless, the current evidence is limited, and quality studies are needed to evaluate the efficacy of this intervention.In inflammatory and infectious processes, the medium acidifies, which decreases the non-ionized form’s formation, reducing the efficacy of the local anesthetic. The study aimed to compare the anesthetic effect of the administration of lidocaine 2% with epinephrine 1:80 000 non-alkalinized at a slow speed and alkalinized at a fast speed for the blockade of the inferior dental nerve in deciduous molars.Based on this, considering that the administration of local anesthetics  is a necessary procedure to perform several dental treatments in pediatric patients. An experimental, longitudinal, prospective study was conducted. The sample consisted of 33 patients aged 6 to 10 years ASA I (American Society of Anesthesiologists category 1) who required pulp treatment and were enrolled from August to October 2019 in the Pediatric Dentistry Service of the Hospital Nacional Arzobispo Loayza (HNAL). On the other hand, mothers who accepted their children’s participation in the study signed an informed consent form and their children signed the informed assent.The CONSORT guidelines for randomized clinical trials were followed for the reporting of the research. The study was approved by the ethics committee of the Faculty of Medicine of the Universidad Nacional Mayor de San Marcos (19-0058) and the Hospital Nacional Arzobispo Loayza (HNAL: 112-2019). In addition, the study was conducted under The International Conference on Harmonization Good Clinical Practice guideline (ICH-GCP).https://www.sergas.es) for the difference of means of paired groups. We considered a mean difference to detect of 0.55 and a standard deviation of differences of 0.73 with a statistical power of 80% and a significance level of 5%. The sample size was 32 patients, therefore a sample size of 33 patients was considered in our study.For the calculation of the sample size, we used Epidat v4.2 software . In which the pediatric patient had to choose one of the envelopes indicating the treatment assigned for the first appointment . Then on the second appointment, the other treatment was administered . Moreover, both the patient and the parent were unaware of the type of technique administered . All local anesthetic administrations were performed by a single operator. After pulp treatment, all patients have prescribed ibuprofen suspension at a dose of 20mg/kg every 8 hours (100 mg/5 mL) after the anesthetic effect had ended. was followed in which 0.18 mL of the anesthetic solution was extracted from the cartridge with a tuberculin syringe and that volume was discarded. Then 0.18 mL of an ampoule of 8.4% sodium bicarbonate was loaded and added to the cartridge. Subsequently, the solution was slowly shaken 20 times and once the preparation was finished, the anesthetic was immediately administered with a cartridge syringe.For alkalinization of lidocaine 2% with adrenaline 1:80 000 with sodium bicarbonate, the technique performed by Saatchi et al The administration of the alkalized local anesthetic was carried out at a rapid speed in a period of 15 seconds, marking the cartridge in 3 segments of 17 mm each and each segment was administered in 5 seconds controlled by a stopwatch. The administration of the non-alkalized local anesthetic was carried out at a slow speed for a period of 60 seconds, for this, the cartridge was marked in 6 segments of 8.5 mm each and each segment was administered in 10 seconds controlled by a stopwatch. The onset of action of the local anesthetic was recorded by the elapsed time in seconds. From the administration of the local anesthetic until the patient presented a tingling sensation on the tip of the tongue and/or lower hemilabium on the side where the administration of the local anesthetic. To evaluate the duration of the anesthetic effect, the parent or guardian of the child was asked to remain in the waiting room so that the researcher could register the duration of the anesthetic effect. This duration of the anesthetic effect was registered by the time elapsed in minutes. From the onset of action until the disappearance of the numbness sensation of the tip of the tongue and/or lower hemilabium on the side of the administration of the local anesthetic. this scale presents adequate validity and reliability for the evaluation of pain in pediatric patients. This scale consists of a numerical vertical line (from 0 to 10) and six faces with different expressions of pain. In which an increasing discomfort is shown from a face without pain to an image in which the maximum expression of pain appears. The children registered on the card the intensity of pain they perceived during the inoculation of the anesthetic solution. All patients were fitted with glass ionomer as a final restoration.For the evaluation of pain intensity, the Wong-Baker Scale known as the verbal graphic scale was used. According to the systematic review by Stinson et al, Stata software version 16.0 was used for statistical analysis. Numerical variables were expressed as a mean and standard deviation; categorical variables were expressed as absolute and relative frequencies. In addition, the intention-to-treat analysis was performed considering the last measurement registered. For the evaluation of categorical variables, the chi-square test was used. For numerical variables, the Student’s t-test for paired samples was used. Considering a significance level of 5% to reject the two-tailed null hypothesis. Of the 47 patients who met the eligibility criteria, 14 patients were excluded. Of the total 33 patients included, 17 were male and 16 were female with a mean age of 7.09 ± 1.48 years. Patients’ mandibular first molars were randomized to the alkalinized lidocaine group administered at a fast speed (n = 33) and the non-alkalinized lidocaine group administered at a slow speed (n = 33).In the follow-up, three patients did not attend their second appointment. Therefore, a total of 63 injections were administered using the inferior dental nerve block technique. The flow diagram of the participants is presented in P = 0.021; Non-alkalinized lidocaine administration at a slow speed produced a shorter time to onset of action (57.21 ± 22.21 seconds [95% CI: 52.63 to 63.79]) compared to alkalinized lidocaine administration at a fast speed (74.03 ± 22.09 seconds [95% CI: 68.60 to 79.46])  compared to administration of alkalinized lidocaine at fast speed (148.24 ± 36.24 minutes [95% CI: 139.33 to 157.14]) . These results differ from those reported by Chumpitaz-Cerrate et al who found that the time to onset of action was shorter in the alkalinized lidocaine group (105.72 ± 9.7 seconds) compared to the non-alkalinized lidocaine group (157.52 ± 12.1 seconds) (P = 0.002). Nonetheless, the study by Hobeich et al found that the time to onset of action was similar in patients who were administered 5% alkalinized lidocaine (116 ± 68 seconds), 10% (121 ± 59 seconds); and those who were administered non-alkalinized lidocaine (119 ± 68 seconds) in healthy maxillary canines. These differences could be due to variations in methodology and participant characteristics. Regarding the former, different ways of assessing the onset of anesthesia such as electrical pulp testing and palpation were used. In addition, the studies had different designs such as parallel and crossover randomized clinical trials. On the other hand, different administration times and anesthetic techniques were used. Hobeich et al used the infiltration technique to anesthetize the upper teeth; this makes a difference because the cortex in the mandible is thicker, denser, and has less porosity in comparison with the maxillary bone.It was found that the administration of lidocaine not alkalinized and administered at a slow speed (57.21 ± 22.21 seconds) presented a shorter onset of action time, compared to the administration of lidocaine alkalinized and administered at a fast speed (74.03 ± 22.09 seconds)  in pediatric patients was 86 ± 27.8 seconds, while for alkalinized lidocaine it was 84.2 ± 28.9 seconds (P = 0.824). On the other hand, Kurien et al conducted a study on a pediatric population aged 6 to 12 years, who required bilateral pulp therapy in primary mandibular molars. They found that rapid administrations (30 to 40 seconds) of alkalinized and preheated anesthetics had a shorter time to onset of action (130 seconds) compared to anesthetics administered at a slow speed (60 seconds).Other studies such as that of Chopra et al using a dilution of 1:10). In addition, the pain was assessed every 15 seconds with gingival probing. Unlike our study, it was assessed with the appearance of a tingling sensation in the tongue and lower lip.These differences compared to our study could be because different concentrations of adrenaline (lidocaine 2% with epinephrine 1:200 000) and sodium bicarbonate were used to alkalinize the anesthetic solutionP < 0.05). Similarly, Kurien et al found that fast-speed (30 to 40 seconds) administrations of alkalinized anesthetic and preheated anesthetic (30 to 40 seconds) presented a shorter duration of effect, compared to slow administration of anesthetic (60 seconds) (P < 0.001). This could be because the anesthetic solution when administered at a slow speed, allows the solution to remain in contact with the nerve fibers for a longer time. This would lead to an increase in the duration of the time effect of the local anesthetic. On the other hand, Chumpitaz-Cerrate et al reported that the duration of effect was similar between the administration of alkalinized (194.44 ± 8.5 minutes) and non-alkalinized (205.4 ± 11.6 minutes) lidocaine in adult patients. These reported differences may be due to the clinical characteristics of the participants and the different alkalinization methods.It was found that the administration of non-alkalinized lidocaine at a slow speed (170.82 ± 43.75 minutes) presented a longer duration of anesthetic effect, compared to the administration of alkalinized lidocaine at a fast speed (148.24 ± 36.24 minutes)  presented similar pain to the administration of non-alkalinized lidocaine (23.5 ± 19.1). Schellenberg et al found that, in adult patients with symptomatic irreversible pulpitis in lower premolars or molars, non-alkalinized 4% lidocaine with epinephrine 1:100 000 had similar anesthetic success as alkalinized lidocaine (40% [95% CI: 26.4-54.9]) and 32% [95% CI: 19.5-46.7], respectively. Success was defined as no or mild pain (VAS ≤ 54 mm) during root canal access or instrumentation. Chopra et al performed a randomized crossover clinical trial and found that alkalinized solution did not reduce pain from infiltration. In addition, Baker et al conducted a randomized crossover clinical trial in 25 children (10 to 12 years) and found that there was no difference in infiltration pain, the onset of action, and duration of anesthetic between the group administered alkalinized and non-alkalinized anesthetic solutions.Previous studies have reported that the application of alkalinized local anesthetic reduces injection pain during its application compared to non-alkalinized local anesthetic. In medicine, the alkalinization of local anesthetics has been widely used to achieve greater success in dental anesthesia. The local anesthetic solution has an acidic nature, which can produce pain during infiltration and delay the onset of anesthesia. found that fast-speed (30 to 40 seconds) administrations of alkalinized anesthetic and preheated anesthetic (30 to 40 seconds) produced less pain intensity during local anesthetic injection compared to anesthetic administered at slow speed (60 seconds) (P < 0.001). Similarly, systematic reviews such as Hanna et al reported that alkalinized local anesthetics reduced pain (Mean difference: -1.17 [95% CI: -1.68 to -0.67]) during their administration compared to non-alkalinized local anesthetics. In addition, Tirupathi et al found that alkalinized local anesthetic reduced pain perception compared to non-alkalinized local anesthetic (Mean difference: -0.32 [95% CI: -0.55 to -0.09]). Similarly, Kattan et al reported that alkalinized local anesthetics improved the success of anesthesia  compared with non-alkalinized local anesthetics (OR: 2.29 [95% CI: 1.11 to 4.71]).On the other hand, Kurien et al This variability in results is due to high methodological heterogeneity  and clinical heterogeneity .This study had some limitations; first, pain perception is subjective and may vary among patients; however, a validated scale for pain assessment in pediatric patients, such as the Wong-Baker visual analog scale, was used. According to our study, the slow administration of lidocaine 2% with non-alkalinized epinephrine 1:80 000 has a shorter time to onset of action and longer duration of anesthetic effect compared to the rapid administration of lidocaine 2% with alkalinized epinephrine 1:80 000 in lower dental nerve block in deciduous molars. However, injection pain was similar between both study groups. We are grateful to the patients who participated in the study and contributed substantially to the research. There is no conflict of interest among all authors. The original certificates issued by the Institutional Research Ethics Committee of the Hospital Nacional Arzobispo Loayza and the Research Ethics Committee of the Department of Medicine of the Universidad Nacional Mayor de San Marcos are presented. Self-financed.


Pain associated with head and neck cancer (HNC) is difficult to manage and reduces quality of life. It has been increasingly recognized that HNC patients exhibit a wide range of pain symptoms. Here we developed an orofacial pain assessment questionnaire and conducted a pilot study to improve pain phenotyping in HNC patients at the diagnosis. The questionnaire captures the following pain characteristics: pain intensity, location, quality, duration, and frequency; the impact of pain on daily activities; changes in smell and food sensitivities. Twenty-five HNC patients completed the questionnaire. 88% patients reported pain at the site of tumor; 36% reported multiple pain sites. All patients with pain reported at least one neuropathic pain (NP) descriptor, 54.5% reported at least two NP descriptors. The most common descriptors were “burning” and “pins and needles”. Most patients reported increased pain to sour or hot/spicy food/drinks, and to food with coarse/hard textures. Patients exhibited impaired oral function, especially chewing, talking, mouth/jaw opening, and eating. Tumor progression has a significant impact on pain. Nodal metastasis is linked to pain at multiple body sites. Patients with advanced tumor staging experience greater pain at the primary tumor site, when exposed to hot or spicy food/drinks or food with hard/coarse texture, or when eating or chewing. We conclude that HNC patients experience a wide range of pain symptoms with altered mechanical, chemical, and temperature sensation. Improved phenotyping and stratification of pain in HNC patients will help address the underlying etiology, which may enable personalized therapeutic approaches in the future. Chronic pain resulted from cancer or cancer treatments such as surgery, radiation, and chemotherapies or in combination, is particularly challenging as patients suffer from multiple oral complications such as orofacial pain, changes in taste, and oral dysfunction , 2. Thesi.e., referred pain), some experience pain at multiple locations. For the first time, we report that a subset of HNC patients develop increased pain sensitivities to sour and hot/spicy food as well as food with hard/coarse texture, suggesting chemical, thermal, and mechanical hypersensitivities at the oral cavity. There was a strong correlation between nodal metastasis and referred pain. Patients with advanced tumor staging experience greater pain at the primary tumor site, when exposed to hot or spicy food/drinks or food with hard/coarse texture, or when eating or chewing. Pain intensity at the tumor site has a significant impact on the total sensory scores as well as the total function scores. The next step is to refine the questionnaire and validate our study in a bigger cohort.In this pilot study, we designed a simple orofacial pain questionnaire (OFPQ) with the aim to simultaneously capture pain quality, intensity, and frequency at each painful body site, spontaneous pain as well as evoked pain, the extent of pain affecting daily function/activities, and finally, the sensory and taste disturbance in the oral cavity due to the disease. We found that as reported previously, HNC patients experience both spontaneous and evoked oral pain at the site of tumor –6. Surpr2.2.1.The validated UCSF oral cancer pain questionnaire (UCSFOCPQ) has been used extensively to characterize intensity, sharpness, and aching nature of spontaneous and evoked pain, touch sensitivities, as well as oral function as a result of pain , 7 focus2.2.A single-center, prospective study was carried out to assess orofacial pain in patients with HNC. The study was conducted from July 2021 to July 2022. The study complied with the guidelines for human studies and was conducted in accordance with the “World Medical Association Declaration of Helsinki”. The study was approved by the Committee of Ethics for Research Human Studies of the Sao Paulo State University (UNESP), School of Dentistry, Araçatuba, Sao Paulo, Brazil and informed consent was obtained from all participants. Only de-identified information was shared for data analysis. Twenty-five patients with histology proven head and neck squamous cell carcinoma (HNSCC) who referred for oncological treatment at the Oral Oncology Center, UNESP, School of Dentistry, Araçatuba, São Paulo, Brazil, were enrolled in this study. Inclusion criteria were patients over 18 years of age; histopathological diagnosis of HNSCC; and primary tumor located in the oral cavity, oropharynx, or larynx. Exclusion criteria were patients reporting preexisting pain related with other non-oncological diseases; with previous oncological treatment; or inability to answer the orofacial neuropathic pain questionnaire. A healthcare professional explained each questionnaire items to patients and all patients were interviewed before starting cancer treatment.2.3.Prism 9 was used to perform the statistical analyses. Standard parametric  or nonparametric  tests were used, depending on normality. Chi-square or Fisher's exact test was used to determine the difference in distribution between groups. Results were presented as mean ± standard deviation (SD), mean ± standard error of the mean (SEM), or mean (range), wherever appropriate. Significance level was set at *P < 0.05, **P < 0.01, ***P < 0.001.GraphPad 3.3.1.n = 12; 48% and stage III–IV n = 13; 52%). 9 (36%) patients had neck nodal invasion. None of the patients had remote metastasis.A total of 25 HNSCC patients with an age range of 42–78 years (mean = 61.6 years) completed the questionnaire at the diagnosis visit. Demographic data of the entire patient cohort are shown in 3.2.n = 2), numbness (n = 1), itching (n = 1), pinching (n = 1), shooting (n = 1) are not common among the 22 patients who reported pain. For patients who reported “burning” and “pins and needles”, most patients experience them on daily basis (Twenty-two (88%) HNC patients reported pain at the site of tumor. Eight of them (36%) reported pain in other orofacial pain regions in addition to the site of tumor, with a mean of 4 sites per patient . The sitly basis . Six pat3.3.n = 14), to spicy/hot food or drinks (n = 13), and pain to food with coarse/hard textures (n = 11) more than usual , mouth/jaw opening (n = 12), talking (n = 13), eating (n = 12), and to a lesser degree drinking , compared to those with early-stage (I and II) . Similar4.The purpose of this pilot to study is to determine whether we can capture thermal and chemical hypersensitivities, referred pain, as well as pain quality that are suggestive of neuropathic nature, which are not commonly included in existing orofacial pain questionnaires. Orofacial pain is unique in that the orofacial region not only has rich blood and nerve innervation in a confined space, but it also involves multiple specialized organs such as mouth, tongue, lips, tooth, jaw that serve critical functions such as eating, talking, drinking, which have significantly impact on patients' social life and nutritional status. Orofacial pain associated with HNC and its treatment such as surgery, chemotherapy, and or radiotherapy reduce quality of life and survival. It has been increasingly recognized that pre-existing pain condition could influence pain following cancer treatment, especially pre-existing NP which is more distressing than nociceptive pain, with a greater impact on life and health , 11. TheThe major finding of the study is that orofacial pain associated with HNC is heterogeneous; patients exhibit a combination of symptoms that are unique to them. This new OFPQ validated results from UCSFOCPQ that spontaneous and evoked pain is prevalent in HNC patients at the site of the tumor, which limits oral function. However, a subset of HNC patients exhibit a wide range of symptoms, such as referred pain, burning pain, pins and needles, and pain sensitivities to food at the cancer diagnosis. Patients may describe their pain as pins and needles at one location and stabbing at a different body location. The frequency and duration for different pain subtypes also varies dramatically among patients. The heterogeneity of the pain may reflect differences in anatomy, pathophysiology, and socio-psychological factors among patients.The most interesting finding is that HNC patients report to have increased pain sensitivities to hot/spicy and sour food as well as food with hard/coarse texture. While mechanical allodynia of the tongue has been reported extensively, chemical, heat, or cold-induced pain are rarely assessed in HNC patients , 15. A r+, ATP  and the Pittsburgh Sleep Quality Indenx (PSQI) to investigate symptoms of anxiety and depression and sleep disturbance in HNC patients. These questionnaires can be used in conjunction with the OFPQ to factor in pain-associated comorbidities. As a pilot study, the questionnaire specificity and reliability were not tested as we expect further refinement of the questionnaire may be needed. Lastly, our sample size is very small which is not sufficiently powered to answer a few important questions related to HNC pain. For example, although our study agrees with known epidemiology that HNC affects men three times more than women , our stuIn summary, this pilot study identified diverse pain features that are unique to patients with HNC. Improved phenotyping and stratification before treatment provide opportunities for a better understanding of etiology underlying post-treatment oral complications, which may enable personalized therapeutic approaches in the future.


The ESPB group used less fentanyl during the initial 24 h after surgery (P = 0.004) and experienced less pain  than the control group. The time to the first ambulation and the length of hospital stay were shorter in the ESPB group than in the control group . In conclusion, ESPB could promote early recovery by reducing opioid consumption and pain intensity in patients receiving LCS.Various techniques have been formulated to reduce pain and ensure early recovery after surgery, as these are major concerns among surgeons, anesthesiologists, and patients. Erector spinae plane block (ESPB), the injection of local anesthetic into the fascial plane, is a simple and novel analgesia technique widely used due to its minimal risk of complications. ESPB has been tried in various surgeries; however, no study has reported its use in colorectal surgery. This study investigated whether ESPB could promote early recovery following laparoscopic colorectal surgery (LCS) by reducing opioid consumption and pain intensity. After randomization into the ESPB or control groups, an ultrasound-guided ESPB was performed at the thoracic 10 Effective postoperative pain control without adverse effects of analgesic medications is the essential objective of ERAS pathways4. Recent studies have focused on the multimodal approaches for opioid-sparing analgesia, which uses opioids sparingly to reduce opioid-related complications, including nausea, vomiting, sedation, and respiratory depression5.Surgeons, anesthesiologists, and patients have been most concerned about pain and early recovery after surgery. Various efforts have been introduced to help patients recover early after surgery, and the Enhanced Recovery After Surgery (ERAS) protocol is the most comprehensive strategy for these efforts. ERAS regimens have been increasingly used to maintain physiological function, accelerate recovery, and reduce postoperative stress after surgeries7. Nevertheless, many patients continue to suffer from pain after LCS, which may impede recovery or rehabilitation9. Therefore, reducing pain after surgery has been considered important for the rapid recovery of patients, and for this purpose, various regional anesthesia techniques have served as an important component of multimodal anesthesia11.Laparoscopic colorectal surgery (LCS) is related to reduced postoperative pain, analgesic requirements, lower morbidity, faster recovery, and shorter length of hospitalization than open surgery14. However, in contrast to the paravertebral block which is technically challenging, time-consuming, and has a substantial risk of complications, ESPB is a fascial plane block that utilizes simple sonographic landmarks and carries a low risk of serious complications16.Among various regional anesthesia techniques, the erector spinae plane block (ESPB) is a simple and novel analgesia technique widely used for its minimal risks. By injecting local anesthetics into the fascial plane, ESPB has the similar mechanism action with the paravertebral block; local anesthetics are distributed to multiple levels of paravertebral space, providing visceral and somatic analgesia in the thoracoabdominal region12, it is now increasingly used as a perioperative analgesic method in various surgeries18. Because the erector spinae muscles extend over the cervical, thoracic, and lumbar regions, and the local anesthetics used for ESPB spread both cranially and caudally over a wide range of dermatomes 12, when carried out at low thoracic levels, this technique can provide analgesia to the lower abdomen, which is essential for colorectal surgeries17. Previous clinical studies have focused on ESPB for thoracic surgery or upper abdominal surgery, such as laparoscopic cholecystectomy21. Nevertheless, controlled clinical data on the effects of ESPB on the postoperative recovery of patients who underwent lower abdominal surgery are insufficient.Although ESPB was initially used to treat severe neuropathic painFrom these backgrounds, the current study aimed to determine the efficacy of ESPB in LCS. We hypothesized that ESPB provides significant analgesic effects, decreases postoperative opioid consumption, and facilitates postoperative recovery.http://www.umin.ac.jp; registration No. UMIN000041455; registration date: August 18, 2020). All study participants were informed of this study before surgery and written informed consents were obtained. All the methods employed in this study were performed in accordance with the guidelines stipulated in the Declaration of Helsinki. We complied with the requirements established by the Consolidated Standards of Reporting Trials (CONSORT).This is a double-blind, prospective randomized controlled trial. The institutional review board of Seoul National University Bundang Hospital approved this study (No. B-1907-553-002). The study protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry  physical status of class I or II were included in this study. Patients in whom needle insertion and bupivacaine injection could cause significant complications, including those with a history of allergic reaction to local anesthetics, serum creatinine level of > 2.0 mg/dL, coagulation abnormality, platelet count of < 50,000/mmwww.randomizer.org). Each patient was asked to select an envelope before entering the operating room. Based on the random number, each patient was assigned to either the ESPB or the control group  before surgery.An independent researcher prepared 64 identical opaque envelopes for randomization, each containing a random number from 1 to 64. Each number in the envelope was linked to the group allocation number generated by the randomization program  was placed parasagittally lateral to the spinous process between Thoracic 10th and 11th level to identify the erector spinae (ES) muscle and the adjacent transverse process. A 22-guage needle was inserted craniocaudally in plane to the transducer through the ES muscle to position the needle-tip near the corresponding transverse process and intertransverse muscles. Thereafter, 2–3 mL of 0.9% saline was injected to determine the appropriate needle position and to detach the ES muscle from the transverse process. Following the confirmation of correct needle position and absence of intravascular puncture, 20 mL of 0.25% bupivacaine at each side  was injected to the patients in the ESPB group. After the injection, the same procedure was repeated on the contralateral side. For the patients in the control group, an identical procedure, except for the injection of 0.9% normal saline instead of 0.25% bupivacaine, was performed. Because the injected drug was prepared before the intervention without group information, patients and the independent anesthesiologist who performed the ESPB had no knowledge of the group designation.After the ESPB procedure, the patient’s vital signs were monitored in the supine position using electrocardiography, non-invasive blood pressure measurement, pulse oximetry, and capnography. Then, general anesthesia induction was initiated with 1.2–1.5 mg/kg of propofol and 0.6 mg/kg of rocuronium after denitrogenation with 100% oxygen. After confirming adequate muscle relaxation with train-of-four stimuli, tracheal intubation was performed . General anesthesia was maintained with 2–3 vol% of sevoflurane and a target-controlled infusion of remifentanil to maintain hemodynamic stability. Laparoscopic surgical methods, including incision size and location and number of ports, were standardized according to the type of surgery at the Seoul National University Bundang Hospital. At the end of the surgery, neuromuscular blockade was reversed with 0.01 mg/kg of glycopyrrolate and 0.04 mg/kg of neostigmine. The patients were extubated when the train-of-four ratio exceeded 90% and spontaneous breathing was established.®, Ewha Biomedics, Seoul, Korea) containing 15 µg/mL of fentanyl solution was applied to each patient. The PCA was implemented under the following protocol: continuous basal infusion rate of 1 mL/hour, a bolus dose of 1 mL, and a lock-out time of 15 min. At 1, 6, 12, and 24 h after LCS, a blinded researcher assessed pain severity when coughing using a 100-mm visual analog scale . When the pain score was > 30, intravenous rescue analgesics  were administered.When the surgery was completed, an intravenous patient-controlled analgesia device  requiring antiemetic medication during the first 24 postoperative hours were also collected.The number of participants required for this trial was estimated using G*power version 3.1.9.6 . In the pilot study, the amount of fentanyl required during the first 24 postoperative hours in patients who received LCS was 685.5 ± 220.7 (mean ± standard deviation) µg. Assuming that the standard deviation of the two groups is the same and a 25% reduction in fentanyl consumption in the ESPB group is clinically significant, the required number of participants was calculated to be 32 per group under the condition of alpha = 0.05, beta = 0.2, and an assumed dropout rate of 10%.P-values less than 0.05 was considered statistically significant, and all reported P values were from two-sided tests.NCSS 2021 Statistical Software version 21.0.4  was used for statistical analyses. After checking the normality of the data with the Shapiro–Wilk test, we used the Mann–Whitney U test for the comparison of the continuous variables, and the chi-square test (or Fisher’s exact test) for comparing the categorical variables. Continuous variables were expressed as median with interquartile range, while categorical variables as frequency with percentage. Among the 64 eligible patients, a total of 57 patients  completed the protocol. The CONSORT diagram is illustrated in Fig. The demographic data of the patients are presented in Table P = 0.004; Table P < 0.05, Fig. The total fentanyl requirement during the first 24 postoperative hours was significantly less in the ESPB group than that in the control group  and long-term opioid dependency, which is significantly associated with the global opioid crisisnt Table . This mi23. Further, it is associated with less pulmonary complications and better functional mobility at discharge1, and it may reduce the length of hospitalization, thereby decreasing healthcare costs24. Prolonged bed rest may lead to thromboembolic complications and even insulin resistance25. Therefore, most ERAS guidelines strongly recommend early postoperative ambulation26. However, severe postoperative pain is the most common barrier preventing early mobilization after surgery. As shown in this study, optimal pain management is needed to facilitate mobilization after surgery26. Thus, ESPB can be considered an effective ERAS component for LCS.Early ambulation after colorectal surgery is essential for ERAS as it counteracts the negative physiological consequences of surgical stress27. Since ESPB decreased pain in the acute phase, it may reduce the likelihood of developing chronic persistent pain after LCS. Further research is needed to confirm the long-term effect of ESPB after surgery.Ultrasound-guided ESPB in our protocol significantly reduced the postoperative pain score at every time point. In colorectal surgery, pain intensity during the first 24 after surgery is significantly correlated with the occurrence of chronic pain three to six months after surgery28. Cadaveric studies also found that local anesthetic spread resulted in blockade of rami communicants as well as ventral and dorsal rami, thereby demonstrating the potential mechanism of visceral blockade29. Thus, with respect to the postoperative period of colorectal surgery, ESPB may be superior to other regional blocks that merely provide somatic analgesia31.The analgesic effect of ESPB on visceral pain remains controversial; however, several recent clinical studies have provided supporting evidence for visceral pain relief by ESPB32. However, it may be insufficient in some surgeries as it only addresses somatic pain33. Another such plane block is quadratus lumborum block, which covers the thoracolumbar fascia and the paravertebral space and is considered an effective plane block for colorectal surgery as it relieves visceral pain as well as somatic pain34. However, quadratus lumborum block is relatively invasive, technically challenging to perform, and is associated with risk of hypotension or motor weakness36. EPB, on the other hand, is a relatively simple procedure with a minimal risk of complications because the target is easily visualized and vulnerable structures are far from the target37. In our study, there was no case of complication and no case where the procedure was difficult to perform.Other fascial plane blocks are also performed to reduce postoperative pain in colorectal surgery. One such plane block is the transversus abdominis plane block, a simple and popular anesthetic method for abdominal surgeryThis study may have some potential drawbacks. First, we did not determine the sensory blockade after ESPB. Determining whether the skin sensations are blocked may reveal group allocation to the physicians and patients, thereby breaking the blinding. Instead, we visually observed by ultrasound that the local anesthetics were well distributed in the target area, thereby confirming that ESPB was adequately performed. Second, the study did not include other regional blocking techniques to compare their analgesic effects. Instead, because patients in the control group received a sham block, the differences in fentanyl consumption and postoperative pain between the two groups can reflect the pain-alleviating effect of pure ESPB itself. Further research is required to explore and compare the analgesic effects of different regional anesthetic procedures (including ESPB) in colorectal surgery. Finally, the current study was performed in a single university-affiliated hospital; consequently, this may limit the generalization of the results. Furthermore, our hospital does not have an active multimodal approach to reducing perioperative opioid use. Thus, clinical data on the effects of ESPB in various perioperative settings should be investigated.In conclusion, ultrasound-guided ESPB significantly decreased fentanyl requirement and pain after LCS. This procedure also facilitated early ambulation and shortened the length of hospitalization in patients who underwent LCS. Our findings suggest that ESPB could be a powerful approach for ERAS protocols.


Shoulder disorders occasionally cause intractable pain. Central sensitization (CS) may be involved in such pain. Identifying risk factors associated with CS is crucial for effective pain control. This study aimed to determine the effects of shoulder osteoarthritis and rotator cuff tears (RCT) on CS and associated factors. This study included patients evaluated for CS using the Central Sensitization Inventory (CSI) before surgery for shoulder osteoarthritis, RCT, or cuff tear arthropathy. Patients with a CSI score of 40 or higher were defined as having CS. The relationships between glenohumeral osteoarthritis (GHOA), RCT size, and CS were statistically analyzed. Multiple regression analysis was performed to examine the factors affecting CSI scores. Subjects included 167 patients: 131 patients had RCT without GHOA, 23 had GHOA with RCT, and 13 had GHOA without RCT. The GHOA group had a significantly higher CSI score (27.5 [10.8–40.5] vs. 18.0 [10.0–27.5]) and CS prevalence (27.8% vs. 8.4%) than the RCT without GHOA group. There was no significant correlation between RCT size and CSI scores. Multiple regression analysis showed that female sex, severe pain, and long pain duration were associated with higher CSI scores. Considering the risk factors for CS might be helpful in shoulder treatment. The pathophysiology of shoulder pain due to shoulder diseases is diverse and includes tendonitis, rotator cuff tears, and osteoarthritis . HoweverAlthough there are some reports on central sensitization of the shoulder ,24,25, tBased on previous studies implicating central sensitization in other musculoskeletal diseases ,17,18,19This retrospective cross-sectional study included patients who underwent unilateral shoulder surgery between January 2020 and January 2022 for rotator cuff tears, cuff tear arthropathy, or shoulder OA. A Japanese version of the CSI record was obtained preoperatively to assess CS. Patients who had received preoperative drug treatments for CS, such as tramadol, duloxetine, and pregabalin, were excluded. Details of this study protocol are shown in CS was evaluated using Part A of the Japanese version of the CSI, and a total score of 40 or higher was defined as CS. CS severity was classified into the following five categories based on CSI scores: subclinical (0–29), mild (30–39), moderate (40–49), severe (50–59), and extreme (60–100) . To invet-test was used to compare the two groups following a normal distribution, and the Mann-Whitney U test was used for those not following a normal distribution. Categorical variables were evaluated using the chi-squared test. The association between rotator cuff tear size and CS was evaluated in the groups according to tear size using the Kruskal-Wallis test, followed by the post hoc Steel-Dwass test. Multiple linear regression analysis with the CSI score as the objective variable was performed as a multivariable analysis to identify risk factors for CS. All statistical analyses were conducted using R  with a significance level of p < 0.05. Because this was a retrospective study, sample size calculations were not performed. However, a post hoc power analysis using G*Power software , which is a statistical power analysis software tool, showed a power of 0.82 with an alpha error of 0.05 for detecting a significant difference in CSI values between patients with and without OA, a finding which is the primary outcome of this study.Results that follow a normal distribution are presented as mean ± standard deviation, and data that do not follow a normal distribution are shown as median [interquartile range]. Student’s This study included 167 patients  with a median age of 70.0 [63.0–75.0] years; 131 patients (78.4%) had rotator cuff tears without GHOA, 23 (13.8%) had GHOA with rotator cuff tears, and 13 (7.8%) had GHOA without rotator cuff tears. The patients’ demographic data are shown in detail in The median CSI score was 18.0 [10.0–32.0], and the incidence of CS with a CSI score of 40 or more was 12.6% in all patients . Moderatp = 0.043). The incidence of CS with a CSI score of 40 or higher was considerably higher in the group with GHOA (with rotator cuff tear and without rotator cuff tear) (27.8%) compared to the group without GHOA (with rotator cuff tear) (8.4%) (p = 0.004). Patients with GHOA were significantly older than those without it (p = 0.001). Patients with GHOA tended to have longer pain duration than those without GHOA, which was insignificant due to wide variability .The results of the association between GHOA and CS are shown in p = 0.004). The other patients’ backgrounds were not different between them.Furthermore, since it is necessary to assess whether the presence or absence of rotator cuff tears affects CS among patients with GHOA, we further subdivided the GHOA group by the presence or absence of rotator cuff tears to examine the effect of rotator cuff tears on central sensitization. The results regarding the effect of central sensitization with and without rotator cuff tears in GHOA patients are shown in The results of the associations between rotator cuff tears and CS are shown in Patients with large or massive tears were significantly older than those with partial-thickness and small/medium-sized tears. The other patients’ characteristics were not different between them.The results of the multiple linear regression analysis are presented in In this study, we hypothesized that patients with GHOA, especially women, are more likely to develop CS and undergo shoulder surgery. Supporting this hypothesis, patients with GHOA had significantly higher CSI scores and a higher incidence of central sensitization than those without GHOA. On the other hand, the presence or absence of rotator cuff tears in patients with GHOA did not significantly differ in the incidence of CS or CSI scores, nor did the incidence of CS or CSI scores by rotator cuff tear size without GHOA. Multivariable analysis also revealed that female sex, severe pain, and longer pain duration were independent risk factors for CS in shoulder surgery patients for shoulder OA and rotator cuff tears.In this current study on shoulder surgery, patients with rotator cuff tears and GHOA, the incidence of CS was 12.6%. The incidence of CS by disease was 8.4% in patients with rotator cuff tears without OA and 27.8% in patients with OA. CS is defined by the International Association for the Study of Pain as the “Increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input” and is a condition of increased pain sensitivity due to changes in the pain threshold , and it Regarding the effect of CS on postoperative outcomes, the clinical outcomes of TKA in patients with preoperative CS were poorer than those in patients without CS ,19. FurtThis study revealed that patients with GHOA had significantly higher CS incidence rates and CSI scores than those without GHOA. Patients with GHOA had a longer duration of pain, although the difference was not significant, with considerable variation. There was no significant difference in the CSI score according to the rotator cuff tear size. Regarding the relationship between OA and CS, patients with knee OA were more likely to experience pain sensitization than those without OA. The mechanism of CS caused by OA is related to excessive ascending nociceptive signaling and insufficient descending inhibitory signaling, which are maintained by peripheral nociceptive input from the OA joint , suggestMultivariable analysis undertaken in the current study to identify independent risk factors for CS revealed that sex, pain intensity, and duration of disease are independent factors that contribute to the CSI score. With regard to CS and sex, women are at higher risk of CS than men . In addiThis study had several limitations. First, because this was a retrospective study, data collection on patient background, including patients’ physical activity levels, lifestyle habits, and comorbidities, was limited. A previous report suggests that lifestyle factors, such as sleep deprivation, stress, diet, smoking, and physical inactivity, should be considered in understanding central sensitization . AnotherIn shoulder surgery patients for shoulder OA and rotator cuff tear, the incidence of CS occurred at 12.6% in this study. Regarding the incidence of CS by pathological conditions, 27.8% of the patients with GHOA had CS in this study, a significantly higher percentage than rotator cuff tear patients without GHOA (8.4%). Rotator cuff tear was not related to the CS incidence and CSI score in GHOA patients. Furthermore, female sex, pain intensity, and duration of pain are independent factors that contribute to high CSI scores and may be risk factors for the incidence of CS, indicating that these risk factors should be considered when treating pain due to shoulder disorders.


Estimating the contribution of endplate oedema known as Modic changes to lower back pain (LBP) has been the subject of multiple observational studies and reviews, some of which conclude that the evidence for an association of Modic change with LBP is uncertain while others demonstrate a clear link. The clinical trials demonstrating the benefit of basivertebral nerve ablation, a therapeutic intervention, in a tightly defined homogenous patient group with chronic LBP and Modic changes type 1 or type 2, provides further evidence for the contribution of Modic changes to LBP and shows that in these subjects, nerve ablation substantially reduces pain and disability. These interventional studies provide direct evidence that Modic changes can be associated with lower back pain and disability. This review set out to explore why the literature to date has been conflicting.A narrative, forensic, non-systematic literature review of selected articles to investigate why the published literature investigating the association between Modic imaging changes and chronic low back pain is inconsistent.This review found that previous systematic reviews and meta-analyses included both heterogeneous study designs and diverse patient syndromes resulting in an inconsistent association between Modic changes and nonspecific chronic lower back pain. Re-analysis of literature data focussing on more homogenous patient populations provides clearer evidence that Modic changes are associated with nonspecific chronic lower back pain and that type 1 Modic changes are more painful than type 2.Studies using tightly defined homogenous patient groups may provide the best test for association between MRI-findings and pain and disability. Clinical benefit of basivertebral nerve ablation observed in randomised controlled trials further supports the association between type 1 and type 2 Modic changes with pain and disability. The proportion of an adult population seeking hospital care for chronic lower back pain (CLBP) > 3-months) at least once has been estimated at 0.5% of the population per year . Investm-months aPatients with severe and persistent lower back pain and disability have a poor prognosis and respond poorly to conservative therapies –9. Magne. identified that there was no strong association between lumbar MRI findings and pain or disability in patients with CLBP, because of the heterogeneity of the published studies and of the clinical outcome measures used. They recommended new studies to evaluate the association of MCs with LBP and supported current guidelines restricting the imaging of patients with nonspecific CLBP [A recent systematic review and meta-analysis by Herlin et alfic CLBP .Until now, the field has been largely observational. With the observed clinical benefit in randomised controlled trials of basivertebral nerve ablation (BVNA) and its subsequent regulatory approval for the treatment of patients with MC1 and MC2 endplate oedema and vertebrogenic pain, the importance of identifying Modic changes has been recognised , 23–26. It is important to reassess past literature now that the evidence for the clinical importance of recognising MCs is clearer, to understand why observational and interventional studies might have reached different conclusions.We have conducted an independent evaluation of the analyses conducted in the Herlin et al. review in order to investigate if reducing the heterogeneity of the studies altered the strength of the association between Modic changes and chronic low back pain. In addition, we have conducted a review of the studies published since Herlin et al. We have focussed on studies exploring MRI findings and MCs and their association with CLBP and disability, in well-defined more homogenous populations of patients with nonspecific CLBP.. were inspected and assessed against the Herlin et al. inclusion/exclusion criteria [. criteria were included and the outcomes were then re-evaluated. This led to the removal of some studies which Herlin et al. included in their analysis. The methodology in source publications was inspected in detail and, where possible estimates were recalculated to reduce heterogeneity in the populations, e.g. where a publication focussed on pain associated with Modic changes type 1 (MC1) compared to non-MC1, the latter being defined as Non-Modic plus Modic changes type 2 (MC2) and Modic changes type 3 (MC3), a more meaningful comparison of MC1 versus non-Modic (MC0) was calculated. MC2 versus MC0 and MC3 versus MC0 were also calculated. All statistical calculations were performed using SAS™ 9.4 software [Articles cited in the systematic review/meta-analysis by Herlin et alcriteria . Publicasoftware . Aggrega. were identified using PubMed [Papers citing Herlin et alg PubMed , 30–49. . found that six of 13 studies reported a statistically significant association of MC1 and LBP [. and the source publications cited, focussed on studies with a homogenous and appropriate patient population. Seven of the 13 articles were not considered relevant to our study as they were investigating the interaction between MCs and the efficacy of facet joint injections [Herlin et al and LBP –55 and s and LBP , 56–61. jections , patientjections , focussejections , 55, 57 jections . One art. investigated the relationship between concordant pain on provocative discography and defined types of MCs [Five of the 13 articles selected by Herlin et als of MCs , 58, 59.s of MCs . The stus of MCs , and Tho. summarised Braithwaite et al., as a nonsignificant association, a significant association of any MC, MC2, and MC3 with pain on provocative discography was observed in this study. As the five studies were of similar design, the aggregation of the data using the CMH estimator was performed and resulted in the following results: for MC1 versus MC0, an OR of 8.34 , for MC2 versus MC0 an OR of 4.46  and for MC3 versus MC0 an OR of 3.39  was estimated for pain on provocative discography  that did not respond to conservative therapy with sufficiently severe disability to consider surgical intervention [p = 0.012) and they concluded that MC1 are associated with lumbar spinal pain with the anaesthetic injection that relieves both disc and endplate pain. The major limitation of the study was its size, as it was too small to be definitive, but the data would fit with the findings in our analysis and with the literature on BVNA.Korhonen et alrvention . The dia. in a retrospective cross-sectional observational study found that the size of MC may have more impact on pain, disability and health-related quality of life than the type of change, but the study was not large enough to allow comparison of small, medium and large MC1 and MC2 [Udby et al and MC2 .. [Dimitriou et al.  investig. .. provide a seminal review of the identification and treatment of patients with axial nonspecific low back pain with basivertebral nerve ablation [In a comprehensive editorial in Pain Medicine, Conger et alablation . Patientablation . Patientablation .., intended to only include studies of nonspecific LBP of any duration and excluded specific causes of LBP and post-surgical patients in their review. Unfortunately, the inclusion of a more heterogenous patient population than intended resulted in inconclusive results which they acknowledged. This increased heterogeneity resulted from: including publications that grouped all types of MC together; not differentiating between acute and chronic LBP; including patients with current herniation or scoliosis. Herlin et al. acknowledged that the heterogeneity of studies included was a problem but rather than reduce the heterogeneity they included all of the studies which resulted in a confounded analysis. We do recognise that having published their review protocol in Prospero they had limited freedom to do so. Unfortunately, Herlin et al. is often being inappropriately cited as demonstrating no association between LBP and MC without acknowledging its limitations [Herlin et alitations –38, but itations , 39–49.When strict criteria are used and a more homogenous patient population is evaluated, a clear association between MC1 and MC2 with pain on provocative discography and subject pain and disability can be observed –51. ThisUnderstanding the relationships between the disc, endplate, and vertebral marrow in health and disease and their relationship with pain generation, perception and disability is complex and multidisciplinary , 79. TheDisc degeneration can be initiated by endplate damage or disc herniation, leading to a cascade of inflammatory activities that result in MCs , 83, 84.With the approval of BVNA to treat vertebrogenic chronic low back pain, there is now a therapeutic intervention available to treat patients with MCs at a painful level, but it requires magnetic resonance imaging for diagnosis of vertebrogenic pain. The imaging guidelines, which currently recommend that these patients should not be imaged, will need to be reviewed in response to the changing clinical options for these patients and will almost certainly lead to an increased use of imaging for nonspecific CLBP patients.The analyses to date assume that each MC type represents a homogeneous condition and underlying disease process but even within these sub-groups there are additional factors including both biological and psychosocial factors which can influence the pain and disability experienced by patients. Modic changes can be associated with pain and disability, pain on provocative discography, and in a proportion of subjects, can be asymptomatic. What is not clear is whether the painful and asymptomatic MCs are the same. Population surveys of asymptomatic subjects can find up to 13.5% MC1 and 25.4% MC2 . In the Some limitations must be taken into consideration when interpreting the results of this study. One of the authors (LGC) works for Persica Pharmaceuticals Ltd, and two authors (OR and DM) work on a Persica sponsored clinical trial investigating an intradiscal antibiotic to treat patients with CLBP and Modic type 1 changes and therefore disclose an interest in Modic changes being associated with pain and disability and we acknowledge that this may introduce a sub-conscious bias. LGC provided the literature review and if any sub-conscious bias was introduced it would most likely be at this stage of the review process. This was not a systematic review or meta-analysis and a review protocol was not prospectively made public. This review proposes that the effects of MRI-findings on pain and disability should be studied in defined homogenous sub-groups of patients to isolate that finding and to minimise confounding causes of pain. This reductionist approach may enable MRI-findings to be investigated in specific patient groups, but the findings may not be generalisable to subjects with multiple findings and more complex disease.We conclude that Modic changes type 1 and type 2 can be painful, and that the confusing literature is due at least in part to heterogeneous study selection, inclusion of patients with a diversity of syndromes and inappropriate reporting. Patients with debilitating CLBP and Modic changes may be denied effective therapy if the current literature continues to be cited and inappropriate conclusions drawn. Basivertebral nerve ablation may be effective, but it is an invasive, irreversible procedure. Whether it becomes widely adopted or not, it provides an intervention which indicates that Modic changes type 1 and 2 do contribute to pain and disability that can be alleviated. Future alternative treatments that address the causes of Modic changes such as inflammation and infection, or the consequences of Modic changes such as bone remodelling, may find clinical utility and offer patients and physicians greater choice of treatment options.


Heart rate variability (HRV) analysis has emerged as a simple and non-invasive technique to indirectly evaluate the autonomic nervous system (ANS), and it is considered a sensible and advanced index of health status. Pulsed electromagnetic fields (PEMFs) are widely used in clinical settings for improving the health status of individuals with chronic musculoskeletal pain. The aim of the present single-blind, randomized, placebo-controlled parallel pilot study was to investigate the acute effect of a single session of PEMFs stimulation by a PAP ion magnetic induction (PAPIMI) device on ANS activity, as measured by HRV, in patients with chronic musculoskeletal pain, and compare such effect with that induced by a sham (control) PAPIMI inductor. Thirty-two patients were randomized into two groups: PAPIMI intervention (PAP) (n = 17) and sham PAPIMI intervention (SHAM-PAP) (n = 15). HRV was assessed before and following the interventions. The PAP group showed a significant increase in all values of the time-domain parameters  and the HF component of HRV, suggesting a parasympathetic effect. In contrast, the SHAM-PAP group showed no significant differences in all HRV indices following the intervention. Preliminary findings suggested that PAPIMI inductor could influence ANS activity and provided initial evidence of the potential physiological response induced by the PAPIMI device. The autonomic nervous system (ANS) plays a critical role in the regulation and coordination of the physiological processes in human biological organisms, and individual differences in autonomic balance have long been associated with health and pathological conditions ,2,3.The ANS is assumed to be composed of two major antagonistic subsystems that commonly act in dynamic balance: the sympathetic branch, involved in regulating energy mobilization, and the parasympathetic branch, implicated in vegetative and restorative functions ,5. Both The dynamic balance between distinct components of the ANS can be threatened and altered by metabolic (inner) and environmental  stimuli, which may cause a condition of autonomic imbalance. Specifically, the loss of autonomic balance, in which one branch of the ANS prevails over the other, is characterized by a lack of dynamic adaptability and of the health of the organism. A substantial amount of empirical evidence indicates that a host of pathological conditions and diseases are associated with autonomic dysregulation, in which, typically, the sympathetic system is hyperactive and the parasympathetic system is hypoactive ,7.Among the methods adopted to assess ANS function, heart rate variability (HRV) analysis has emerged as a simple and noninvasive technique to indirectly evaluate the autonomic activity, representing one of the most important quantitative markers of ANS balance/imbalance ,10,11,12As regards the link to pathological conditions, it was reported that ANS imbalance is associated with chronic musculoskeletal pain. This common physiological disfunction is defined as a pain that affects bones, muscles, ligaments, tendons, and even nerves; it comprises a number of different pain syndromes such as chronic neck pain, shoulder pain, low back pain, and also pain associated with osteoarthritis and rheumatoid arthritis ,19. As sDifferent non-pharmacologic approaches are available for relieving the pain associated with musculoskeletal disorders . Among tThe PAP ion magnetic induction (PAPIMI) device is a certified and approved medical instrument that belongs to the large family of PEMFs. This device provides a non-invasive, painless, contact-free ion-induction therapy that was shown to be effective for the treatment of refractory seizures , skin woTherefore, the aim of the present single-blind, randomized, placebo-controlled parallel pilot study was to investigate the acute effect of a single-session treatment of PEMFs stimulation by PAPIMI inductor on ANS balance, as measured by HRV, in patients suffering from chronic musculoskeletal pain, and compare such effect with that induced by a sham (control) PAPIMI inductor. We hypothesized that PAPIMI intervention, as compared to the sham one, could induce a more effective parasympathetic response, which would result in an increased HRV.From a population of 95 patients, 32 subjects (17 men and 15 women) with painful symptoms in the musculoskeletal system, aged between 28 and 68 years old (50.06 ± 10.85), were enrolled in the study. Patients were recruited from April to May 2022 from the physiotherapy center “Centro FisioterapicoApuano” in Lucca  where the study was also conducted.All patients who were considered eligible for the study had chronic musculoskeletal pain (of more than 3 months’ duration)  and had Participants were recruited after being evaluated by a physiotherapist from the center, who confirmed a diagnosis of musculoskeletal pain syndrome and collected participants’ pharmacological information through an in-person interview. Prior to the start of the study, informed consent was read and signed by each patient. The study was approved by the local institutional review committee (Prot. N. 12774E_spe). Each subject was blind to study design, outcome, and group allocation.Patients were randomized into two different groups: PAPIMI intervention (PAP) (n = 17) and sham (control) PAPIMI intervention (SHAM-PAP) (n = 15) . Each paPAP and SHAM-PAP interventions were administered to all patients by a single licensed and registered physiotherapist.TM, Pulse Dynamics, Athens, Greece. Model ASKLIPIOS. Manufacturer characteristics: Input 230 V-50/60 Hz; Power 2500 VA (1.5 KW); Fuse 10 Amp, slow) . In contrast, no significant main effect was found for INTERVENTION  and interaction TIME by INTERVENTION . Post hoc pairwise comparisons showed a significant increase (pre–post interventions) in SDNN scores in PAP group  but not in SHAM-PAP group .For the SDNN index, the results of the mixed ANOVA showed a significant main effect for TIME  was revealed, while no significant main effect for INTERVENTION  and interaction TIME by INTERVENTION  was shown. Post hoc pairwise comparisons revealed a significant increase (pre–post interventions) in RMSSD scores in PAP group  but not in SHAM-PAP group .For the RMSSD index, a significant main effect for TIME , INTERVENTION  and interaction TIME by INTERVENTION  was observed. Post hoc analysis showed a significant increase in NN50 scores following PAP intervention  but not after SHAM-PAP one .For the NN50 index, no significant main effect for TIME  was found, while no significant main effect was reported for INTERVENTION . In addition, no significant interaction TIME by INTERVENTION  was shown. Post hoc analysis showed a significant increase in pNN50 scores following PAP intervention  but not after SHAM-PAP one .For the pNN50 index, a significant main effect for TIME  but no significant main effect for INTERVENTION  and interaction TIME by INTERVENTION . Post hoc analysis showed a significant increase in HF component after PAP intervention  but not after SHAM-PAP one .For the HF band, mixed ANOVA showed a significant main effect of TIME [In the current study, we investigated the influence of a single session of PEMFs stimulation using PAPIMI device on modulating ANS activity in patients with chronic musculoskeletal pain. An HRV analysis was employed in order to detect changes in vagal tone after the intervention.Our results showed that all values of time-domain parameters and HF component of HRV significantly increased following PAP treatment, indicating that PAPIMI device modulated ANS activity by inducing a parasympathetic response. In contrast, no significant differences in all HRV indices were found following the SHAM-PAP intervention.In clinical practice, PEMFs are widely used as a safe and non-pharmacologic intervention for the treatment of musculoskeletal disorders . The benAmong PEMFs, PAPIMI inductor represents a promising ion magnetic field device which has proven to help restore health status in subjects with pathological conditions ,42 charaOur findings shed light on the effectiveness of PAPIMI device in inducing a health status-related parasympathetic response, as indirectly shown by an increased HRV, in patients with chronic musculoskeletal pain. A possible hypothesis that could explain such effect is related to the influence PEMFs have on the membrane potential of body cells ,62,63. IFinally, this is the first study investigating the influence of PAPIMI device on the ANS activity in patients with chronic musculoskeletal pain. Taking into account the low risk of side effects and the high tolerance of PEMFs intervention, findings from our pilot study indicate that PAPIMI inductor could be considered a potentially promising device in clinical practice for the treatment and management of chronic musculoskeletal pain, thus further contributing to improvements in patient health status. To the best of our knowledge, in the literature, only two studies have explored the effects of PAPIMI inductor in human subjects ,42. TheySome limitations concerning the present pilot study should be addressed. First, the number of participants remains relatively small. Second, a comparison with a control group of healthy subjects was not planned for this study. Future non-pilot studies should preferably include a larger patient sample and a group of healthy individuals as well. Third, we did not provide an evaluation of subjects’ feeling of well-being or pain perception that could provide information on the responsiveness of patients to PAPIMI intervention. Nevertheless, it is worth mentioning that the analysis of the cardiovascular autonomic control seems to be more sensitive than a self-reported measure of pain for estimating the effectiveness of a non-pharmacological treatment in patients with musculoskeletal pain . Fourth,Future studies exploring the effect of PAP treatment in subjects with chronic musculoskeletal pain should be carried out with a longer intervention period ,31,32,33In this study we investigated the effect of PAPIMI intervention on ANS activity in patients with chronic musculoskeletal pain. Results showed that PAPIMI inductor, as compared to a sham (control), induced a significant effective parasympathetic response, which resulted in an increased HRV. Since musculoskeletal pain conditions have been associated with a reduced HRV ,24,25,26