Itremains challenging in clinical practice to perform optimal pain management following bariatric surgeries. Acupuncture (AC) is an effective method of postoperative pain management, but its clinical efficacy depends on the rationale used to select AC points.We developed a method to identify individual patterns of pain and a corresponding set of acupoints (corrAC) based on the relative pressure sensitivity of six abdominal visceral pressure points, i.e., the gastrointestinal (GI) checkpoints (G1–G6). Patients with moderate to severe pain were included and received a single AC treatment following surgery. The visual analog scale (VAS) score, pain threshold, and skin temperature were assessed before AC and at 5 min, 1 h, and 24 h following AC. AC was performed with 1-mm-deep permanent needles.p < 0.0001) and a significant increase (37%) in the pain threshold (p < 0.0001). In this group, a significant increase in skin temperature above G1, G3, G4, and G5 was observed. Patients receiving nonAC showed neither significant pain reduction nor significant changes in pain threshold. The skin above G3 and G4 did not reveal temperature changes.From April 2021 to March 2022, 72 patients were included in the analysis. Fifty-nine patients received corrAC, whereas 13 received a noncorresponding AC (nonAC) as an internal control. Patients receiving corrAC showed a significant reduction (74%) in pain at 5 min after treatment (Checkpoint AC may be an effective tool in postoperative pain therapy after bariatric surgery. Vegetative functional involvement might be associated with pain relief.The online version contains supplementary material available at 10.1007/s11695-023-06654-8. Bariatric surgery is a successful method for achieving long-term weight loss among individuals with severe obesity . It is cAcupuncture may be regarded as a reflex therapy, as it involves eliciting vegetative reflexes via acupoints on the skin. These acupoints are located on meridians, which are neurosensory organs involved in homeostatic vegetative regulation of the body. Stimulating acupoints can lead to functional changes in tissues along the meridian, including the skin, underlying muscles and joints, and other tissues, that are essential for the treatment of various conditions, such as wound pain  or posttraumatic pain. Functional modulation also occurs in symptomatic regions of the viscera, such as peristalsis . AcupuncWe developed a novel model to evaluate abdominal dysfunction by comparing pressure sensitivity at defined visceral points: Gastro 1–Gastro 6 (G1–G6). The diagnostic usage of pressure points has a long history in surgery as well as in Chinese medicine. The most well-known point for appendicitis in modern medicine is the McBurney point.We identified six abdominal points located at key regions of control of gastrointestinal peristaltic movement and digestion Fig. . We alsoWe hypothesize that complex dysfunctional vegetative patterns are connected to these points, which we call G1–G6 syndromes, and that these patterns require the use of a matching set of acupoints to personalize AC therapy, i.e., checkpoint acupuncture. To date, this system is routinely used to treat various abdominal conditions, such as irritable bowel disease and food intolerance, based on the assumption that the complaints are predominantly based on dysfunctional vegetative symptoms. Since GI dysfunctions are often associated with disorders of the autonomic nervous system  and painTo verify the applicability of the concept of checkpoint acupuncture in patients after bariatric surgery, we conducted this trial to evaluate its analgesic effect in the postoperative course.This study used a prospective, single-blinded, cohort design to investigate the effects of acupuncture treatment in patients after bariatric surgery. Acupuncture was performed in addition to postoperative standard care, including pain control treatment. Informed consent was obtained prior to enrollment in accordance with a clinical trial protocol approved by the local Ethical Committee. The study was conducted at a university hospital and registered in the German Clinical Trials Register (DRKS00025579).Adult patients who underwent bariatric surgery were screened consecutively. The inclusion criterion was a postoperative pain score of ≥ 3 on a 10-point visual analog scale (VAS). Patients with needle phobia, previous experience with postoperative acupuncture, chronic pain syndrome prior to surgery, polyneuropathy, relevant coagulation disorders, impaired mental state, or poor communication skills were excluded.All patients received a standardized anesthesia with a multimodal analgesia technique. Anesthesia was induced with sufentanil (0.3–0.5 mg/kg), propofol (1.5–2.0 mg/kg), and esketamine (0.5 mg/kg) and maintained with continuous infusion of propofol an esketamine. Patients received metamizole and a prophylactic anti-emetic therapy consisting of dexamethasone 8 mg i.v. and granisetron 1 mg i.v. Supplemental intraoperative analgesia was provided using sufentanil or esketamine at the discretion of the attending anesthetist.All patients underwent surgical site infiltration with 0.25% bupivacaine at the beginning of surgery. A 1-cm skin incision was made 15 cm below the xiphoid paramedian-left. The first 12-mm optical trocar was then inserted through this incision under visual control. The constriction of the pneumoperitoneum was 12 mmHg. Additional 12-mm disposable trocars were inserted in the left upper abdomen at the mammillary line and in the right upper abdomen at the mammillary line. A 5-mm trocar was inserted on the left below the costal arch and anterior axillary line. Using a subxiphoid incision, another 5-mm trocar was set, through which the left liver was lifted ventrally using forceps.According to our internal hospital indication guidelines, RYGB was recommended if gastroesophageal reflux disease (GERD) was diagnosed previously. VSG was recommended particularly to patients with a BMI ≥ 50 kg/m2, or to young female patients who desired to have children in the future.All patients were monitored in the postanesthesia care unit (PACU) and transferred to a surgical ward as soon as their vital signs were stable. On the surgical ward, they received a scheduled baseline analgesic such as acetaminophen  or dipyrone . The first-line rescue analgesic was an opioid such as controlled-release oxycodone with naloxone . The second-line rescue analgesic was immediate-release oxycodone . Antiemetics were administered on demand. After surgery, clear fluids were allowed if patients denied nausea and vomiting. On the following day, patients started with a fluid diet including clear fluids and protein shakes. They were discharged from the hospital on the second day after surgery if they did not show any signs of complications such as bleeding or leakage of the gastrointestinal tract, tolerated the fluid diet (at least 1 L per day), and had well-controlled pain.The intensity of subjective pain—ranging across a continuum from none (0) to an extreme intensity of the pain (10)—was assessed immediately before AC and at 5 min, 1 h, and 24 h after AC.The most sensitive pressure point (ppp) was identified by comparing the sensitivity at all abdominal checkpoints . Some of these points are referred to as trigger points or “alarm points” and are of diagnostic value , 19.However, abdominal checkpoints can also be localized via topologic orientation through acupoints, which are abundantly present on the abdomen Table .The target regions of the visceral G points were first observed by medical doctors in patients with a variety of functional abdominal problems in an outpatient clinic. They observed that the pressure sensitivity of these target regions may be an important clue for the individual discrimination of disease patterns and the individual selection of acupoints . These aA few exploratory pilot studies were performed on the measurable physiologic effects of the G point concept as master’s theses; the results of which were summarized in a published paper . SurgeonUsing an algometry device (PCE-PTR 200 N), the pressure was slowly increased on the ppp until it was perceived as uncomfortable. This pressure was defined as the mechanical pain threshold.  AlgometrContact-free temperature measurement on the abdominal skin was performed  as an indicator of change in microcirculation. The temperature was measured immediately before AC and at 5 min, 1 h, and 24 h after AC.For AC, a commercially available set of permanent needles with an in-built prefabricated needle applicator  was used to ensure consistent insertion pressure, depth, and stimulation intensity. These needles limit the depth of insertion into the skin to 1 mm.Before AC, the pressure sensitivity of G1–G6 was manually compared to determine the ppp. If the most pressure-sensitive point was, e.g., above G1, a G1 syndrome was diagnosed. Based on the diagnosis, a standardized set of acupoints was needled to conduct the corresponding personalized checkpoint acupuncture (corrAC) . The acupoints used within these strategies are also commonly used for abdominal complaints, although they have been used to treat other types of G-syndromes. They may serve as internal controls. Patients received rescue analgesic if their pain persisted after acupuncture therapy.Clear acupuncture rationales were followed, in accordance with the checkpoint concept (G-points) described in previous papers, based on reflections apparent in the Shang Han Lun , a tradiDetails of needling included an identical number and depth of needling with identical needle retention times of 5 min, 1 h, and 24 h. There was no needle stimulation in the verum group and controls. Diameter, length, pressure of insertion, and depth of insertion were unchangeably identical due to the constructive features of Sedatelec permanent needles and their respective applicator. We did not seek subjective needle sensation (de qi) or other individual responses.The treatment regimen was identical in all groups, as there was only one treatment after surgery, with permanent needles remaining over the whole observation period. Oral communication was restricted to a minimum in a stress-avoiding atmosphere.No further interventions of Chinese medicine (CM) were administered, and no further lifestyle advice was given. Patients were uniformly informed 1 day before treatment using a standardized information and explanation sheet. The setting and context of treatment were identical in terms of hospital rooms, time of onset of therapy, nutrition, and fluid intake.All practitioners had performed acupuncture on a daily basis for more than 5 years.Control or comparator interventions. The rationale for the control in the context of the current research question is that the strictest control intervention is to needle a set of acupoints with identical depth, intensity, and number instead of placebo needles or non-acupoints or any other type of sham acupuncture. For this purpose, we used two sets of acupoints that are frequently used for abdominal complaints but empirically when G1 or G6 are the dominant visceral pressure sensitive points within an individual. This strategy was used with the aim of identifying reliable or unreliable sets of control points for further usage based on STRICTA guidelines.All data were collected in accordance with the STRICTA criteria .Clear act test was used, as appropriate. Repeated-measures ANOVA was used to investigate changes over time. Furthermore, a two-way repeated measurements ANOVA was performed to analyze the impact of measurement time and a group factor on a quantitative outcome simultaneously. Furthermore, the Scheffé post hoc test was conducted to perform pairwise comparisons. These analyses were performed with the SAS procedure PROC MIXED with time and group as fixed factors and patients’ ID as a random factor.For statistical analysis, SAS software, release 9.4  was used. Quantitative variables are presented as the mean ± standard deviation; for qualitative factors, absolute and relative frequencies are given. To compare two groups, Fisher’s exact test or a 2-sample p < 0.05 (*).GraphPad Prism was used to create the figures. The result of a statistical test was considered significant when Among the included patients, 53 underwent laparoscopic Roux-en-Y gastric bypass (RYGB) and 19 underwent laparoscopic vertical sleeve gastrectomy (VSG). Men were more likely to undergo VSG than RYGB. The VSG group had a higher weight and BMI than the RYGB group, as shown in Table Between April 2021 and April 2022, 72 patients were included in the study. Sixty patients 83%) were females, and 12 patients (17%) were males. The mean age was 42.6 ± 11.4 years (range: 23–66). % were fep = 0.57). In each group, one postoperative complication was noticed: one patient had metamizole-induced leukopenia of low severity. One patient in the corrAC group showed an anastomotic leaking of the pouch, which was successfully treated with endoluminal vacuum therapy.The average length of stay was comparable in both groups  showed G3 syndrome. In 13 patients (18%), G5 was the predominantly pressure-sensitive point. Five patients (7%) had G2 syndrome, one (1%) had G1 syndrome, and one (1%) had G6 syndrome.p = 0.5162) between the groups before AC. Since the two-way ANOVA including the factors time and group (corrAC vs. nonAC) showed a significant interaction term (p = 0.0008), separate one-way ANOVAs were performed for both groups. For patients who received a G-point-corresponding AC (corrAC), significant changes over time were observed , as well as an increase from 5 min to 1 h (p = 0.0203) followed by a significant reduction from 1 to 24 h (p = 0.0466). For patients with noncorresponding AC, one-way ANOVA showed nonsignificant results  was not significantly different p = 0.516 between Comparing the pain level developments after AC for both the corrAC and nonAC groups, the former group showed significantly lower pain levels, as shown in Fig. p = 0.3345).Before AC, the mean VAS score for all patients was 5.3 ± 1.6 , indicatp < 0.0001) but no difference between the RYGB and VSG (p = 0.5673) and no interaction between treatment and time (p = 0.4657), indicating that changes in VAS scores over time were similar in both treatment groups. The Scheffé test revealed a significant reduction in pain from baseline to 5 min (p < 0.0001), followed by a significant increase from 5 min to 1 h (p = 0.0019) and then a significant reduction again from 1 to 24 h (p = 0.0111).CorrAC led to a significant pain reduction for RYGBs and sleeve gastrectomies Table . Two-wayp = 0.9694; see Table p = 0.0324, supplementary materials Fig. p < 0.0001, supplementary materials Fig. p = 0.1138, supplementary materials Fig. This subjective pain was objectified by evaluation of the pain threshold using algometry. The initial average pain threshold was reached at 15.7 ± 7.0 N. The initial average pain threshold was 15.7 ± 7.0 N. Before intervention, no difference in the pain threshold was observed between the groups receiving either corresponding or noncorresponding treatment  on the skin , 25, 26,Our data were acquired by rigorous application of the STRICTA criteria  for repoFurthermore, this finding can be explained by the skin temperature changes. Skin temperature above G3 and G4 was slightly elevated only at the G point corresponding to AC of G3 syndrome, whereas treatment by other strategies would not elevate this skin temperature above these points and had no significant pain-relieving effect. We hypothesize that this increase in microcirculation after AC may support the theory that this is part of the vegetative reflex mechanisms underlying the pain-reducing effect. Further studies are needed to investigate this phenomenon.Considering that pain management, especially within 24 h after bariatric surgery, remains a major challenge , AC mighTo the best of our knowledge, our data represent the first usable and feasible strategy of somatic acupuncture in postoperative pain of bariatric patients .Our data show that abdominal checkpoint acupuncture may present an effective complementary tool for postoperative pain management even within enhanced recovery pathways. Using the abdominal pressure points (G1-G6), postoperative pain can be systematically personalized and addressed after surgery. Breaking down the complexity of the functional traditional diagnosis used for acupuncture to a few abdominal pressure points may lead to rational access to effective acupuncture strategies.Based on our results, we developed a triple-blinded RCT to evaluate the effectiveness of acupuncture after abdominal surgeries.Supplementary file1 (DOCX 4280 KB)Below is the link to the electronic supplementary material.


Thirty-eight patients (82.6%) had a satisfactory response and good global perceived effect (GPE) after twelve months. No significant complications were observed during the 12-month follow-up. The ultrasound-guided radiofrequency device designed as a safe, easily applied and encouraging method could avoid revision surgery. It is a promising technique and has shown good results in providing intermediate pain relief. In addition to the limited series reported in the literature, future studies will add meaning to this topic by including it in routine practice.Our study evaluated the clinical feasibility of ultrasound-guided lateral branch radiofrequency neurotomy for sacroiliac joint (SIJ) pain after lumbosacral spinal fusion surgery (LSFS). This prospective study included a total of 46 patients who were diagnosed with SIJ pain after LSFS, did not respond to conservative treatment and therefore underwent ultrasound-guided SIJ radiofrequency neurotomy (RFN) from January 2019 to January 2022. These patients were followed up for twelve months after the procedure. Patients were assessed with the Numeric Rating Scale (NRS) and the Oswestry Disability Index (ODI) preprocedural and postprocedural for 1 month, 6 months and 12 months follow-ups. There was a significant improvement in postprocedural NRS and ODI scores ( Instead of categorically labeling this group of patients with “failed back surgery syndrome—FBSS”, it is essential to identify possible causes for their ongoing or new onset symptoms. A potential reason might be pain originating from the SIJ. The prevalence of SIJ pain due to FBSS is estimated to be 29%2. SIJ is the most likely source of low back pain, particularly in patients undergoing lumbar and sacral fusion surgery.Spinal fusion surgery performed in carefully selected patients with an adult spinal deformity has improved clinical outcomes when attention is given to restoring spinopelvic sagittal alignment parameters. Despite this, the frequency with which surgery had failed to relieve symptoms remains as high as 20–40%3. Lumbosarcral spinal fusion surgery (LSFS) results in increased stress on the SIJ. The mechanical response seen in SIJ after spinal fusion is similar to that occurring in the mobile segments adjacent to the fused spine, with increased mobility and an increase in surface stress, and articular surfaces were confirmed by a biomechanical study. The frequency with which SIJ pain contributes to persistent low back pain after LSFS has been reported to range from 32 to 42%5. There has been an increase in the number of lumbar and sacral fusion surgeries over the past 10 years6. In a multicenter study, it was reported that such surgical procedures yielded better improvement than conservative treatment. Following fusion surgery, some patients may have recurrent and new low back pain that is different from that seen before surgery. Almost all prior injection techniques under sonography required firm solutions by fluoroscopy or computer tomography (CT) images, and our study used ultrasound guidance to perform RFN for SIJ pain after LSFS. Ultrasound guidance is increasingly being explored for a variety of interventional spine procedures. Ultrasound (US) imaging has significant advantages, as it is easily accessible and does not use ionizing radiation, portability, accessible to US equipment, and the reduced cost of US equipment. This study aimed to evaluate the preliminary clinical results of our proposed US-guided SIJ RFN technique. The outcome of this study was the changes in pain intensity and function according to the US-guided SIJ RFN. We hypothesized that the US-guided SIJ RFN would significantly reduce SIJ pain after lumbar fusion and improve function and quality of life.The SIJ creates the lowest segment of the spinal axis and is the largest axial joint in the bodyThere were forty-six eligible patients. The mean age was 51.7 ± 15.3 years old, and the majority were male patients . Before the procedure, pain was assessed by NRS and ODI (30.4% of patients with cripples). The characteristics of the patients are presented in Table p < 0.001). The NRS at the one-month, six-month and twelve-month reexaminations showed a reduction versus the pre intervention NRS . The outcome measured by ODI is presented in Table The terms of the Oswestry Disability Index, the ODI before RFN was 59.1 ± 13.6 . A significant difference in ODI was detected after RFN. The ODI mean (± SD) at 1, 6, and 12 months after the procedure was 23.9 ± 7.6, 24.8 ± 8.5, and 30.0 ± 12.0, respectively. The suffered cripple patients (30.8%) improved function early in the first month of post-procedural, there was no patient have cripple ODI after 12 months of treatment (0%). Patients who received radiofrequency treatment reported significantly lower ODI scores at 1, 6, and 12 months compared to their baseline scores. The change in ODI before and after the intervention at 1, 6, and 12 months is statistically significant  had unilateral and 28 (60.8%) had bilateral SIJ-originated pain. The use of multiple maneuvers for provoking SIJ pain is a reliable test for the presence of SIJ pain. Thus, three positive SIJ provocation tests are important in terms of diagnostic. However, we found no studies that exclusively evaluated stimulation tests in patients with SIJ pain after sacral surgery10.The most common painful sites for SIJ pain are the hips (94%), followed by the lower lumbar region (72%), lower extremities (50%), groin area (14%), upper lumbar region (6%) and abdomen (2%). Maigne and Planchon have suggested that the only criteria characterizing SIJ pain following lumbar fusion are a distribution pattern of pain different from that present before surgery. Almost all of the patients had pain distributed to the hips, back and side of the thighs6. One of the three possible causes of SIJ pain is increased mechanical load transfer onto the SIJ after lumbar or lumbosacral fusion. Ha et al. found a higher incidence of SIJ degeneration in patients with fusion to S1 than in those with fusion to L511. All the above mentioned studies have reported similar results to the results of our research.The most commonly reported pain in adults is low back pain. In addition to being an economic burden for society, a growing and expanding series of patients with low back pain have been observed. There has been an increase in lumbar lumbosacral fusion surgery in the last 10 years. Some authors have suggested that the SIJ plays a role in postoperative pain experienced by patients undergoing lumbar fusion surgeryp = 0.145)11.The results of this study are a group of patients with fusion ending at S1 had more severe pain than the L5 group of patients. The mean NRS score was 7.85 in the S1 group and 6.65 in the L5 group in our study. The S1 group of patients had more severe pain than the L5 group. Our study indicated that the mean NRS score significantly improved in the L5 fusion group from 6.65 at the time of onset to 3.30 at the time of final follow-up; however, in the S1 fusion group, it improved from 7.85 at the time of onset to 3.60 at the time of final follow-up. In this study, patients who received an S1 sacral fusion had a lower response than the L5 and above vertebrae stiffening group, but this difference was not statistically significant. Ha et al. also found no significant difference in the decrease after the procedure in VAS scores between the 2 groups' fusion to L5 and S1  lateral crest RFN technique may reduce pain intensity, improve function and improve quality of life for several months post-RFN in those with SIJ pain. Our findings showed a reduction in NRS from 7.33 before the procedure to 3.00 after one month and to 3.46 after a twelve-month follow-up. This study found a significant decrease in SI joint-related pain after radiofrequency neurotomy under ultrasound into the SI joint in patients who still had pain after lumbosacral fusion. This diagnostic strategy confirmed the clinical diagnosis of SIJ syndrome after lumbosacral fusion in 88.5% (54/61) of patients. Our results in 46 patients demonstrated the short-term radiofrequency denervation efficacy of SIJ pain management. No serious complications or side effects were observed in our patients. Almost all of the patients showed a clinically relevant degree of pain relief, with at least a three-point reduction in NRS for pain, representing a statistically significant reduction in mean pain intensity scores.We also noted a trend toward better outcomes based on ODI. In terms of ODI, which indicated the level of disability, there were no cripple patients post-procedural after the one-month and twelve-month follow-ups. Most patients had a better quality of life and even returned to work. The reduction of post-procedural analgesic consumption and ODI were reported in Omar’s research, which studied the effect on 32 patients with radicular pain. ODI decreased significantly after intervention up to 12 months compared to the post-procedural value. GPE for patient satisfaction was positive in 82.6% of patients. Evaluation of GPE 12 months after the procedure was considered a positive response if the patient reported a decrease in pain and an improved ability to perform daily activities and if the patient introduced this treatment to other patients.13. In 2001, Ferrante et al. reported the first bipolar RF technique employed in treating SI joint disorder by creating a strip lesion of the posterior SI joint with RF needles inserted at < 1 cm intervals. As a result, 36% of the patients experienced 50% pain relief for 6 months14. Afterward, conventional unipolar (or monopolar) RF targeting the lateral branches of the primary dorsal rami was adopted in several studies, which resulted in sustained relief for 6 months in over 60% of subjects16. This study utilized a lateral branch block technique similar to the US technique evaluated by Finlayson et al. This technique involved the infusion of local anesthetic at TST1, TST2 and TST3, while the block technique in this study utilized sequential infusion of local anesthetic along the lateral crest from TST1 to TST3 at 1 cm intervals17. The proportion of patients achieving at least a 50% reduction in pain intensity 1–12 months post-RFN was high. In addition, although care was taken by the interventionalists to ensure that the RFN cannulas were placed parallel to each other, parallel placement was challenging to achieve at TST1. The prominence of the PSIS made a purely sagittal, out-of-plane approach to TST1 difficult; therefore, an approach that was between an out-of-plane and in-plane approach was necessary to reach TST1. If the distance between electrodes at the periosteal level was too far apart, an adequate lesion may not have been generated.In recent years, the denervation of sacral lateral branches innervating the SIJ via RF energy has drawn great attention. RF applications for the treatment of chronic pain originating from the SIJ are relatively newer than those used for facet joint syndrome, and there are no large case series in the literature. The mechanism by which RF denervation alleviates pain sensation consists of applying an electrical current generated by radio waves to heat nerve fibers and thus reduce pain signalsIn the future, a randomized trial comparing active and placebo US-guided SIJ RFN techniques would confirm the preliminary findings of this study. The use of a standardized dual US-guided block protocol within the randomized trial would be necessary to minimize false positive diagnostic blocks. To improve clinical outcomes, future studies should also evaluate the characteristics of patients who have a high likelihood of achieving significant pain relief. The factors that can optimize lesion generation for SIJ RFN, such as tip spacing, lesion duration and cannula type, should also be evaluated. In conclusion, clinical outcomes following US-guided SIJ RFN are promising. These findings suggest that US could be used to guide SIJ RFN. Further randomized controlled studies are necessary to establish the effectiveness of this technique.The high success rate in our patient series may be associated with the fact that lumbosacral fusion surgery was included in the present study. We believe that percutaneous interventional RF applications should be used in neurosurgical operations for the diagnosis/treatment of low back pain following fusion surgery. SIJ pain should be considered, particularly in patients with pain radiating to the hips and back of the thigh following fusion surgery with fusion ending at the level of S1 and L5. The ultrasound-guided RF device designed as a safe, easily applied and encouraging method will eliminate unnecessary and accurate surgical interventions and revision surgeries.There are some limitations in this study. First, there was no definitive control group; neither the patients nor the doctor was blinded. Second, this was not a double-blind, placebo-controlled trial. This design was not chosen because the patient was in severe pain and it was considered unethical to use a placebo. Third, data were affected by lost-contact patients during follow-up. The long-term effects of this procedure, the effectiveness of SIG tests, and the safety of the used RFN require a more significant number of studies in the future. In addition to the limited series reported in the literature, future studies will add meaning to this topic by including it in routine practice.This prospective study was carried out on 46 patients who previously underwent lumbar or lumbosacral fusion surgery and were admitted to our outpatient clinic between January 2019 and January 2022 with postoperative persistent chronic pain (more than 6 months), which is different from preoperative pain.Lumbar fusion that involved L5 or S1Pain consistent with SIJ origin graded on NRS ≥ 5, unilateral or bilateral pain.50% pain relief after sacral lateral branch block.Positive Fortin sign .No satisfactory improvement of symptoms with conservative treatment: non-steroidal anti-inflammatory drugs, tramadol, gabapentinoids  and physical therapy.Patients were included if they met the following criteria:Symptomatic lumbar pathology.Inflammatory, tumoural, traumatic or infectious disease of the SIJ.Hip osteoarthritis or history of hip arthroplasty.No disc herniation, instability or pseudoarthrosis.Symptoms of severe nerve damage including motor paralysis, muscle atrophy, peripheral neuropathy, arterial disease, malignancy and cauda equina syndrome.Allergy to the drugs used in this study.Prior epidural injection in the past 3 months: nerve root injection and caudal injection.Coagulation disorder.Pregnancy.The following exclusion criteria were used:At least 3 positive physical examination maneuvers: Faber , POSH (posterior shear), REAB (resisted abduction), Gaenslen's test and distraction test.Pain at the trochanteric insertion of the gluteus medius.Maximum pain in a seated position.In addition to the Fortin test, the following clinical signs were met in our population:Radiographs and MRI of the lumbar spine and hips.Radiographs centered over the SI joints.MRI to look for degenerative or inflammatory changes in the joint.The sacroiliac imaging work-up consisted of the following:17 A long-acting local anesthetic  without vasoconstrictors was injected at each needle placement. After the procedure, NRS levels were assessed, and physical and neurological examinations were repeated.A diagnostic test was performed for patients with LBP after lumbosarcral spinal fusion surgery was resistant to medical treatment and met the criteria through clinical and imaging examination. A standardized US-guided lumbar approach was utilized for pararadicular spinal injections by LOGIQ P5 . A 2–5 MHz convex probe and a prone position were required. Initially, the sacrum was defined in a sagittal US image in the midline plane starting from the spinous processes to the caudal patient's body Fig. . LateralThere were 54 patients in whom SIJ pain was confirmed by SIJ blockage, a conservative treatment method, and the electrode conventional radiofrequency denervation method was applied. In those patients with a positive response, defined as temporary pain relief  measured by NRS, the surgeon began conducting the RFN procedure similar to the SIJ block with the radiofrequency electrode  was placed TST from S1 to S3 under ultrasound. The position of the needle tip was examined by using the Stimulation Program of the Radiofrequency generator machine . Sensory stimulation was performed at 50 Hz, and the patient was asked to notify the operator in case of tingling, electric shock-like sensation, or tingling. For each grade, paresthesia was achieved ≤ 0.5 V. Then, a motor stimulus was applied at ≤ 2 Hz through the paresthesia points and ensured no muscle contraction in the lower extremities. Afterward, RFN was applied at 80° for 3 min.Vital signs were checked during the procedure. Neurological check-ups of the lower limb included motor examination in form tone, muscle strength, reflexes and sensory examination. Patients were evaluated 2 h after the procedure and discharged with advice to avoid too much bending, lifting heavy weights or walking distances and asked to reexamine at 1 week, 1 month, 6 months and 12 months. The NRS and Oswestry Disability Index (ODI) were recorded at all times. During the period of recruitment (from Jan 2019 to Jan 2022), there were 54 eligible patients. Due to the COVID-19 pandemic and serious effects on Vietnam beginning in May 2021, posterior procedure assessment had to be stopped because of isolation, and 8 patients were lost to follow-up. Therefore, only 46 patients were followed up in our 12-month study, as shown in the flow chart in Fig. A physician unaware of the patient's team assignment obtained all outcome data during scheduled follow-up visits. Between the procedure and the initial follow-up, contact between the patient and the investigator should not be allowed except in an emergency.3 and GPE  by Dutta18. The outcome parameter was assessed after one month, 6 months and 12 months using NRS and ODI and after 12 months using GPE.The patients’ characteristics were sex, age and baseline data upon admission. The data were collected, including the NRS and Oswestry Disability Index (ODI) used by CohenMy pain has improved/worsened/stayed the same since my last visit.The treatment I received improved/did not improve my ability to perform daily activities.I am satisfied/not satisfied with the treatment I received and would recommend it to others.A 2-point or ≥ 50% reduction on the NRS was deemed to represent clinically meaningful improvements in pain intensity. The Oswestry Disability Index (ODI) calculated 10 items, including pain, individual function and personal comprehensive function. The minimum score for each item is 0 (good state), whereas the highest score is 5 (poor state). The ODI referred to the percentage of the sum of scores from all 10 items out of 50. A positive GPE was defined as an affirmative response to the following three questions:The study was approved by the Institutional Review Board of the University of Medicine and Pharmacy at Ho Chi Minh City and designated 115/ĐHYD-HĐĐĐ. The study was prepared on the ethical principles of the Declaration of Helsinki. The informed consent form will contain extensive information about this trial, including the purpose of the trial, the study design, potential risks and benefits associated with the trial and the participant’s rights and responsibilities.Mean, standard deviation, median, interquartile, frequency and percentage were used to describe the data. Chi-squared tests, Fisher’s exact tests and Paired-Sample T-tests were used to evaluate the association between patient characteristics and pain degree. All statistical tests were two-sided with a significance level of 0.05. Continuous data before operation with non-normal distribution were analyzed using the Mann–Whitney U-test, Wilcoxon Signed Rank test. Data were analyzed using the SPSS 25.0  software.Supplementary Information.


Over two thirds of individuals with low back pain (LBP) may experience recurrent or persistent symptoms in the long term. Yet, current data do not allow to predict who will develop chronic low back pain and who will recover from an acute episode. Elevated serum levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) have been associated with poor recovery and persistent pain following an acute episode of LBP. Inflammatory cytokines may also mediate mechanisms involved in nociplastic pain, and thus, have significant implications in chronic primary low back pain (CPLBP).This study aimed to investigate the potential of urinary TNF-α levels for predicting outcomes and characterizing clinical features of CPLBP patients. Twenty-four patients with CPLBP and 24 sex- and age-matched asymptomatic controls were recruited. Urinary TNF-α concentrations were measured at baseline and after 4 weeks, during which CPLBP patients underwent spinal manipulative therapy (SMT).Concentrations of TNF-α were found to be elevated in baseline urine samples of CPLBP patients compared to asymptomatic controls. Moreover, these values differed among patients depending on their pain trajectory. Patients with persistent pain showed higher levels of TNF-α, when compared to those with episodic CPLBP. Furthermore, baseline TNF-α concentrations and their changes after 4 weeks predicted alterations in pain intensity and disability following SMT in patients with CPLBP.These findings warrant further research on the potential use of urinary TNF-α concentrations as a prognostic biomarker for CPLBP. A large proportion of the general population will be afflicted with low back pain (LBP) at some point in their lifetime , particuAiming to identify those who recover from an acute episode of LBP and those who do not, efforts have been directed toward investigating the patients’ trajectories . Most paSeveral potential inflammatory biomarkers have been identified in the context of LBP . Of thesin vitro production of TNF-α in whole blood cultures of patients with CPLBP was significantly reduced after a period of spinal manipulative therapy (SMT)  . These fpy (SMT) , suggestTherefore, the aim of this study was to assess the predictive value of urinary concentrations of TNF-α for outcomes and clinical characteristics in patients with CPLBP. First, we aimed to confirm that baseline urinary concentrations of TNF-α were elevated in patients with CPLBP compared with age-sex matched pain-free controls. Secondly, we compared changes in urinary concentrations of TNF-α over 4 weeks, during which patients received standardized SMT and controls received no intervention. We hypothesized that TNF-α concentrations would decrease in patients with CPLBP, approaching values observed in controls. Thirdly, we examined the predictive value of urinary TNF-α concentrations for clinical characteristics and outcomes in patents with CPLBP that received SMT. We hypothesized that urinary TNF-α concentrations may be used as a biomarker to discriminate patients with CPLBP according to their pain trajectory and to predict clinical recovery.This was a prospective case-control study with longitudinal follow-up, assessing the predictive value of urinary TNF-α concentrations for baseline characteristics and clinical evolution of CPLBP patients undergoing chiropractic instrument-assisted SMT. The study protocol was approved by the Madrid College of Chiropractic Research subcommittee  and the Fundación Jiménez Díaz Hospital Clinical Research Ethics Committee . The study was conducted between January 2018 and December 2022 at the Madrid College of Chiropractic Outpatient Clinic. All experimental procedures conformed to the standards set by the latest revision of the Declaration of Helsinki.Patients were recruited from the population visiting the outpatient clinic for an initial consultation with a chief complaint of CPLBP. Patients seeking care for symptoms of LBP were screened for inclusion and exclusion criteria by performing a complete case history and physical examination, following routine protocols from the outpatient clinic. The inclusion criteria were: being between 18 and 80 years of age and presenting a chief complaint of persistent or recurrent pain ≥3 months, in any anatomical location included between the lower margin of the 12th rib to the lower gluteal folds, with or without referring to the lower limbs . The excA cohort of pain-free controls matched by sex and age to the patient cohort was enrolled to serve as a reference for the levels in inflammatory cytokines that were collected and assessed from the patient cohort. Individuals eligible for the pain-free cohort were to meet the following criteria: aged between 18 and 80 years old, without acute or chronic pain symptoms or diagnoses, and without a current or prior diagnosis of any systemic, inflammatory, neurological, or psychiatric conditions. Pain-free individuals accepting to participate read and signed an informed consent form before urine sample collection. Informed consent was also obtained from all subjects for publication of identifying information/images in an online open-access publication.d = 0.6, an alpha of 0.05 and a statistical power of 0.8 for a mixed model assessing both within- and between-subject interactions. The required sample size was of 24 participants per group [G*Power version 3.1.9.6 . This instrument is a hand-held device  or on the day after being recruited (controls). All participants were instructed to store their urine samples in the refrigerator (∼ 4°C) immediately after collection and until visiting the clinic. Once urine samples were collected, they were immediately aliquoted and stored in a container at −20°C. The procedure was identical for the follow-up sample, which was collected 4 weeks after the baseline sample collection. For patients, this corresponded to the day after the eighth and final SMT session. All participants were requested to refrain from taking any anti-inflammatory medication within 24 h of the dates when both samples were collected.Urinary TNF-α concentrations were measured in duplicate by using specific commercial sandwich enzyme-linked immunosorbent assay (ELISA) following manufacturer’s recommendations  . UrinaryClinical variables describing comorbidities, CPLBP duration and trajectories were collected in the initial clinical interview. The presence of comorbidities included chronic non-painful conditions and pain affecting other body sites. Duration since the onset of the first episode was recorded in years. CPLBP trajectories were classified as either “ongoing,” “fluctuating,” or “episodic” (independent of severity), according to suggested criteria . EpisodiTo examine changes in pain intensity, patients reported their current pain intensity in a NRS ranging from 0 to 10, anchored by two verbal descriptors. The anchor 0 indicated “no pain,” while 10 indicated “worst pain imaginable.” Functional impairment caused by CPLBP was measured by means of the Oswestry LBP Disability Index (ODI) questionnaire, a scale that is widely used in LBP research . Its valp-value threshold of 0.05 was considered statistically significant for all analyses. Values presented in the results section represent mean ± standard deviation. TNF-α data were not normally distributed, therefore, to test a priori hypotheses, baseline urinary TNF-α concentrations were compared between both groups by means of a Welch’s t-test due to heteroscedasticity and non-normal distribution. Further, changes in TNF-α before and after the 4 weeks were analyzed using a linear mixed model  were conducted using these categorical variables as grouping variables. Significant ANOVA effects were decomposed using Dwass-Steel-Critchlow-Fligner pairwise comparisons. In addition, Spearman rank correlation coefficients were calculated to examine the associations between baseline values of TNF-α, the number of years with CPLBP, pain intensity and disability. To explore the predictive value of urinary TNF-α, baseline, follow-up, and percent-changes in TNF-α values were assessed as predictors in simple regression models with follow-up and percent change values in pain intensity and disability as dependent outcomes, for which estimates were obtained using 5000 bootstrap replications.A supplementary exploratory analysis was conducted to identify associations with SM dosage and target site. Spearman correlations were assessed between changes and follow-up values of TNF-α, and the total number of SM applied to low back segments , to the lumbopelvic area and to the whole body.For the thirty-nine patients that were screened for eligibility, twenty-four met the selection criteria and were included in the study. Eighteen patients were women and six were men, with a mean age of 53.9 ± 10 years, and a mean of 11.5 ± 8.3 years with CPLBP . The fifp = 0.002, d = 0.99). Follow-up values were 0.4 ± 1.2 pg/mg for the CPLBP group and 0.3 ± 1.6 pg/mg for the control group. The estimated difference between group means over time was of −3.25 pg/mg , which was statistically significant  were taking non-steroidal anti-inflammatory drugs, this variable was introduced as a categorical covariate in the mixed model to examine the potential confound. The results remained unchanged (interaction: p = 0.003).The mean baseline urinary concentration of TNF-α corrected for urine volume was 3.7 ± 4.6 pg/mg in the patient group and 0.3 ± 1.4 pg/mg in the control group see . The meap < 0.001, d = 2.2 . Baseline values were then calculated separately for patients with ongoing , fluctuating  and episodic  CPLBP. Pairwise comparisons revealed that ongoing pain trajectory levels were significantly different from episodic (p = 0.03), but not fluctuating (p = 0.1). TNF-α levels did not significantly differ between fluctuating and episodic CPLBP (p = 0.12). Moreover, baseline TNF-α did not differ by sex . Fourteen patients presented comorbid conditions with CPLBP (see n = 3), neck pain (n = 3), depression (n = 2), full spine pain (n = 2), headaches (n = 2), type II diabetes (n = 1), anxiety (n = 1), carpal tunnel syndrome (n = 1) and plantar fasciitis (n = 1). There were no differences in TNF-α levels based on the presence of comorbidities .Analyses were conducted to examine differences in TNF-α values at baseline according to sex, pain trajectory, and the presence of comorbidities in the patients with CPLBP. Baseline concentrations of TNF-α were significantly different between subgroups of patients with different pain trajectories  association between the number of years with CPLBP and baseline TNF-α , however, baseline TNF-α only marginally predicted percent changes in pain intensity . Follow-up pain intensity ratings were not predicted by baseline urinary TNF-α . Percent changes in disability could not be predicted by baseline TNF-α , but follow-up values in disability could . The latter model was significant as well , 38.1% of the variance in follow-up ODI scores were explained by baseline TNF-α.Simple regression analyses revealed that baseline TNF-α values explained 20.7% of the variance in changes in pain intensity . Both models were also significant: F = 41.1, p < 0.001 for pain intensity and F = 11.0, p = 0.003 for disability. However, changes in TNF-α did not predict follow-up values in pain intensity  nor disability .Regression analyses with the percent change in TNF-α as a predictor showed that 65% and 33% of the variance in pain intensity and disability percent changes, respectively, could be explained by fluctuations in TNF-α . See Associations between follow-up values and percent changes in TNF-α with the number of SM received were examined with exploratory purposes. However, no strong or significant associations were detected, with the exception of a marginal association between the total number of lumbopelvic manipulations and changes in TNF-α  using visual pain trajectories may not be as reliable as indicated by previous data . In futuUrine samples were collected during different seasons for the CPLBP (January to April) and control (September to January) groups. Seasonal variations of serum TNF-α were reported in conditions with seasonal variability, though not for healthy individuals. The highest TNF-α values were observed during summer-fall, and the lowest from January to spring . This paThis exploratory study presents evidence suggesting that urinary levels of TNF-α may serve as a potential biomarker for patients with CPLBP. Specifically, urinary TNF-α levels discriminated patients with CPLBP from pain-free controls in our sample. These results warrant further study to assess urinary TNF-α levels among patients with different pain trajectories. In addition, our findings indicated that baseline values and fluctuations in TNF-α could predict pain intensity and disability outcomes. Consequently, urinary TNF-α levels may potentially reflect the involvement of inflammatory mechanisms in CPLBP evolution, although this remains to be examined. Further research, preferably in the form of a randomized controlled trial, is needed to better ascertain the utility of this potential biomarker for CPLBP.The raw data supporting the conclusions of this article will be made available upon reasonable request, without undue reservation.The studies involving human participants were reviewed and approved by the Madrid College of Chiropractic Research subcommittee  and the Fundación Jiménez Díaz Hospital Clinical Research Ethics Committee . The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.CG-M: conceptualization, methodology, investigation, formal analysis, and writing—original draft preparation. MP-T and AM: investigation, formal analysis, and manuscript revision. FC-B: investigation, resources, and manuscript revision. MP: supervision, funding acquisition, and writing–review and editing. AO-D: conceptualization, methodology, funding acquisition, supervision, writing–review and editing, and approval of final version. All authors contributed to the article and approved the submitted version.


The pathogenesis of chronic chest pain after cardiac surgery has not been determinate. If left untreated, postoperative sternal pain reduces the quality of life and patient satisfaction with cardiac surgery. The purpose of the study was to examine the effect of chest inflammation on postoperative pain, risk factors for chronic pain after cardiac surgery and to explore how chest reconstruction was associated with the intensity of pain.The authors performed a study of acute and chronic thoracic pain after cardiac surgery in patients with and without sternal infection and compared different techniques for chest reconstruction. 42 high-risk patients for the development of mediastinitis were included. Patients with mediastinitis received chest reconstruction (group 1). Their demographics and risk factors were matched with no-infection patients with chest reconstruction (group 2) and subjects who underwent conventional sternal closure (group 3). Chronic pain was assessed by the numeric rating scale after surgery.The assessment of the incidence and intensity of chest pain at 3 months post-surgery demonstrated that 14 out of 42 patients across all groups still experienced chronic pain. Specifically, in group 1 with sternal infection five patients had mild pain, while one patient experienced mild pain in group 2, and eight patients in group 3. Also, follow-up results indicated that the highest pain score was in group 3. While baseline levels of cytokines were increased among patients with sternal infection, at discharge only the level of interleukin 6 remained high compared to no infection groups. Compared to conventional closure, after chest reconstruction, we found better healing scores at 3-month follow-up and a higher percentage of patients with the complete sternal union.Overall, 14 out of 42 patients have chronic pain after cardiac surgery. The intensity of the pain in mediastinitis patients significantly decreased at 3 months follow-up after chest reconstruction. Thus, post-surgery mediastinitis is not a determining factor for development the chronic chest pain. There is no correlation between cytokines levels and pain score except interleukin 6 which remains elevated for a long time after treatment. Correlation between sternal healing score and chronic chest pain was demonstrated. CTP hasAnother important current problem associated with thoracic pain after surgery is a new persistent opioid use. Unfortunately, patients undergoing open thoracic/cardiac surgery had the highest rate of prolonged opioid use compared with other surgical cohorts . Others To the best of our knowledge, detailed pain assessment in acute chest inflammation and the healing process of deep sternal infection was not reported before. Deep sternal wound infection with mediastinitis is one of the most devastating complications after cardiac surgery . MediastThe primary aim of the study was to examine the risk factors for chronic thoracic pain after cardiac surgery in patients with deep sternal infection and to assess the link between inflammatory biomarkers, and chest pain. A secondary aim was to validate if the newly suggested chest reconstruction technique can improve sternal healing and reduce post-cardiac surgery pain.2.2.1.In this study, we included 42 patients who were at an increased risk of developing deep sternal infection (mediastinitis) after undergoing cardiac surgical procedures. Of these patients, 14 developed deep sternal infection , as defined by the acceptable criteria described below in the Results section Patients were followed up clinically and the pain was assessed both during their hospital stay and in the outpatient follow-up setting. The patient's screening consisted of a physical examination including an assessment of wound healing, CT imaging, a personal interview about pain level, and molecular analysis of cytokines proinflammatory factors and C-reactive protein (CRP). All patients received a similar anesthesia protocol that is routinely used in our department.The postoperative analgesia regimen included HYDROmorphone (DILAUDID) injection of 0.5 mg intravenous and an Oxycodone (Roxicodone) tablet of 5–10 mg. Acetaminophen (paracetamol) and acetaminophen–codeine tablets (500 mg acetaminophen–30 mg codeine) were used as adjunctive analgesics. Some patients received non-steroidal anti-inflammatory drugs (NSAD). However, many doctors avoid prescriptions for NSAD because of concerns about bleeding and renal dysfunction.2.2.The Institutional Review Board at the Atrium Health Sanger Heart and Vascular Institute and Wake Forest Medical School approved and reviewed the study. All patients were informed and gave written consent. The current study is case-control. Group 1 and 3 were retrospective studies because we collected the information about patient's past. In group 2 patients are followed over time and data about them is collected as their characteristics in prospective manner.2.2.1.The groups matching was based on the number of patients, the technique of chest closure after surgery, demographic characteristics, and comorbidities such as diabetes, hypertension, chronic obstructive pulmonary disease (COPD), and choice of cardiac procedure such as coronary artery bypass surgery (CABG), valvular or aortic procedure.2.3.Demographics and clinical characteristics were collected from the hospital's electronic health record. All patients participated in individual interviews with clinicians focused on pain intensity and pain management. Patient interviews were scheduled on day one, the day of discharge, one month, and three months after surgery.2.4.Diagnosis of deep sternal infection was based on the following findings: wound tenderness, purulent drainage, cellulitis, fever with or without leukocytosis, and sternal instability. All patients with deep sternal wound infections were classified according to the accepted criteria  includin2.5.Surgical details of chest wall reconstruction have been previously described . BrieflyIn cases of deep sternal wound infection (DSWI) accompanied by sternal fragmentation and osteomyelitis, we sometimes opt for sternectomy and closure of soft tissues using various flaps. Alternatively, in select cases of DSWI with fragmentation, we perform minimal sternal debridement. If the tissue appears healthy, we proceed with longitudinal rigid fixation. Following multiple washouts, wound vac therapy, and attainment of negative cultures, we proceed with definitive closure. Our approach has demonstrated favorable long-term outcomes in carefully selected patients. Although not routine, considering PET scans in specific cases may be worth considering. One notable advantage of our technique is the expedited re-entry process. Our plates are securely affixed along the lateral edge of the sternum, approximating the sternal halves using regular cerclage wires. This configuration protects the sternum from wire-induced damage. In the event of re-entry, the wires can be readily cut, simplifying the procedure. Another advantage is that the plates remain in place during re-entry, allowing for closure using new wires .2.6.Possible pre- and intraoperative risk factors were analyzed as independent predictors of CTP. These factors included insulin-dependent diabetes mellitus, obesity based on body mass index, chronic obstructive pulmonary disease (COPD), previous sternotomy, arterial hypertension, peripheral vascular disease, renal failure, recent myocardial infarction up to 1 month before the surgery, unstable angina, and immunosuppressed state. Intra- and postoperative risk factors included duration of the surgery, cardiopulmonary bypass, use of internal mammary arteries, and length of intensive care unit (ICU) stay.2.7.The pain was assessed with a numeric rating scale (NRS) at rest, and on movement using an 11-point scale with 0 labeled as “no pain” and 10 as “worst pain imaginable”. The pain was classified as mild with a score of 1–3, moderate with scores of 4–6, and severe with scores of 7–10. After the operation, the actual pain levels were assessed at four time points. All patients were instructed to use the pain-scoring tool correctly and the physician-investigator carefully checks to differentiate chronic chest pain after surgery from angina or another cardiac pain. The pain was relieved by medication including opioids to achieve patients' satisfaction.2.8.Six cytokines, including interleukin (IL) 1,6,17, tumor necrosis factor (TNF α), interferon (IFN γ), RANTES, and C-reactive protein (CRP) were analyzed for a two-time point at admission and discharge for each study group. Quantified human ELISA kits were purchased from R&D systems . Analyses were performed according to the manufacturer's protocol for each ELISA kit, assayed in triplicate, and read on a Molecular Devices microplate reader at 450 nm . Standard curves and individual good concentrations were determined using the Softmax 2.34 software. To keep experimental values within the linear region of the standard curves, samples were diluted from 1:5 to 1:100 as necessary for stimulated culture samples.2.9.Blood samples for cytokine and CRP analysis were collected through venipuncture at the admission and discharge. The collected blood samples were transferred to Eppendorf tubes and placed on ice during transport to the laboratory. Following centrifugation of the samples at 1,500 rpm for 10 min at 4°C, the serum was carefully collected from each sample and stored at −80°C until the analysis.2.10.All CT scan examinations were performed at 3-month postoperative period using a multi-detector computed tomography scanner. No specific patient preparation was required apart from quiet breathing. Patients were scanned in a supine position. The scan started below the diaphragm and ended at the supraclavicular regions. Cardiothoracic surgeon and radiologist conducted an analysis of CT scans from patients with chest reconstruction or wires. Axial slices were analyzed using a point quantitative scale  as previously described , 20, 21.2.11.χ2) or Fisher exact tests for variables with small numbers) and t-tests for continuous variables. Multivariate analyses were performed by using a stepwise logistic regression, in which all variables with a p-value of less than 0.10 in the univariate analyses or that were thought to be related to chest pain from the literature were included in the initial full models. A p-value of less than 0.05 was considered significant.Statistical analyses were performed with SPSS 11.0 software . Univariate analyses were performed for all relevant categorical variables by using contingency tables . All patients were presented with primary cardiac surgery. For patients in group 1 chest reconstruction was a secondary procedure after cardiac surgery. Twenty-six patients (61.9%) had undergone coronary artery bypass grafting, 6 (14.2%) had valvular procedures and 8 (19%) had aortic surgery. There were no significant differences between groups in terms of possible preoperative risk factors such as diabetes mellitus, chronic obstructive pulmonary disease, hypertension, tobacco usage, BMI, and immunosuppressive state. Among psychosocial factors patients with mediastinitis had a higher percent of anxiety and pain history. Clinical characteristics and postoperative variables of the patients are presented in p > 0.05). The mean hospital stays for groups 1, 2, and 3 were respectively 11.5 ± 5.42 days, 6.42 ± 1.39 days, and 6.5 ± 0.94 days (p = 0.0022). The data demonstrate the significant difference in the dose of opioids received by patients in ICU in the mediastinitis group compared with no infection groups (p = 0.0004). However, this difference disappeared when the patients moved to the surgical ward after the procedure (p > 0.05). At 3 months post-surgery four patients (3 in the third group and 1 in the first group) confirmed that they were still taking Oxycodone 5 mg once a day. Nine patients in group 1 received Oxycodone before admission to the hospital.Among 42 patients, there were 27 males and 15 females; the mean age of patients was 67 ± 2.45 years. There was no significant difference in demographic characteristics between the subjects in all groups. Forty-four percent of all patients were with body mass index (BMI) of over 30 kg/m3.2.All 14 patients with deep sternal infection (mediastinitis) were accepted and treated in our institution. The time between the primary surgery date and the onset of inflammatory symptoms ranged from 3 to 11 days. Surgical wound cultures were positive in all cases. Deep sternal infection was caused by a marked inflammatory response characterized by clinical symptoms like as fever, chest pain, sternal instability, draining of purulent secretion, widening of the mediastinum on chest x-ray, isolation of the microorganism in the culture of mediastinal tissue, or blood, and a marked rise in circulating cytokines and C reactive protein in serum. After chest reconstruction surgery clinical symptoms gradually declined, and on discharge day all patients fully recovered .3.3.p < 0.001). The intensity of initial postoperative pain varied significantly between the groups. On the day of discharge, the mean pain score at rest had decreased to 4.78 ± 1.12, 3.92 ± 1.07, and 5.85 ± 1.35 in groups 1, 2, and 3, respectively . Interestingly, the results on the day of discharge, one month, and three months follow-up indicated that the pain score for the patients was higher in group 3 with no infection and regular sternal closure  but not in the group with the previous inflammatory process with deep sternal infection as expected. The same trend was observed for the pain score during movement. Pain intensity during moving was higher, especially on day 1 and day of discharge. A significant difference was found between groups 2 and 3 at three months follow-up . The assessment of chronic pain at the three months follow-up demonstrated that in groups 1 and 2, patients had only mild pain. In group 3, three out of 14 patients had moderate pain (score 4–6), and others (5 patients) had mild pain (score 1–3). Thus, overall, 14 out of 42 patients have mild and moderate chronic pain 3 months after surgery. The intensity of pain in mediastinitis patients significantly decreased at the three-months after chest reconstruction and it was lower than in patients with regular chest closure and no infection.The assessment of the incidence and intensity of chest pain at 3 months post-surgery demonstrated that 14 out of 42 patients across all groups still experienced chronic pain. Specifically, in group 1 with sternal infection five patients had pain, while one patient experienced pain in group 2, and eight patients in group 3. Pain scores for each postoperative period at rest and during movement are displayed in 3.3.1.Patients with chest wall reconstruction and conventional closure in all three groups had almost the same hazard ratio (0.75) for development severe pain in all time points post-surgery. However, regarding chronic mild-to-moderate pain in the third group with conventional closure and no chest inflammation, patients the probability increased three times more (0.25) 3-month point after cardiac surgery.3.4.p < 0.0001) in deep sternal infection patients. While baseline levels of all cytokines were increased among patients who have developed a sternal infection, at discharge only the level of interleukin 6 remained significantly higher compared to no infection groups . Regarding the second and third groups with no infection, the baseline and discharge values of cytokines were comparable without any significant differences (p < 0.001). However, at the discharge time point, we did not find significant CRP differences between groups.Of the cytokines examined, all variables showed a significant relationship to the occurrence of sternal infection initially. It is consistent with severe inflammatory reactions due to mediastinitis. At baseline, we found a significant difference between the mediastinitis group (group 1) and groups with no infection . The median values of serum cytokines: IL 1,6,17, TNFα, IFNγ, and RANTES were significantly raised (ferences . C-react3.5.p < 0.0001) and a higher percentage of patients with evidence of complete sternal union   we found better sternal healing scores at 3-month follow-up  . In-grou< 0.001) .4.In this study, we investigated chronic pain after cardiac surgery and its relationship with sternal infection and chest reconstruction technique. Our finding showed that 14 out of 42 patients still experienced chronic pain at 3 months post-surgery, with more patients experiencing pain in the group with no infection and conventional sternal closure than in the group with mediastinitis and chest reconstruction. Additionally, we found that cytokines were significantly related to the occurrence of sternal infection initially, with interleukin 6 levels remaining significantly higher in patients with sternal infection compared to those without infection. Also, we found a difference in ICU time between groups 2 and 3, with group 2 patients having a longer ICU stay. However, statistical analysis revealed that the difference is not significant. We believe that this lack of significance may be attributed to the fact that conventional sternal closure (group 3) is a widely accepted procedure that ICU doctors are very familiar with. In contrast, chest wall reconstruction is a relatively new technique, and doctors may have provided extra care to these patients. We did not observe any surgical or other complications between these groups.Chronic pain after cardiac surgery is a significant issue characterized by allodynia and hyperalgesia, indicating its neuropathic origin. Post-surgery pain is subjective sensation, and every patient may experience it differently, depending on the type and severity of the procedure, anesthesia, physiological, and psychological factors , 23. AnxOur study found that pain levels were higher on discharge day than later follow-up, and 14 out of 42 patients experienced persistent mild-to-moderate pain three months after cardiac surgery. It is consistent with previous research , 5, 10. Cytokines play a critical role in initiating and maintaining inflammatory processes , and in This study provides evidence that sternal reconstruction offers significant mechanical benefits, leading to better bone healing, reduced acute and chronic thoracic pain, and less need for opioids in the early postoperative period. Traditional surgical techniques allow for movement and separation of the sternal halves, which decreases the stability of sternal closure. The presence of sternal nonunion and movement may increase pain, which can impact recovery, respiratory function, mobility, and patient activity.4.1.This study had a limited sample size for the group with mediastinitis due to the low incidence of deep sternal infection after cardiac surgery, and it was challenging to identify high-risk patients who matched the inclusion criteria. The confidence interval was not calculated to determine the expected prevalence when extrapolated to the entire population, and a multivariable logistic regression analysis was not conducted. Additionally, it would be beneficial to have a follow-up period of more than three months to gain a more comprehensive understanding of the outcomes.5.The study's findings suggest the following: (a) among patients who underwent cardiac procedures with sternotomy, 14 out of 42 had chronic thoracic pain three months after surgery. However, in patients with previous sternal infection, only 5 out of 14 had pain, while 8 out of 14 of patients had pain after regular chest closure without infection, (b) the incidence and intensity of pain can be influenced by the surgical technique used for chest reconstruction, (c) treated mediastinitis does not appear to be a determining factor in the development of chronic chest pain, (d) except for interleukin 6, there is no correlation between cytokine levels and pain scores, even though interleukin 6 remains elevated for a long time after treatment, e) One of the significant strengths of the study is that it found a strong correlation between sternal bone healing and postoperative chest pain. The study's authors believe that further research that includes molecular and genomic factors is necessary to provide a more comprehensive evaluation of chronic chest pain after cardiac surgery.


In the Emergency Department (ED), pain is one of the symptoms that are most frequently reported, making it one of the most significant issues for the emergency physician, but it is frequently under-treated. Intravenous (IV), oral (PO), and intramuscular (IM) delivery are the standard methods for administering acute pain relief. Firstly, we compared the safety and efficacy of IN analgesia to other conventional routes of analgesia to assess if IN analgesia may be an alternative for the management of acute pain in ED. Secondly, we analyzed the incidence and severity of adverse events (AEs) and rescue analgesia required. We performed a narrative review-based keywords in Pubmed/Medline, Scopus, EMBASE, the Cochrane Library, and Controlled Trials Register, finding only twenty randomized Clinical trials eligible in the timeline 1992–2022. A total of 2098 patients were analyzed and compared to intravenous analgesia, showing no statistical difference in adverse effects. In addition, intranasal analgesia also has a rapid onset and quick absorption. Fentanyl and ketamine are two intranasal drugs that appear promising and may be taken simply and safely while providing effective pain relief. Intravenous is simple to administer, non-invasive, rapid onset, and quick absorption; it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management. Acute pain is one of the most frequent symptoms in patients presenting to the Emergency Department (ED), deriving from various conditions, such as trauma, injuries, headache, renal colic, cancer, etc.Due to its heterogeneity, it frequently represents a challenge for emergency physicians, and data indicate that inadequate pain management is rather typical ,2.There are many medications that can be administered, moreover using different routes. The qualities needed in the drugs we want to provide in emergency care are quickness, effectiveness, and safety. The most common routes for acute analgesia are per os (PO), intravenous (IV), and intramuscular (IM). In patients who need quick analgesia or who may have a nihil per os condition, the per os (PO) route may not be the simplest to use. However, even the intravenous administration may not be very convenient because it requires the placement of a peripheral catheter; therefore, the patient must have good venous patrimony, and the hospital requires qualified personnel.On the other hand, IM administration frequently causes the patient discomfort. Additionally, the medication takes longer to absorb via muscle, delaying the beginning of the analgesic action.In this scenario, because of its safety, the simplicity of administration, the non-invasive route, the quick effect, and the fact that it does not require a peripheral catheter, the intranasal (IN) method has become increasingly popular . CurrentThe primary goal of the study was to compare the differences in pain scores between IN analgesics and active comparator or placebo from baseline to the time specified in the RCT. Adverse event (AE), frequency and severity, as well as the need for rescue analgesia (if available), were secondary outcomes.There is little published material regarding opioid IN administration. Due to their difficulty in taking oral or intravenous drugs, most of the studies were conducted on pediatric patients ,6. Few sTo our knowledge, there is only one review that takes a comprehensive look at the use of intranasal analgesia in emergency care and includes a small number of trials .Probably, the lack of studies is due to the poor habit of using drugs with this route, few devices to use, and poor staff training. In recent years, literature about the effectiveness of intranasal analgesia has increased.We conducted a literature review on the main databases, such as PubMed, the Cochrane Library, Medline, Embase, and Scopus in the timeline 1992–2022, using the keywords: emergency department, intranasal administration, analgesics, migraine, acute pain (MeSH Terms).We selected all the Randomized controlled trials (RCTs) published in English and evaluated the use of IN analgesia in Emergency Care.Only adult patients who had received at least one dosage of IN analgesia for acute pain in the Emergency Room and Prehospital Care were the only ones selected for these studies.The primary search found 126 results. Study protocols, duplicated results, not pertinent articles, and unavailability of full text were excluded. Finally, 20 clinical trials were included in this review , and theIn order to assess the effectiveness and impact of the analgesics, validated pain scales were utilized in every trial that was looked at. The frequency of AEs and the requirement for rescue analgesia were also considered by these scales. The inclusion criteria of the patients participating in the trials were as follows: only adults were selected, including patients receiving IN analgesia compared to OS, IV, or a combination of different routes. Pregnant patients were not allowed. Patients were also excluded if they had used analgesics within the previous hours or if they had hemodynamic or respiratory instability or disorientation. Patients who could not provide informed consent  were also excluded. Even patients who reported an allergy or an intolerance to the trial drug were ineligible.The sample needed for each RCT was calculated to obtain 80% or 90% statistical power.The results are summarized in As known, triptans are frequently used to treat acute migraine; among all, sumatriptan is one of the most used. The oral formulation is the most prescribed, although it has several limitations, such as absorption variation and onset differences that influence the efficacy. Triptans also have well-known side effects that may restrict their effectiveness and tolerability. Few studies have investigated the use of intranasal analgesia for migraine or headache in ED ,18,27.A study conducted by Meredith et al. (2003) involved acute migraine. They examined the pain relief using the Visual Analogue Scale (VAS) after the administration of IV Ketorolac versus nasal sumatriptan. The study found that while both medications decreased migraine-related pain, IV Ketorolac was more efficient. However, this study has several limitations due to the limited sample size and the lack of AEs recorded .Another trial examined the potential for IN Lidocaine to treat migraine; however, it was no more successful than placebo, even in addition to IV Metoclopramide . The second outcome of the trial was the requirement for rescue medication, which was IV Fentanyl. Patient pain severity was assessed using the Numeric Rating Scale (NRS). Nevertheless, local discomfort brought on by lidocaine may be a confounding factor in the patient’s perceived outcome .Benish et al. released the THINK Trial in 2019 with the aim of comparing the analgesia with IV metoclopramide and diphenhydramine vs. IN ketamine among patients with primary headaches in ED. All 56 of the patients they enrolled were adults. The VAS scale was used to assess changes in pain, and the results showed that standard medication was not superior to ketamine in the recruited patients. However, this RCT had several limitations. For instance, it was a single-blind trial, and patients in the control arm could have received IV Ketorolac or Dexamethasone in addition to the standard therapy, which could have influenced the comparison of analgesic effectiveness.Savari et al. (2022) compared IN ketamine to IV ketorolac; the group treated with IN ketamine had a greater reduction in pain intensity, but they also had more adverse effects such as fatigue, dizziness, discomfort, nausea, and hypertension .One of the most frequent causes of pain in ED patients is trauma, which frequently requires a combination of IM and/or IV drugs. Recently, there has been an increase in the use of IN analgesics .Shimonovic et al. (2016) compared IN ketamine to IV or IM morphine; despite ketamine has been well studied as an analgesic agent, the IN administration has recently been introduced in ED. Instead, there is a lack of knowledge on the use of morphine in the literature. They enrolled a sample of 90 patients and randomized them into three groups; all three groups showed a similar level of pain relief. The study shows that IN ketamine can be used as an analgesic in emergencies since it demonstrated efficacy and safety comparable to IV and IM Morphine, and no severe AEs were noted .Blancher et al. (2019) compared IN sufentanil versus IV morphine, assessing NRS at 30 min, with 4 h follow-up: they found some severe respiratory AEs (reporting a number needed to harm = 17), questioning the safety of this medication .Chew et al. (2017), in a small open-label study, compared IN fentanyl added to IV tramadol and metoclopramide, showing an improvement in VAS score at 10 min, with transient side effects such as lowering in blood pressure and dizziness .In 2019, performed a clinical trial on adult patients with isolated limb injuries, Lemoel et al.  examinedTongbua et al. (2022) recently showed non-inferiority of IN ketamine compared to IV morphine for acute musculoskeletal pain in the elderly, with a quick and sustained effect (up to 120 min), without a significant difference in AEs .In the Emergency Department, renal colic is a common cause of abdominal discomfort that frequently requires a combination of analgesics, such as non-steroidal anti-inflammatory drugs and opiates; one of the most used is ketamine. In fact, numerous randomized trials have compared IN therapies to IV analgesia .Farnia et al. (2017) compared IN ketamine to IV morphine, observing a statistically significant reduction in pain score, although the small sample size suggested the need for larger studies .This conclusion was also supported by the study conducted by Pouraghaei et al. in 2021, which examined these two drugs showing comparable pain relief efficacy in renal colic and no relevant adverse effect .In another study, Desmopressin was suggested as an alternative to the most often-used medication. The study compared Indomethacin alone versus Indomethacin with IN Desmopressin for the management of renal colic pain. However, Jalili et al. did not find IN Desmopressin to be more efficient than Indomethacin alone when compared to IN Ketamine .In a comparison between IN Ketamine and IV Fentanyl, Mozafari et al. 2020) discovered that ketamine was less efficient than fentanyl and was more likely to cause side effects [20 discovNazemian et al. (2020) compared IN to IV fentanyl added to IV ketorolac. They found IN fentanyl effective in pain control, though significantly less than IV fentanyl; they concluded that this option could be considered in situations where obtaining an IV route could lead to a delay in pain control, such as overcrowded ED .To our knowledge, two RCTs have assessed IN analgesia in a prehospital setting.Rickard et al. (2007) compared IN fentanyl to IV morphine, demonstrating a similar VAS reduction without a significant difference in AEs; a limitation of this trial was the lack of blindings .Andolfatto et al. (2019) compared IN ketamine to a placebo when added to standard care (Nitrous Oxide), finding an improvement in pain control without severe AEs .A high percentage of cancer patients experience physical pain, which is frequently a chronic discomfort that ranges from moderate to severe. Breakthrough pain is a term used to describe the exacerbations of this type of pain that often occur in patients who are already receiving analgesic treatment, including opioids.Considering the challenges associated with getting a venous route in cancer patients, IN analgesia may be helpful in treating cancer patient’s pain.Unfortunately, there are few clinical studies of analgesic therapy for cancer patients in ED.Only one small non-inferiority open-label RCT  compared IN fentanyl to IV hydromorphone in patients presenting at the ED with severe breakthrough cancer pain. Two out of three evaluations recommended the use of IN Fentanyl, which also has the benefit of requiring less time to administer. However, due to a protocol deviation  and lack of blinding, this trial was conducted without knowing the actual pain score at baseline. This RCT might have an important bias .Sin et al. (2019) compared IN sufentanil to IV morphine in the treatment of abdominal and low back pain, finding equal improvement in NRS and AEs; the study’s limitations include a small sample size and lack of data on IV morphine rescue analgesia .Pain control is universally considered an important issue, especially in ED patients; because pain affects a patient’s quality of life, it is crucial to obtain the right treatment. Despite the availability of multimodal medications, analgesic therapy is frequently insufficient .IN fentanyl and ketamine have already shown their safety in pharmacokinetics trials. These drugs have a higher bioavailability thanks to their fast absorption via the nasal mucosa and the lack of first-pass effect. It is important to remember IN route restrictions like pathologic changes to the nostrils and a limited amount of administrable volume ,31,32.Although there are limited trials available in the ED context, the potential benefits of IN therapies, such as rapid and simple administrations with prompt absorption, may improve pain control in ED and prehospital settings. Subdissociative doses of ketamine were proven to be safe and helpful in patients out-of-hospital, too, by a retrospective large-sample trial .Low-dosage ketamine analgesia in patients with severe acute pain is becoming more and more promising due to its analgesic efficacy (similar to opioids), the potential to maintain circulatory stability and respiratory reflexes, and neuroprotection in patients with acute brain damage ,35,36.Opioids are being used extensively to treat acute pain, although they can have side effects that vary on dosage, including weakness, dizziness, nausea, and constipation. Due to this, the importance of multimodal analgesia with opioid-sparing techniques should be considered, especially considering the worrying data about opioid abusers. Ketamine appears to be useful in lowering the demand for opioids ,38. Due IN route may help for severe pain requiring quick management (such as trauma or breakthrough cancer pain). The bioavailability of IN opioids depends on the specific molecule, being rather high for fentanyl and sufentanil, thanks to their lipophilic structure ,41,42.Regarding the safety profile, most AEs recorded were moderate and did not need medical intervention. According to the literature, dizziness was the most common. Confusion, a brief drop in blood pressure, nausea, and vomiting were also usual AEs. A small percentage of patients receiving opiate-based treatment also occasionally experienced transient bradypnea or oxygen saturation below 90%, necessitating a short-time administration of oxygen therapy. Only a minor number of serious AEs were observed in a few trials .For patients presenting with headaches, IN ketamine was found to be more effective than IV ketorolac despite a higher prevalence of side effects ,8,9,10.When compared to IV morphine for the treatment of pain due to traumatic injuries, IN ketamine demonstrated a non-inferiority effect; in fact, ketamine has a morphine-sparing effect. Early IN Sufentanyl administration (after triage) can enhance pain management and reduce the need for IV analgesia. For this, adding IN Fentanyl to IV Tramadol resulted in a higher decrease in pain score after 10 min. Only one research reported some significant AEs when IN Sufentanyl was compared to IV Morphine ,17. HoweIn small research, IN ketamine was found to be more effective than IV Morphine for patients with renal colic; another trial revealed that IN ketamine and IV morphine were equally beneficial. Although IN fentanyl was proven to be less efficient than IV fentanyl, it may still be used when placing a venous catheter, which could be difficult  ,21,22,29Given that prehospital treatment is sometimes provided by paramedics, who are only trained to administer certain medications, IN analgesia may aid in the quick delivery of pain relief in this scenario. There is not much research regarding this in the literature, but in this case, IN fentanyl was found to be just as effective as IV morphine, while IN ketamine led to the fastest onset in pain relief ,24. A reThese findings suggest that it might be a viable choice in a variety of situations to reduce patient suffering or delays in pain management or when accessing an intravenous route may be challenging due to clinical circumstances or a shortage of qualified healthcare professionals. In particular, in busy EDs, a standardized protocol for early analgesic administration may aid in pain treatment.Analgesia needs to be tailored to each patient’s features, type of pain, and clinical environment. IN Fentanyl and Ketamine look promising and may be administered easily and safely while providing effective pain relief.For this review, we could not find randomized trials including patients presenting with alteration of mental status and respiratory or hemodynamic instability, probably because of the potential impact of narcotics on breath or arterial blood pressure; none of the studies included pregnant women.This could be a major limitation, considering that in Emergency Care, pain and respiratory or hemodynamic instability often coexist.The absence of follow-up in this evaluation (just one research included a follow-up at 48–72 h) makes it impossible to determine if these patients need additional medications in the hours or days that followed or the frequency of subsequent adverse events (AEs). The fact that patient recruitment was completed only when researchers were available and without knowledge of the full population and the characteristics of patients who presented with pain to the ED raises the possibility of bias.Some of the trials included were conducted on a small sample. There were few studies from Europe and Oceania; most trials were conducted in Asia or America, and no trials were undertaken in Africa. Only a small number of RCTs from Iran included patients who were 15 years old or older, whereas all the other studies included participants who were 18 years old or older. The risk of local irritation or side effects, as well as the comparison of the IN medication to placebo with a difference in pain control following the injection of analgesic or saline solution, were other possible sources of bias. In some cases (such as breakthrough cancer pain), only open-label trials were found .Moreover, an optimal rescue therapy or analgesia could help hospitals out with the never-ending issue of overcrowding ,45.