Chronic pain is one of the most frequent clinical problems after inguinal hernia surgery. Despite more than two decades of research and numerous publications, no evidence exists to allow for chronic postoperative inguinal pain (CPIP) specific treatment algorithms.This narrative review presents the current knowledge of the non-surgical management of CPIP and makes suggestions for daily practice.There is a paucity for high-level evidence of non-surgical options for CPIP. Different treatment options and algorithms have been published for chronic pain patients in the last decades.It is suggested that non-surgical treatment is introduced in the management of all CPIP patients. The overall approach to interventions should be pragmatic, tiered and multi-interventional, starting with least invasive and only moving to more invasive procedures upon lack of effect. Evaluation should be multidisciplinary and should take place in specialized centres. We strongly suggest to follow general guidelines for treatment of persistent pain and to build a database allowing for establishing CPIP specific evidence for optimal analgesic treatments. Within the past decades, chronic postoperative pain has gone from sporadically reported, to being recognized as a common and complex problem after all types of surgery. Whereas the overall incidence ranges from 5 to 20% depending on the specific procedure, pain affecting everyday activities occurs in about 5–8% of patients across procedures –3. The GChronic postoperative inguinal pain (CPIP) is defined as pain for at least 3 months, including a level of pain rated by the patient as at least moderate and impacting daily activities . Since gThe optimal solution for CPIP would be prevention. However, despite several intra-operative strategies , it is still impossible to avoid CPIP from occurring in specific patients. This is partially due to inpatient factors, such as patient’s genetics and nociceptive systems, making them susceptible to chronic pain. Thus, we as clinicians are left with the task of managing CPIP, which is difficult due to its complexity and heterogeneity, and the lack of clear evidence based guidelines.Several approaches have been suggested for the management of CPIP, ranging from cognitive therapies or pharmacological interventions to re-operations with neurectomy and/or mesh removal. Treating CPIP with another surgical intervention sounds contradictory on itself, as surgery for pain could potentially aggravate pain. The essence is “do no further harm” or “doing less is best”. However, reoperation can produce significant improvements and is undoubtedly an effective treatment modality in selected patients , 11.The management of patients with CPIP is complex, and we have to acknowledge that the evidence is still too sparse to allow firm recommendations for daily practice. Currently, studies on surgical interventions for CPIP have inadequate descriptions of preoperative triage processes to make firm conclusions on the actual risk/benefit profile relative to less invasive measures. Nevertheless, promising results are emerging and evidence from other areas within chronic pain can be drawn upon when treating these patients. The aim of this review was to present the current knowledge of the non-surgical management of CPIP, in the context of social, psychological and physical factors of the individual patient. Additionally, suggestions are made for the management of patients with CPIP and future research.For this narrative review we were informed by studies that describe the non-surgical management of CPIP. We searched seven electronic databases . The following search terms were used: “inguinal hernia”, “groin hernia”, “hernia repair”, “mesh repair”, “CPIP”, “pain”, “inguinodynia”, “non-surgical treatment”, “capsaicin”, “lidocaine”, “pharmacological”, “radiofrequency”, “cryoablation”, “peripheral nerve stimulation”, “DRG”, “centralization”, “expertise”. All titles and abstracts were screened for eligibility by two authors . In case of disagreement the other authors were consulted. Based on the literature and on personal experience suggestions were made.Understanding the problem of CPIP renders a clear definition first. Throughout literature the definition of chronic postsurgical pain differs. The original definition of postsurgical pain by Macrae stipulates that the pain has developed after a surgical procedure. Furthermore, the definition includes at least two months duration, and that other causes for the pain as well as other pre-existing problems must have been excluded or solved . AccordiA time threshold of three months has been suggested by IASP because it provides for clear operationalization . HoweverDespite the various definitions of chronic pain, the Hernia Surge guideline recommends using the widely accepted time period of at least three months to define CPIP, and we agree with that . AdditioGuidelines have gained much popularity in the last decades, by summarizing the best available evidence and providing recommendations for physicians. They will hopefully become more specific for CPIP in the future, when more evidence is gained, but as for now they are mainly overviews of topics that recommend more research.Table Although limited evidence exists for systemic pharmacological treatments , a step-wise multidisciplinary approach starting with minimally invasive measures like systemic analgesics is advocated in the seven reviews and the Hernia Surge guideline . AlthougBased on two small studies, lidocaine and capsaicin patches have not been proven to be effective in CPIP patients , 23.Nerve blocks are another option in the management of CPIP that are advocated in all reviews, algorithms and the Hernia Surge guideline . AlthougIn addition to the conventional nerve blocks, there is evidence on the diagnostic value of trigger point infiltrations . These lAll studies on more invasive conservative treatment modalities for CPIP (e.g. ablation techniques and neuromodulation) have significant limitations, such as small-volume studies, non-controlled and non-randomized designs, short follow-up periods and no report of adverse events or complications –35. In aIn the Hernia Surge guideline it was already stated that there is a paucity of non-surgical options for CPIP. Despite many research questions that were raised, relatively few new insights were published in past decade. In future studies the role of trigger point infiltrations needs to be studied and clearly differentiated from peripheral nerve blocks. Additionally, it is suggested that the repetitive effect of more proximal nerve blocks in managing CPIP is explored. Furthermore, the role of central sensitization needs to be studied.Due to the lack of established evidence-based treatment options for CPIP, we suggest to apply the following strategy for handling CPIP:Information: The patient assessed for a first-time hernia repair should be advised that there is a about 10–12% risk of persistent pain at three months follow-up and a 0.5–6% risk of pain affecting everyday life at one year follow-up, including sexual function [function . The disfunction . The patfunction , 38. TheAssessment: As for now we suggest that patients with CPIP are referred to dedicated hernia expert centres that should collect core data in a standardized manner to allow for combining these later on with other centres [ centres . This wiHistory: As with any chronic pain patient the first approach should be to gather fulfilling information on the surgical and pain history of the particular patient, including previous treatment attempts and results. The intensity, frequency and impact of pain on everyday activities and sexual life should be registered, using validated questionnaires such as the activity assessment scale [nt scale . Additiont scale .Physical examination: A physical examination should be performed, describing the painful area including the surgical scar, surrounding skin, genitalia for testicular affection in particular, contralateral side, other potential differential causes . These may include radiological investigations, and effect from diagnostic nerve blocks or trigger point infiltrations [trations .Sensory examination: Assessing the occurrence of sensory disturbances such as hypoesthesia, hyperalgesia, allodynia, etc., should be performed in a standardized but everyday clinical feasible way. The precise methodology is not agreed upon, but a relatively simple bedside testing protocol has been suggested with good agreement with the far more elaborate and time consuming Quantitative Sensory Testing methodology (QST), i.e. with cotton swaps, finger pressure, etc. [re, etc. . The sugre, etc. , as in ore, etc. , but recre, etc. .3.Treatment: Based on all literature it is clear that we have not yet formed solid evidence to give specific recommendations on the treatment of CPIP patients [patients . Despitepatients . On the patients , 47. Thupatients , 49. Howpatients  and is oThird line treatments include (repeated) nerve blocks and trigger point infiltrations, whereas cryoablation and pulsed radiofrequency are still considered with low evidence for efficacy requesting further evidence. For patients without satisfactory effect, we believe that the possibility of re-operation with  mesh removal and/or neurectomy can be discussed, but lies outside the scope of this review.4.Evaluation and follow-up: Regardless of the specific treatment chosen in the various steps described above, we consider it pivotal that follow-up should be standardized regarding assessment and time, with defined success criteria for continuation of treatment or initiation of other options. These also include assessing the side-effects from pharmacological treatments such as dizziness, cognitive impairment and potential abuse.Any hernia center should have a formulated policy for how to deal with the inevitable occurrence of CPIP. These include preoperative information of the patient on the risk, assessment of CPIP during postoperative follow-up including use of analgesics (opioids and gabapentinoids in particular) and established collaboration and referral to expert pain centres ideally with an interest in CPIP and/or other chronic postoperative pain syndromes.Since there is a paucity of high-level evidence on best practices, more evidence needs to be created. Additionally, low-level evidence needs validation.One of the major challenges in the data on both non-surgical and surgical interventions is the selection of patients in the individual trials. The scarce descriptions of any actual effect of previous interventions, as well as the lack of potential effects of less invasive interventions in the included patients, limits the ability to place the individual therapies in a rational staggered approach. This can only be solved by creating well-defined inclusion data and follow-up between interventions, ideally even standardizing the order of interventions.Due to the scarcity of evidence, we suggest that a database including all treated patients is created. This can be a database on the local, national, or international level. Ideally a centralized database is created with core data collected at all sites, allowing merging of information and multicentre studies for large trials or in cases of rare patient findings. Such a database structure should also allow for individual centres to add local investigations and treatment strategies but informing about this as to make sure data are comparable. The database should not apply to research projects only, but collect data from all treatments being performed at the participating centres. It is crucial that all CPIP patients treated in these centres are included in this database to avoid selection bias. We suggest that the hernia-surgery community formulates an assessment algorithm with standardized treatment suggestions similar to the approach described above. This will allow for large data on specific treatment strategies regarding efficacy and side effects, as we believe the time has come to move away from the predominantly small single-centre studies. Besides describing the effect of the individual interventions, such a database will also allow the relative effects to be assessed, facilitating the establishment of an evidence-based treatment order of invasive interventions, optimizing benefit and minimizing harm. Formulating such an algorithm will undoubtedly be an advantage, also to local centres not participating, due to the constantly updated evidence-based best-practice being formulated.Last, we suggest that the optimal management of CPIP patients should be centralized in regional, specialized hernia centres. Since the volume of hernia surgery in expert hernia centers reports lower incidences of CPIP, the treatment of CPIP patients should ideally be centralized as well. The management of CPIP has been proven to be very challenging, requiring a multidisciplinary team approach with dedicated professionals. Establishment of such expert centres forms the basis for creating evidence-based treatment algorithms for CPIP patients and initiating the databases mentioned before. We believe this is pivotal for the success of CPIP treatment in the future.It is difficult to draw conclusions on the management of CPIP given the scarcity of high-level evidence in this field. Literature has various definitions of CPIP; studies show heterogeneity of study populations and study cohorts are relatively small. This impacts the generalizability of results, limiting the applicability of study results in new CPIP patients.CPIP is one of the most frequent clinical problems after inguinal hernia surgery and despite more than two decades of research and numerous publications, no evidence exists to allow for CPIP specific treatment algorithms. We suggest that non-surgical treatment is introduced in the management of all CPIP patients. The overall approach to interventions should be pragmatic, tiered and multi-interventional, starting with least invasive and only moving to more invasive upon lack of effect. Evaluation should be multidisciplinary and should take place in specialized centres. We strongly suggest to follow general guidelines for treatment of persistent pain and to build a database allowing for establishing CPIP specific evidence for optimal analgesic treatments.


N = 90). Group, sex, and group-by-sex interactions were analyzed via repeated measures analysis of variance. Among HC, males exhibited significantly greater blood oxygen level dependent (BOLD) signal in the striatum during reward anticipation, particularly during large reward trials. By contrast, no significant sex differences were observed among patients. A significant group-by-sex interaction was also observed, revealing diminished BOLD responses among males with chronic pain relative to control males. These results provide novel evidence of sex-specific reductions in anticipatory responses to reward in patients with chronic pain. Altered striatal reward responsivity among males, but not females, suggests that the reward systems of males and females are uniquely disrupted by chronic pain, and highlights the value of including sex as a factor of interest in future studies of reward responsivity in the context of persistent pain.Chronic pain and reward processing are understood to be reciprocally related to one another. Previous studies of reward processing in chronic pain patients have reported incongruent findings. While several factors likely contribute to these disparate findings, these previous studies did not stratify their analyses by sex—a factor previously shown to robustly impact reward-related responses. Thus, we examined sex as a factor of interest in level of striatal activation during anticipation of monetary incentives among patients with chronic non-specific back pain and healthy controls (HC). This study utilized functional magnetic resonance imaging during a monetary incentive delay task to evaluate reward and loss responsivity in the striatum among males and females with and without chronic pain ( Chronic pain is an exceedingly common health condition impacting 1 in every 5 adults in the United States . Sex-speChronic pain, emotional processing and responding, and reward processing are regulated by overlapping brain regions, including core regions within the mesolimbic dopamine pathway like the ventral striatum . ActivitWhile studies on this topic in humans are still limited, the current body of research suggests persons with chronic pain may exhibit dysregulated reward-related activity ; howeverSex differences in the reward system have been repeatedly observed previously. In humans, positron emission tomography research has shown dopaminergic activity in the ventral striatum following amphetamine  and nicoThe present study aims to build upon and clarify mixed findings of ventral striatal activity during reward anticipation from This study included participants recruited from the University of Michigan as part of two parallel studies utilizing the MID task to explore reward-related processing in HC and chronic pain patients. A total of 97 participants successfully completed the MID task. Four subjects were excluded for excessive motion [> 20% volumes exceeded the 0.5 mm framewise displacement (FD) threshold] and 3 subjects had other functional data abnormalities; accordingly, 90 participants were left for analysis: 50 HC participants  and 40 CNBP patients . Sex was self-reported as that assigned at birth and was not distinguished from gender.via advertisement. Patients were recruited from a local pain clinic and had a history of at least 1 year of chronic, non-specific back or neck pain; these participants self-reported pain levels of 3–8 on a 0–10 verbal rating scale. Additionally, CNBP participants did not endorse lifetime substance dependence, current nicotine dependence, or regular use of medications that had known central nervous system activity.All participants provided written informed consent prior to study procedures, and all study protocols were approved by the University of Michigan’s Institutional Review Board. All participants were right-handed adults. HC had no history of psychiatric disorders and were recruited via button press to a target in order to win or avoid losing money. During each 6 s trial, participants were presented with a series of cues indicating which type of incentive was at stake. This was followed by a fixation cross , during which individuals anticipated being able to work for a reward or avoid a loss. Then, participants were presented with a response target, to which they were instructed to respond as fast and accurately as possible in order to successfully win or avoid losing money. Immediately following the target, participants received feedback on their performance. The task was adjusted to ensure approximately 66% accuracy.The MID task was selected for use during fMRI as way to assess neural representations of reward processing. When examining neural activity during anticipation of reward and loss, this task is known to robustly recruit the ventral striatum . The MIDThe MID task was presented using Eprime . All subjects participated in two consecutive MID runs, each consisting of 70 pseudo-randomized conditions from the following condition types: large, medium, and small rewards , large, medium, and small losses , and neutral (±$0).Whole brain functional images were acquired on one of two General Electric scanners: a 3T Signa Excite II System or a 3T Discovery MR750 System. T2*-weighted images were collected . Two sessions of 210 volumes were acquired and analyzed. Structural images were acquired for anatomic normalization using T1-weighted, 3D inversion recovery-prepared fast spoiled gradient recalled sequences see .All neuroimaging data were preprocessed using fMRIPrep  version 1.3.0.post3 . Data weAn individual task model for each participant was constructed using a general linear model within SPM12. First level models included parameters of interest corresponding to the anticipation of each condition type, modeled as impulse functions following presentation of the 2,500 ms fixation cross and six head motion parameters . Volumes with excessive motions (FD > 0.5 mm) were included as confounds in the model . To accoa priori region of interest (ROI) approach to explore differences in BOLD signal among CNBP patients and HC. We focused on the ventral striatum due to previously discussed divergent results   . We calcEmotional states were measured among a subset of individuals immediately prior to the fMRI scan. State affect was measured using the Positive and Negative Affect Schedule (PANAS) —a 60-itet-tests, univariate analysis of variance, and repeated measures analysis of variance. Associations between BOLD signal and psychophysical measures were computed with two-tailed Pearson correlations, calculated separately for males and females.All statistical analyses were conducted using IBM SPSS 26 . Comparisons between groups were performed using F = 2.6, p = 0.06]. See Baseline characteristics of CNBP patients and corresponding HC participants are shown in F = 4.04, p = 0.11]; specifically we observed a significant main effect of group , with patients endorsing higher levels of negative affect than controls. Similarly mean differences were noted in PANAS positive affect , with a significant group-by-sex interaction  showing female controls endorsed the highest levels of positive affect and female patients the lowest, while male patients and controls endorsed nearly identical levels of positive affect. We also observed significant differences in POMS Total Mood Disturbance (POMS-TMD) scores , with a significant main effect of group , demonstrating patients reported significantly greater levels of mood disturbance than controls. Finally, we also noted significant differences in state anxiety , with a significant main effect of group  indicating greater rates of state anxiety among patients relative to controls.There was a significant difference in mean PANAS negative affect scores , but females trended toward greater pain intensity than males. Female patients also endorsed higher levels of current back pain unpleasantness, though these ratings were again not significantly different from males .Two-sample tests between patient males and females did not reveal any differences in clinical back pain intensity as measured by the McGill Pain Questionnaire  was also observed, with HC collapsed across sex exhibiting significantly greater ventral striatal activity than CNBP participants, particularly during reward trials  = 15.58, p < 0.001; Post hoc analyses revealed males collapsed across group, relative to females collapsed across group, exhibited significantly greater BOLD signal during anticipation of large incentives (p = 0.02); this trend was also observed for medium and small incentives, though differences were not statistically significant. Mean ventral striatal BOLD signal comparisons between group and sex are reported in A significant valence-by-group interaction [d trials . These fr = 0.43, p = 0.04); however, this was non-significant among males   . No signThe present study provides the first evidence that biological sex appears to significantly impact neural responses to reward anticipation among chronic pain patients. This research builds upon and clarifies conflicting results from two previous studies examining BOLD signal among chronic pain patients and pain-free controls during a MID task see , and higIn a sample of CNBP patients and HC, we show that ventral striatal BOLD signal was significantly lower among CNBP patients relative to HC participants during anticipation of reward—particularly during large reward trials—and that this effect is uniquely observed between patient and control males. The fact that significant findings are more pronounced during larger reward trials is perhaps unsurprising, as previous research shows ventral striatal activation during anticipation of reward corresponds to the salience and magnitude of an incentive . Our obsMales and females exhibit vast differences in clinical experiences of chronic pain. Chronic pain is more prevalent among females than males overall, and within specific chronic pain syndromes, including back pain . In geneVentral striatum alterations in reward responsivity in preclinical models yield insight into neurobiological alterations in chronic pain. Sex differences in the neural mechanisms underlying reward and associated behavior have been repeatedly observed in rodents, which is likely in part a function of gonadal hormones . For exaSex differences in reward processing among healthy humans are similarly well documented. For example, Given that reward system dysregulation is a prominent feature of the neurobiological underpinnings of chronic pain, it is somewhat surprising that well established sex differences in reward processing seem to disappear in the context of chronic pain. Our finding that reward responsivity within the ventral striatum is altered in males while stable among females suggests (1) that chronic pain-related reward system alterations in males hinge more on ventral striatal responsivity than in females, and (2) that prototypically heightened reward responsivity to monetary incentives in males is possibly more vulnerable to disturbance by chronic pain. Meanwhile, given the positive association of ventral striatal BOLD signal with pain intensity scores uniquely observed among females, it may be that individuals who more effectively downregulate ventral striatal responses to reward anticipation are also more effectively regulating pain. Thus, it could also be the case that reward processing in females is equally vulnerable to disturbance by chronic pain, yet in contrast to males, this is due to less effectively downregulating ventral striatal activity.Our findings in females complement those of The present study provides novel evidence of sex-specific reductions in anticipatory responses to reward in patients with chronic pain. These findings hold valuable implications for future mechanistic studies of chronic pain, particularly regarding the extent to which medications commonly used to treat chronic pain  may differentially alter both neurobiological and behavioral sequelae among males vs. females. Indeed, a few studies that have evaluated brain reward processing in patients with chronic pain who take opioids show altered frontostriatal responses to reward  and alteA few limitations should be noted in consideration of these results. In addition to the limitations imposed by our inability to account for contributions of menstrual cycle phase and gonadal hormones, our findings were derived from a relatively small sample. Moreover, our recruitment from specialized pain clinics may reduce the generalizability of results. Additionally, these results are cross-sectional. Future studies with larger, more heterogenous samples will allow for more nuanced examinations of causal effects and aid in unpacking the unique contributions of psychological, endocrine, and neurobiological variables to sex differences in reward anticipation among chronic pain patients. Menstrual cycle tracking and blood collection for hormone monitoring will also be essential additions to future studies. Finally, given the statistically significant difference in age between groups, further research is needed to explore, rather than control for, the impact of aging on reward valuation. Despite these limitations, the present study contributes innovative findings to the small existing body of literature exploring striatal hypofunction in chronic pain.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the University of Michigan Internal Review Board. The patients/participants provided their written informed consent to participate in this study.TL and J-KZ were responsible for the study concept and design. TL wrote the study protocol and oversaw data collection. AB, TL, and LE performed statistical analyses and summarized the results. AB wrote the first draft of the manuscript. VK, BM, KM, and J-KZ assisted with interpretation of findings and provided critical revisions of subsequent manuscript drafts. All authors significantly contributed to the manuscript and approve of this submission.BM has received research funding from LivaNova and Novartis and consulting fees from Alkermes, and he has served on the advisory board of FutraMed (unpaid). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Procedures lasting more than 60 min were associated with greater pain intensity on all tested days. The sex of the patient did not significantly affect the level of the perceived intensity of postoperative pain (p > 0.05). The highest intensity of pain occurred on day 0 after surgery, with a declining trend in the following days (p < 0.001). The highest intensity of postoperative pain was caused by gynecological procedures as well as laparotomy and arthroplasty (p < 0.001). The variability of the results indicates the need for an individual approach to each patient, both in pain assessment and treatment. Therefore, continuous improvement of the quality of health services provided in accordance with the guidelines for pain relief is necessary.Currently, pain is considered the fifth vital sign, and its effective relief is a priority in many surgical departments. The aim of this study was to determine the influence of selected factors on the intensity of postoperative pain after orthopedic and gynecological procedures. The study was conducted in a group of 200 patients undergoing orthopedic and gynecological procedures at the County Hospital in Nisko between August 2017 and January 2018. The method of estimation and document analysis was applied in the course of the study. A standardized tool was used—Polish adaptation of the Melzack Pain Questionnaire (MPQ), an individual documentation of patients and a scientific and research questionnaire developed by the authors. The tests were conducted for three consecutive days from the day of the operation. The strongest pain immediately after surgery was experienced by the patients after general endotracheal anesthesia, and the mildest after full intravenous short-term anesthesia ( Currently, pain is referred to “an unpleasant sensory and emotional experience related to actual or potential tissue damage, or similar to that related to actual or potential tissue damage”  . NumerouExperts around the world are working to improve the services related to postoperative pain management. The American Pain Society has developed recommendations according to which safe and effective treatment of postoperative pain should be based on a care plan tailored to the individual patient’s needs and the type of surgery . Other pIn this study, we aimed to assess the influence on type of anesthesia, duration and type of the surgical operation and usage of premedication on the intensity of postoperative pain after orthopedic and gynecological procedures. Therefore, we assumed the following hypotheses: the intensity of postoperative pain is the lowest in patients after regional anesthesia, while the highest is after administration of short-term intravenous anesthesia; patients after long-term treatments feel pain of a higher intensity than patients after short and low-intensity treatments; the use of premedication has no effect on the pain intensity immediately after the procedure; the strongest pain sensations occur on the day 0 after the procedure, with a decreasing tendency in the following days; women experience postoperative pain more strongly; and patients after orthopedic procedures describe higher pain intensity.The study was carried out in compliance with the ethical norms set out in the relevant version of the Declaration of Helsinki  and in conformity with Polish legal regulations. The study design was approved by the Bioethics Committee at the University of Rzeszów (2018/03/13i).The method of estimation and document analysis was applied in the course of the study. A standardized tool was used—the Polish adaptation of the Melzack Pain Questionnaire (MPQ) developed by Kazimierz Sedlak . The anaThe study was conducted from August 2017 until January 2018 in a purposefully selected group of 200 patients of PCK County Hospital in Nisko . The mean age was 49 ± 15.04 years, half of the respondents were under 51, while the remaining ones were in the 38–62 age-group. The following inclusion criteria were adopted: being an adult, understanding the questions fully and consciously, and hospitalization minimum 3 days after the surgery procedure. Patients with chronic pain, multiple diseases, with limited mental comprehension or refusing participation in this survey were excluded from the study. The characteristics of the study group are presented in Dedicated research tools were used to assess whether the intensity of postoperative pain depended on the type of surgery and the anesthesia used, the extent and duration of the operation, and the sex of the patients. The standardized Melzack Pain Questionnaire (MPQ) and the patient’s medical records were used in the study. The obtained results were collected in the scientific and research questionnaire developed by the authors. The first test with the MPQ was carried out within 24 h after the procedure, and the next ones on the following days. The Polish adaptation of the MPQ by Kazimierz Sedlak consists of 74 adjectives arranged in 20 groups, each of which contains from 2 to 6 pain descriptors. There are 4 dimensions: sensory dimension of pain (groups 1–10), emotional dimension of pain (groups 11–15), subjective dimension of pain (group 16), and an additional category containing adjectives assessing various pain characteristics groups 17–20). Pain assessment is determined by: number of selected words (LWS), pain assessment index (WOB), and current pain intensity (AIB). In LWS, a maximum of 20 points can be scored, and the greater the number of words indicated, the greater the pain intensity. WOB is determined on the basis of the values assigned to individual adjectives in the questionnaire. AIB is a five-point scale (from 0—no pain to 5—unbearable pain) with which the patient determines pain symptoms at the time of the examination. In the additional tables, the subject indicates the symptoms associated with pain, assesses sleep, nutrition, vital activity, and the duration of pain. In a figure showing the human body outline, the location and radiation of pain is marked [–20. Pain2 concordance test and the binomial test). p values < 0.05 were considered statistically significant.The IBM SPSS Statistics 20 program was used for the statistical analysis. Differences between variables were verified using the chi-squared test of independence, Mann–Whitney test, Kruskal–Wallis test, Wilcoxon signed-rank test, and Spearman’s rho correlation coefficient. The choice of nonparametric tests was dictated by the lack of normality of the distributions of the variables (verified with the Kolmogorov–Smirnov and Shapiro–Wilk tests) or the lack of equivalence of the groups   .p <0.001)  .p > 0.05) (The sex of the patients did not significantly affect the level of the perceived intensity of postoperative pain ( > 0.05) .p < 0.001) (The type of surgery significantly influenced the perception of pain (< 0.001) . On daysThe conducted study concerned the determination of the influence of selected factors on the intensity of postoperative pain after orthopedic and gynecological procedures. The analysis included the dependence of the pain intensity on the type of procedure performed and the anesthesia used, the extent and duration of the operation, and the sex of the patients. The intensity of pain in the days following the procedure was examined.The time that elapses after the surgery affects the intensity of postoperative pain. The highest intensity of pain occurs on day 0 and decreases in the following days. There are reports confirming this relationship in the literature. In the research conducted by Sobieralska-Michalak K. et al., the respondents experienced the greatest pain on day 0 and the lowest on day 3 postoperatively . In a DuIn our study, the analysis of the MPQ sheet showed a dependence of pain intensity on the type of anesthesia performed. Patients experienced greater pain after general endotracheal and subarachnoid anesthesia, and lower after short-term intravenous anesthesia. Ulatowska A. et al. included 82 people hospitalized for surgical treatment in the surgical ward. They distinguished two groups: patients after cholecystostomy performed under general anesthesia and patients after removal of varicose veins of the lower limbs with subarachnoid anesthesia. They showed that the type of anesthesia used had a significant impact on the intensity of postoperative pain. Patients, both immediately after the procedure and at 4, 8, and 12 h, showed higher pain scores on the VAS after general anesthesia . Liszka It was assumed that the longer the treatment duration, the higher the pain intensity. MPQ values were the highest after procedures lasting more than 60 min, and the lowest after short-term surgery—less than 30 min. The intensity of perceived pain showed a downward trend in the days following the treatments. The results of our study are in line with the study by Mei W. et al. among over 1700 patients. They showed that longer operation time influences the intensity of postoperative pain. Among other factors, the authors also indicated younger age, obesity, the use of nitrous oxide, and location of the procedure within the musculoskeletal system and within the abdomen .The use of premedication before anesthesia had a minor effect on pain in postoperative patients. Patients who received midazolam showed slightly lower pain values after the procedure. The use of gabapentin would be more effective. It was proved by Panah Khahi M. et al. in the study of two comparative groups in which gabapentin and placebo were administered that in the first group, the pain sensation was lower immediately after the procedure than in the second . Alayed Our study indicated that the sex of the patients did not significantly affect the level of the perceived intensity of postoperative pain. However, there is no consensus in the literature regarding this statement. Mei W. et al. reported that female sex belongs to the group of independent risk factors for the development of postoperative pain shortly after a procedure . KołodziThe type of the surgery performed significantly influenced the perception of pain. On days 0 and 1, the patients reported the highest intensity of pain after gynecological procedures with laparotomy, while on day 2 after arthroplasty this had diminished. On all three days, the subjects experienced the least pain after vaginal gynecological surgeries. In the scientific literature on the treatment of postoperative pain, it is emphasized that thoracic surgeries and abdominal surgeries are the most painful, while surgeries on integuments and limbs are usually associated with much less pain. The location and extent of the procedure, the degree of tissue damage, the direction of the skin incision, and the use of specific analgesia techniques in the perioperative period significantly affect the degree of pain perception in patients . A prospThis study has several limitations that could have influenced the results. First, it was a single-center study. Another limitation concerns the study sample, limited to one population—patients treated surgically in the gynecological and orthopedic wards. It would be worth extending the research to other surgical departments such as general surgery, vascular surgery, or cardiosurgery. Moreover, the small number of participants in the study may be an additional factor limiting the critical interpretation of the obtained results; therefore further studies on larger groups of patients are needed.The factors that can influence the perception of postoperative pain are extensive: long-lasting procedures with a significant degree of tissue traumatization, and the use of general endotracheal and subarachnoid anesthesia. Patients report the strongest pain on the day of the procedure, with a decreasing tendency in the following days. The highest intensity of postoperative pain was caused by gynecological procedures as well as laparotomy and arthroplasty. The use of premedication and being a woman or a man do not significantly affect the perception of pain. The variability of the results indicates the need for an individual approach to each patient, both in pain assessment and treatment. Having considered the above, further studies would allow for a thorough analysis of the presented variables.


Methodology: This study protocol was registered with ReBec-WHO (U1111-1182-2800). From a pool of 112 patients evaluated for eligibility ), with a single asymptomatic molar (maxillary or mandibular) indicated for root canal treatment, diagnosed with asymptomatic irreversible pulpitis (including chronic hyperplastic pulpitis), 75 were randomly allocated in similar proportions to receive the intervention  in either the PTN or R group. The allocated procedures were performed using standardized protocols. Participants (blinded to the instrumentation technique) rated their pain intensity at 6, 12 and 24 h and from day 2 to day 7 following the root canal instrumentation appointment using a VAS and an NRS; the ibuprofen tablets taken and the presence of tenderness on biting were recorded. The instrumentation time was registered. Univariate and multivariate statistics measured the effect of independent variables on the outcomes. Results: From the 75 patients allocated, 8 patients (4 from each group) were lost; in total, 33 patients were analyzed in the PTN group and 34 in the R group. The frequencies of postoperative pain (p > 0.05) and tenderness on biting (p > 0.05) were similar between groups. The medication intake (mean of 1.31 tablets) and the time of instrumentation (approximately 11 min) were similar between groups. Conclusion: ProTaper Next and Reciproc® caused a slight risk of tenderness on biting and contributed to similar self-reported postoperative pain (low intensity) up to 7 days following root canal shaping.Aim: The development of postoperative pain following root canal instrumentation may impair patient’s comfort and undermine their trust in the dentist. This study assessed the effect of root canal instrumentation techniques (rotary (PTN; ProTaper Next Postoperative pain is an undesirable symptom that dental patients may experience after root canal instrumentation, and it can occur as high as 58% of the times ,2,3,4. IMany factors influence the development of postoperative pain following root canal instrumentation, such as the presence of pre-operative pain, deficient root canal technique  , higher During the instrumentation phase, the extrusion of debris and/or microorganisms beyond the tooth apical foramen  and the ® system, because of its offset design and its “wave” movement, would improve debris removal and flexibility in the working part of the file, effortlessly reaching the apical third [®) due to being a single-file technique [To minimize postoperative complications, an instrumentation technique should avoid injuries to the perirradicular tissues and smoothly reach the apical third reducing the debris extrusion. The literature on postoperative pain has showed that both rotary or reciprocating instrumentation kinematics were able to produce positive or negative outcomes. For instance, the rotary technique was associated with reduced debris extrusion in vitro  and was al third ,15. Contal third ,17,18, mal third  and reduechnique ,20. In aechnique .® and Reciproc®) on the postoperative pain intensity in patients’ asymptomatic molars (primary outcome) and tenderness on biting (secondary outcome) considering the following variables: patients’ gender, oral hygiene (good < moderate < poor) and tooth location (mandibular/maxillary), as well as the intake of analgesics during the follow up period and time of root canal instrumentation.Recognizing these divergent findings, the reciprocating technique could be more convenient for the patient, having a reduced dental-chair time and, consequently, acting in favor of patient’s comfort. This randomized clinical trial aimed to assess the effect of root canal instrumentation techniques (ProTaper Nextwww.who.int/ictrp/network/rebec/en/ (accessed on 26 December 2016) (ReBec-WHO: U1111-1182-2800). Study reporting was grounded on the Consolidated Standards of Reporting Trials  guidelines [www.wma.net (accessed on 26 December 2016)).The protocol of this parallel-group, single blind, randomized controlled clinical trial and the informed consent form were approved by the Research Ethics Committee of the university where the study was created (#1.423.099/2015). The study protocol was registered on idelines , and it idelines . PatientTM  online calculator was utilized, considering a confidence level of 95%, a power of 80%, mean outcomes in the control (PTN) and experimental (R) groups of 0.59 and 2.18, respectively, and a standard deviation of outcome of 2.3 [Sample calculation was performed to compare postoperative-pain means as a superiority trial and to verify the null hypothesis of no difference between groups. The Sealedenvelopee of 2.3 . A minimPatients were selected from a pool of 112 patients, with a noncontributory medical history, who presented at the dental clinic for examination during the study period. Eligible patients included were systemically healthy adults (≤18 years old), with one single asymptomatic molar (maxillary or mandibular) indicated for root canal treatment, pulp/periapical diagnosed with asymptomatic irreversible pulpitis (including chronic hyperplastic pulpitis) and normal apical tissues. Diagnosis was based on chief complain, visual inspection of the tooth, radiographic exam, periodontal examination  and pulp sensibility test with cold spray. The exclusion criteria were pregnancy, systemic disease with contraindication for root canal treatment, having taken an analgesic or anti-inflammatory agent prior to treatment, preoperative pain of any origin, internal and external resorption, periodontal disease, teeth undergoing orthodontic treatment, teeth with anatomic abnormalities and/or severe root canal curvature.TM website ). Block randomization was performed in order to have a list of identical numbers of patients in the control and experimental groups. To ensure allocation concealment and to control selection bias, the assistant  hid the block size from the operator and used mixed block sizes. Once the patient entered the clinic and the operator verified the fulfillment of the inclusion criteria, the list was then checked by the assistant to verify in which group the patient would be allocated. As patients were the outcome assessors, they were blind to the assigned groups. Patient and tooth-related factors , tooth location and number of canals) were registered.Randomization was conducted using the Sealed EnvelopeRotary instrumentation group (PTN): Speed was set at 300 rpm and torque at 2 N/cm. X1 was initially used for cervical preparation, and X1 and X2 reached the WL, using in-and-out movements. X3 was used as a master apical file in narrow canals and X4 in large canals.Reciprocating instrumentation group (R): R was operated in “Reciproc All” mode. R25 was used in narrow canals, and R40 was used in large canals. Three in-and-out motions were applied with stroke lengths not exceeding 3 mm in the cervical, middle and apical thirds until attaining the established WL.A single operator (P.O.S) experienced in both instrumentation techniques used in the study (5 years of practice limited to endodontics and 1 year of usage of PTN and R instruments) performed all the root canal treatments, in two appointments each. After the administration of local anesthesia , the affected tooth was isolated with a rubber dam. Following pulp chamber access and cleaning, the canals were explored with #10 and #15 K files. Working length was determined with a foramen locator (using the “0.5 mark” on display) coupled to a VDW Gold Reciproc motor . The tooth then received one of the following instrumentation techniques:For both groups, the instruments were carefully cleaned to remove debris. The operator used a sterilized gauze around the instrument shift, after 3 in-and-out movements (pecking motions). Irrigation was performed with 15 mL of 2.5% sodium hypochlorite for each canal. Final irrigation was performed with 2 mL of 17% EDTA and 2 mL of 2.5% sodium hypochlorite. Apical patency was maintained with a #15 K file beyond the working length . A persoCanals were dried using aspiration with a capillary tip and absorbent paper points. No intracanal medication was used ,14,24. TEach patient received a pain diary to record their pain at the following time points: 6, 12 and 24 h and from day 2 to day 7 following the procedure. The pain diary consisted of two scales to record pain intensity and two questions, one about analgesic intake (number of 400 mg tablets) and the other about tenderness on biting (yes-or-no question). First, patients pointed a mark in a numerical rating scale (NRS) that was a ten-point scale (10 cm) measuring 0 for no pain, 1–2 for mild pain, 3–4 for moderate pain, 5–7 for considerable pain and 8–10 for severe pain. Second, patients pointed a mark in a visual analogue scale (VAS) that was a 10 cm horizontal line with only two scores at the ends: 0, for no pain and 10 for severe pain. The distance from the patient’s mark to the 0 value was considered as a numerical value for the pain intensity. The patients were prescribed with medication following treatment; they were recommended to take ibuprofen only if they felt moderate-to-severe pain  . This rep < 0.05. Baseline demographic and clinical features , as well as time of instrumentation and number of analgesics taken, were compared between groups. A multiple intra-group analysis (PTN group and R group) of postoperative pain for the evaluated time intervals  were assessed using the Friedman test (p < 0.05). The Wilcoxon test was applied every two time intervals, with significance corrected using Bonferroni (p < 0.006). The Mann–Whitney test was used to compare the postoperative pain intensity between the groups and to compare the number of analgesic tablets ingested by the patients (p < 0.05). The effect size was calculated for standardized differences between the means of postoperative pain intensity in the groups using Cohen’s d26. The ANOVA with repeated measures investigated if the ingestion of analgesics  had an interaction with postoperative pain, considering each group (instrumentation technique).Statistical Package for Social Sciences  was used for the analysis, and statistical significance was set at p < 0.20 in the non-adjusted analysis were included in the adjusted analysis.The number of events (postoperative pain and tenderness on biting) was compared between groups (using the chi-squared test) and assessed as absolute and relative risks for the outcomes tested. Poisson regression used the postoperative pain (absent/present) at the 12 h time interval  as the dependent variable and gender, oral hygiene status (good < moderate < poor), tooth location (mandibular/maxillary) and instrumentation technique (PTN/R) as independent variables. All the associations with p = 0.536) and intake of analgesics (p = 0.988)  were included in the trial, with 38 being allocated and receiving the intervention in the R group and 37 being allocated and receiving the intervention in the PTN group. Eight patients (four from each group) were lost, because they did not show up for the second appointment , even after the researchers attempted to contact them by text message and phone call. Therefore, 34 patients were analyzed in the R group, and 33 patients were analyzed in the PTN group. The PRIRATE 2020 flow diagram shows the number of patients included in the clinical trial . Table 1The VAS showed that postoperative pain intensity was highly significant in intra-group comparisons for the evaluated time intervals. The pain peak was up to 12 h. The reduction in pain intensity for the PTN group began 6 h after the procedure, showing a tendency to decrease, but with a statistically significant reduction only between day 4 and day 5; for the R group, pain reduction began 6 h after the procedure and continued for the entire analyzed time but without statistical significance. The reduction was faster for the R group. The VAS indicated no significant differences between groups for all evaluated time intervals, but a moderate magnitude of effect was observed between groups for the periods from 24 h to day 5.The NRS also showed that the pain peak was up to 12 h. The NRS measured similar postoperative pain intensity values when compared to the VAS scale for the PTN group. Contrastingly, the NRS showed a statistically significant reduction in pain intensity between day 3 and day 4 for the R group. The NRS indicated no statistically significant differences between groups for all evaluated time intervals, but a moderate magnitude of effect was observed between groups for the periods from 24 h to day 4. p = 0.988). The overall mean of the analgesics taken by the patients was 1.31 (±2.82) tablets. A total of 16 patients, out of 20 who needed analgesics, took the medication only up to day 2 after the dental procedure. The intake of analgesics by the patients at 6 h (p = 0.112), 12 h (p = 0.648) and at 24 h (p = 0.785) had no influence on their postoperative pain, regardless of the root canal instrumentation technique.There were no significant differences in the means of the analgesics taken between groups (The frequencies of postoperative pain (primary outcome) and tenderness on biting (secondary outcome) were similar between groups. The relative risk for both outcomes showed that one instrumentation technique was not worse than the other in influencing postoperative pain intensity .A patient’s moderate oral hygiene was found to be a factor of protection against postoperative pain in both the univariate  and multivariate  models. The tooth location did not explain the primary outcome in the multivariate model .® (PTN) or Reciproc® (R) endodontic instruments caused the same postoperative pain intensity in patients, up to one week following root canal instrumentation. Since there were no statistical differences between the PTN and R instruments , this trial found that both systems may be clinically used with the same results in relation to postoperative pain to prepare patients’ root canals of molars. Molars have been previously associated with greater susceptibility to postoperative pain amongst all tooth types, because of their complex anatomy that renders debridement more difficult, increasing the risk of postoperative complications [This randomized clinical trial showed that the ProTaper Nextications . The generalizability of the study results has to be exercised with caution, because this trial investigated postoperative pain only after root canal instrumentation, which was performed in the first appointment, and not after root canal obturation. Therefore, the applicability of these findings is meaningful in regard to maintaining patients without pain (they were not in pain before seeing the dentist), ensuring their well-being and helping to build a trustworthy patient–dentist relationship, which is important for future appointments.The patients in this study experienced low pain intensity, around 1 or 2 points in both the visual analog and numerical scales. Overall, the peak of pain was up to 12 h after the procedure, and it reduced as the time passed for the patients of both groups. One important finding was that postoperative pain reduced in intensity faster for patients from the reciprocating (R) group. The reduction was noticed around the third day after root canal instrumentation (significant time point for time reduction measured by the NRS), while for patients from the rotary (PTN) group, the significant reduction in pain was observed on the fourth and fifth days after the procedure .The time of instrumentation was measured to monitor if PTN group treatment took longer since it is based on a multifile system, while R group treatment is based on a single-file system. Laboratory studies have demonstrated that all canal preparation techniques are associated with dentin debris extrusion from the root canal system ,27,28. BThis result differs from a previous clinical trial that showed more intensity and duration of postoperative pain in patients who received root canal treatment with reciprocating files compared with those who were treated with rotary files . Many arHaving knowledge of the number of medication tablets used by the patient after root canal instrumentation reinforces the dentist’s awareness of the presence and intensity of postoperative pain. Although no statistical differences were found in the means of analgesics taken between patients from the PTN and R groups , a numerical difference was found in the absolute number of analgesics taken—patients from the PTN groups took 38 analgesics in total, while patients from the R group took 32 in total. On average, 16 patients  took 1.31 tablets of Ibuprofen (400 mg) in the first 2 days following root canal instrumentation. Other clinical trials have also used Ibuprofen as the first choice to treat postoperative pain and reported that the first 48–72 h after the procedure were the most critical for the patients . Other aThis study is novel because it compared PTN and R and only included patients without pre-operative pain, since having pain ahead of the procedure is a predictor of the development of postoperative pain ,8,30,31..The standardization of the study protocols aimed to minimize or even eliminate intra-operative variables in the outcomes. As this trial had a single clinician operator, many steps of the root canal treatment that could influence the postoperative pain were controlled well, such as impact and velocity of pecking motions, style of performance of apical patency and pressure on irrigation, i.e., factors that are peculiar to each operator. Another strength of this study was the use of two types of instruments (the VAS and the NRS) to measure pain. It is believed that postoperative pain intensity can be more precisely measured when more than one scale is used—since comparing the relationships between each intensity scale and a derived composite represents the “best possible” assessment of a self-reported construct ,34. DespAnother positive point to be highlighted in this study is the use of a biting latex device to assess tenderness on biting. This study was pioneer in using this type of device and found high acceptance by the patients, since they easily comprehended the difference between tenderness on biting (manifested as a provoked sensation) and postoperative pain. The use of a latex device to reproduce symptoms of tenderness was our choice because it is more comfortable for the patient, and it presents a higher level of sensitivity than wood sticks or cotton rolls. The results showed that there was no increased risk of tenderness on biting for one of the instrumentation techniques over the other. For both groups, there was a (slight) possibility of tenderness (four patients in the PTN group and nine patients in the R group).® or Reciproc® system to instrument root canals with the expectation that patients experience low postoperative pain intensity and that they take only a few ibuprofen tablets (fewer for Reciproc®). These two instrumentation systems/techniques allow patients to bite and chew in a relatively normal way after the procedure. In addition to that, the dentist has the option to use Reciproc® with the expectation that the postoperative pain decreases faster.Implications for clinical practice include the possibility to use either the ProTaper Next® or Reciproc® instrument. Both root canal instrumentation techniques caused some risk of tenderness on biting. The patients’ intake of medication was similar regardless of the instrumentation technique. The operator needed a similar amount of time (approximately 11 min) to complete root canal instrumentation using both systems.Postoperative pain was of low intensity for patients who received root canal treatment with either the ProTaper Next


The purpose of this randomized controlled trial was to study effects of breathing reeducation in the treatment of patients with non specific chronic neck pain.A total of sixty eight eligible patients with chronic neck pain were randomly allocated to breathing reeducation (BR) group (n = 34) and routine physical therapy (RPT) group (n = 34). Clinical outcomes were neck pain measured through visual analogue score, cervical active range of motion through CROM device, strength of neck muscles through hand held dynamometer and endurance of neck muscles measured through craniocervical flexion test. The neck disability was measured through neck disability index (NDI) and pulmonary outcomes such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratio were measured through Spirolab 4. The outcomes were assessed at baseline and at 4 and at 8 weeks from baseline.There were significant improvements in the BR group compared with the RPT group (P = 0.002) for cervical flexion, extension (P = 0.029), endurance (P = 0.042), strength of neck flexors (P <0.001), neck extensors (P = 0.034). Likewise there was a significant change in NDI (P = 0.011), FEV1 (P = 0.045), FVC (P <0.001), and FEV1/FVC ratio (P <0.001) in the BR group compared with the RPT group. The cervical side flexion and rotation showed no significant difference in breathing reeducation group with p > 0.05.Breathing reeducation combined with routine physical therapy is an effective treatment in patients with non specific chronic neck pain.https://www.irct.ir/trial/46240.IRCT 20200226046623N1,  Chronic neck pain is one of the leading causes of disability imposing personal and socioeconomic burden throughout the world . The uniIt is well documented that in certain postures of cervical spine, some cervical muscles, especially the sternocleidomastoids and scaleni assume the role of accessory inspiratory muscles, and participate in rib’s elevation and thoracic stability . The oveSince the chronic neck pain can impart a negative effect on respiratory function of patients with long lasting neck pain, so a holistic treatment approach has been suggested to treat non specific chronic neck pain and its associated disorders , 15. TheDespite of plenty of literature regarding treatment of non specific chronic neck pain focusing on a multimodal treatment approach there is a lack of evidence regarding scientific testing and implementation of new treatment methods. The studies focusing on treatment of non specific chronic neck pain may have incorporated strengthening or stretching of neck muscles with postural reeducation but, no evidence was found regarding incorporation of breathing reeducation in the long term treatment protocol. According to a previous study breathing retraining may improve pain, movement patterns and neck muscle activity in patients with chronic neck pain . HoweverThere remains an immense need of well designed randomized clinical trials regarding role of breathing reeducation in non specific chronic neck pain, with cervical and pulmonary outcome measures to suggest this treatment as part of holistic treatment protocols. Thus, the aim of the present study was to explore the effects of breathing reeducation on chronic neck pain, cervical ROM, neck muscles endurance, strength and quality of life. Additionally pulmonary functions were evaluated based on the hypothesis that improving the breathing pattern will result in improved respiratory capacity which might correct the abnormal activation pattern of superficial neck muscles, improve their force exerting capacity and improve quality of life.This was a parallel group double blind (patient and assessor blind) randomized controlled trial with 1:1 allocation ratio in two groups. The trial was prospectively registered in Iranian registry of clinical trials (IRCT 20200226046623N1). The trial was conducted according to the consolidated standards of reporting trial CONSORT guidelines [1−α/2 = Standardized Level of significance = 95% = 1.96, Z1−β = Power of test = 80% = 1.28, μ1 = Mean in control group = 3.32, μ2 = Mean in physical therapy treatment group = 3.85, δ12 = standard deviation in control group = 0.38, δ22 = standard deviation in physical therapy treatment group = 0.55.The sample of 68 (34 in each group) was taken, the sample size was calculated using following formula at 80% power of study and 95% confidence level. Sample size calculation was derived from T. Duymaz study .n={ nonspecific neck pain (2) neck pain duration for more than 3 months (3) willingness to participate in the study and random allocation. The patients were excluded from the study due to the following reasons (1) upper cervical symptoms (dizziness) (2) post traumatic neck pain, pain due to disc lesion, spondylosis and neck pain of nerve root origin  (3) smokRandomization was done through sealed envelope method and patients were randomly divided in two groups, breathing group and routine physical therapy group in 1:1 ratio, by an independent administrator. All participants, clinicians, and outcome measure assessors were blinded to the randomization process. In addition, the participants and outcome measure assessors and participants were also blinded to the type of intervention.In routine physical therapy group, 34 patients , mean age 39.00 ± 4.90 years, received a treatment comprised of infrared radiation (IRR) and isometric exercises of the neck muscles. Patients were instructed to lie in prone position and IRR was applied for 10 minutes on cervical region, followed by isometric exercises for cervical muscles (flexors and extensors) in supine lying with 10 second hold and 20 repetitions. After that each patient was instructed to perform placebo breathing exercises for 15 minutes. It was unsupervised random shallow routine breathing. In breathing reeducation group there were 34 patients , mean age 39.70 ± 5.55 years, which received both routine physical therapy treatment and supervised breathing exercises. The supervision was done by an experienced physical therapist with more than ten years of experience in musculoskeletal and cardiopulmonary physical therapy. The details of the intervention are given below:The patients were instructed verbally to assume a semi-Fowler’s position  and perform diaphragmatic breathing. The instructions were given in a smooth monotonous voice to avoid any distress or anxiety to the patients. The Patients were instructed to place one hand below the anterior costal margin, on the rectus abdominis and the other hand on the belly/navel region, and inhale slowly and deeply through the nose, from functional residual capacity to total lung capacity with a three-second inspiratory hold. It was followed by an instruction to relax the shoulders, keep the upper chest quiet in order that the abdomen is raised a little. The Patients were then instructed to exhale slowly through the mouth up to five seconds. The breathing exercises were performed in 3 sets for 15 minutes, each set lasted for 3 minutes with a rest of 2 minutes between each set. In between the repetitions of the diaphragmatic breathing exercise, the patient was told to breathe normally .To avoid dizziness patients were advised to refrain from breathing from the top of the chest–try to keep the chest still and just let air in by allowing the stomach to gently rise and fall. Breathe through the nose and allow three seconds as they breathe in and five seconds as they breathe out. The total treatment time for both groups was the same. Patients of both groups received the intervention five days a week for consecutive 8 weeks.TM(USA) respectively. Functional disability was measured through neck disability index NDI (Urdu Version) [All outcomes measures were assessed by an assessor blind to treatment allocation. Pain and cervical ROM were assessed by visual analogue scale (VAS)  and CROMVersion) . CervicaVersion) , and theVersion) . The pulVersion) , 31. Theth and 8th week) and Bonferroni adjustment was used for pair wise comparison. For pair wise comparison of asymmetric variables at baseline, 4th and 8th week non parametric Wilcoxon signed rank test was used. The p value < 0.05 was considered as statistically significant for all analyzed data. All results were analyzed at 95% confidence interval.The data were analyzed using the SPSS 21.0 . The collected data were assessed fornormality using (Shapiro-Wilk test). For descriptive statistics, continuous variables were expressed as mean± SD (standard deviation), and for categorical variables frequencies and percentages were applied. For the inferential statistics, independent t-test and Mann–Whitney U test were used for between group comparison while Repeated measures ANOVA and Friedman test were applied for within group comparison at different time points , pain, NDI, endurance, strength of neck muscles and pulmonary functions. The average age, height, weight and body mass index of participants in breathing reeducation group and routine physical therapy group were 39.71±5.56 and 39.00±4.90 years, 156.35 ± 4.64 and 156.44 ± 3.66 meters, 65.15 ± 6.96 and 63.86 ± 6.09Kg, 27.01±1.67 and 26.67±1.65Kg/m^2 respectively. Whereas number of female and male participants was 14 (41.20%) and 14 (38.90%), and male participant was 20 (58.80%) and 20 (61.10%) in breathing reeducation group and routine physical therapy group respectively .The results of repeated measure ANOVA for comparison in mean scores for cervical active range of motion (AROM) at different time points (4th and at 8th weeks) revealed a statistically significant difference with  . At baseThe results of repeated measure ANOVA for evaluation of change in mean NDI score and endurance of neck flexors at different time points were statistically significant with  and  respectively . The resth and 8th week. Time*group effect was significant in breathing reeducation group according to the p values and partial eta square values where  for cervical flexion and  for cervical extension, whereas non significant for right and left sided flexion ,  and right and left sided rotation    showed that there was a statistical significant differences between breathing reeducation group and routine physical therapy group at baseline, 4, 0.231) .th and 8th week as compared to routine physical therapy group. The endurance of cervical muscles and FEV1/FVC ratio showed statistically significant differences between breathing reeducation group and routine physical therapy group , endurance of neck muscles  and FEV1/FVC ratio  which showed that the NDI score showed more improvement in breathing reeducation group at 4py group . This dipy group .th week and -4.682; 95% CI,-5.203 to-4.161; P < 0.001 at 8th week, after Bonferroni correction). The  . For Left side cervical flexion . For right side rotation of the cervical spine  and for left side cervical rotation  . For cerrection) .th week and 5.815; 95% CI, 5.170 to 6.460; P < 0.001 at 8th week, after Bonferroni correction) from baseline  from baseline   .th week P <0.001* at 8th week from the baseline. The between group comparison for strength of cervical flexors and extensors showed significant difference with P = 0.120, P = 0.436 at 4th week and P <0.001* and P = 0.034 at 8th week respectively from the baseline. The between group comparison for FVC showed significant difference with P = 0.012* at 4th week P <0.001* at 8th week from the baseline and the between group comparison for FEV1 showed significant difference with P = 0.267 at 4th week P = 0.045* at 8th week from the baseline  showed significant difference with P = 0.002* at 4baseline .th week is shown in , cervical flexor strength and neck disability index was significant in breathing reeducation group as compared to routine physical therapy group. The pulmonary functions of the patients were significantly improved in breathing reeducation group.th week providing a more vast understanding about effects of breathing reeducation. In addition to pain and ROM, endurance, strength quality of life and pulmonary functions of patients with chronic neck pain were also assessed.The results of this study are persistent to a review study about effects of breathing exercises on pain, quality of life and pulmonary functions in patients with chronic low back pain . In thisIn a previous study effectiveness of neck stabilizing exercises combined with breathing reeducation exercises was assessed in 45 patients with stroke . In the Breathing reeducation is an effective regime to improve pulmonary functions of the patients with chronic neck and back pain , 32. In The present study is the first comprehensively designed clinical trial to investigate the efficacy of breathing reeducation with routine physical therapy in chronic neck pain patients. According to the results, breathing reeducation was found effective in improving cervical outcome measures, decreasing pain and disability level in chronic neck pain patients whereas pulmonary functions were also improved.There are a few limitations of the study. Only forced expiratory technique (FET) and vital capacity (VC) were measured to assess pulmonary functions to avoid lengthy measurement procedures as patients with chronic neck pain were involved in the study. However, maximum voluntary ventilation (MVV) and chest expansion should have been measured to have a more understanding about effect of breathing reeducation on pulmonary function. Provided the lack of meticulously designed clinical trials on effect of breathing reeducation in chronic neck pain patients, multicenter pragmatic trials are required for the generalizability of the present findings in the treatment of chronic neck pain. Moreover, we recommend categorization of participants on the basis of breathing dysfunction prior to the breathing reeducation so that more understanding of the effects of breathing intervention among various categories can be understood.Breathing reeducation combined with routine physical therapy treatment improves pain, cervical flexion and extension range of motion, endurance and strength of neck flexors in patients with chronic non specific neck pain moreover; it also improves disability, FVC, FEV1 and FEV1/FVC ratio in patients with chronic neck pain. Thus, breathing reeducation may be an effective regime to improve cervical and pulmonary outcomes in chronic neck pain patients.S1 Checklist(DOC)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.


Background and objective: Our study compares the clinical outcome of chronic low back pain present for over six months treated with alpha-lipoic acid (ALA) + palmitoylethanolamide (PEA) and myrrh and periradicular infiltrations of oxygen-ozone under CT guide to periradicular steroidal infiltrations in a short (one week), medium (three months) and long-term period (six months). Methods: We enrolled 246 patients (Group A) with low back pain treated with periradicular infiltrations of oxygen-ozone under CT guide combined with 800 mg/day of ALA + 600 mg/day of PEA + 200 mg/day of myrrh orally. Group B consisted of 176 patients with low back pain treated with periradicular infiltrations of steroids. Patients were clinically monitored one week after the end of treatment, at three months, and at six months using a modified version of McNab’s method. Results: In Group A, the one-week clinical follow-up registered a complete remission of painful symptoms in 206 patients (83.7%), and this manifestation remained optimal in 191 patients at the three-month follow-up (77.6%) and in 178 at six months (72.3%). While the results were satisfactory in 28 patients (10.9%) at one week, 32 (13%) in the medium term, and 41 (16.6%) in the long term, non-significant results were found in 12 patients in the control at one week (4.6%), in 23 at three months (9.3%) and in 27 at six months (10.9%). In Group B, at the short-term follow-up we obtained an excellent clinical result in 103 patients (80.5%), while at three months 85 patients reported the persistence of clinical benefit (66.4%) and at six months, 72 (56.2%) reported the same result. The result was rated satisfactory in 11 (8.5%) and poor in 4 (3%). At the three-month follow-up, 23 (18%) reported a satisfactory result, and 20 (15.6%) had a poor result. At six months, 24 (18.8%) reported the persistence of a satisfactory result while for 32 the result was poor (25%). Conclusion: The results highlight how the treatment associated with ozone therapy and oral administration of alpha-lipoic acid + palmitoylethanolamide and myrrh can be considered a valid alternative to common therapeutic approaches in the treatment of chronic low back pain. In particular, over 70% of people in developed countries develop low back pain at a certain point in their life. This condition usually improves within two weeks, however, about 10% remain off work and about 20% experience pain after one year. Between 15% and 45% of adults experience low back pain each year, and 5% of people refer to hospital care lamenting a new acute episode ,4,5. Amo-O3) gas ,7,8 and -O3) gas ,12,13,14-O3) gas ,17,18,19When injected, the highly oxidizing oxygen-ozone mixture causes a controlled “micro-oxidation” that produces a modulation of the cellular antioxidant system and the inflammation system. This mixture provides many benefits, such as good tissue diffusion, and anti-inflammatory, analgesic, and anti-edema properties ,21.It has been demonstrated that the mixture of oxygen and ozone gas reacts with the amino acids and carbohydrates that make up the nucleus pulposus of the intervertebral disc, allowing the volume reduction of the disc itself. In the case of compression of the nerve roots following a discopathy, the oxygen-ozone mixture can determine a resolution to the clinical situation. In particular, oxygen-ozone therapy produces various beneficial effects: it reduces the inflammatory process and related symptoms such as pain, promotes the elimination of non-vital tissue in the intervertebral disc thus decreasing its volume and compression of the spinal nerve root, and promotes the elimination of harmful substances and toxins thanks to the stimulating action on the microcirculation ,22,23.Recent reviews—such as De Sire et al. , Sconza The possibility to orally combine alpha-lipoic acid (ALA) + palmitoylethanolamide (PEA) and myrrh with guided oxygen-ozone CT infiltration has been documented to be effective in further improving the clinical outcome. In a recent study, this association has been assessed and the authors concluded that it “can be considered an excellent therapeutic solution, improving the good final clinical result with better control of symptoms, particularly in the first phase of the disease” . HoweverIn light of these considerations, we, therefore, decided to further evaluate the therapeutic results in a group of 246 patients treated with CT-guided infiltrations of oxygen-ozone associated with alpha-lipoic acid (ALA) + palmitoylethanolamide (PEA) and myrrh. What led us to associate the therapies in this study was the need to investigate in more depth the enhancement that they bring to the analgesic and anti-inflammatory actions of oxygen-ozone therapy alone, together with the greater maintenance of its clinical results over time, as suggested by the literature .This association was thought of in light of the known analgesic action of ALA, which is a natural sulfur compound produced in small concentrations by all cells. ALA is, in fact, a key compound in some mitochondrial enzyme complexes (pyruvate dehydrogenase and ketoglutarate dehydrogenase), which play a central role in oxidative metabolism, and it can reduce oxidative stress by preventing oxygen-free radical damage ,30,31,32® myrrh is a dry extract of Commiphora myrrh gummy resins with a high content of bioactive furanodienes. This extract—obtained through a licensing process—allows to preserve all the properties of the original raw material.Myrrh extract blocks proteins involved in the inflammatory process such as Cox and inhibits the formation of NO, ROS, TNF-α, PGE2, NF-kB, and MAPK. Clinical studies indicate that myrrh extract is also able to induce significant improvements in osteoarthritis ,38,39,40Palmitoylethanolamide (PEA) is a natural compound rich in fatty acids which, in the body, acts as a biological modulator, favoring the physiological response of the tissues ,48,49,50It has been widely reported in the literature that oxygen-ozone is more effective than therapy through sole steroid administration . HoweverIn this study, our aim was to evaluate the efficacy of these two therapeutic approaches and to analyze and compare their effect over time, in short (one week), medium (3 months), and long (6 months) terms.From March 2019 to March 2022, we enrolled 246 patients (Group A)  with chronic low back pain treated with periradicular infiltrations of oxygen-ozone under CT guide combined with 800 mg/day of ALA + 600 mg/day of PEA + 200 mg/day of myrrh orally, after providing informed consent. Patients took 2 tablets/day for 30 days.In our sample, we included exclusively patients that had undergone a computed tomography (CT) or magnetic resonance (MR) scan. Patients manifested chronic low back pain and sciatica, which was unilateral or irradiating along the innervation territories of L3 (8 patients), L4 (71 patients), L5 (103 patients), and S1 (64 patients).Patients with bilateral lower back and sciatic nerve pain, and those with electromyographic features of neurogenic injury and/or denervation, were excluded and advised to seek neurosurgical treatment.Duration of symptoms varied from six to 20 months. We also enrolled 176 patients (Group B)  with low back pain, treating them with periradicular infiltrations of steroids. In this group, patients manifested chronic low back pain and sciatica, which was unilateral or irradiating along the innervation territories of L3 (6 patients), L4 (59 patients), L5 (63 patients), and S1 (48 patients), and also—in this group of patients—painful symptoms were present for 6 to 20 months.The injection site was disinfected, and local anesthesia was applied using an ethyl chloride spray in all patients. Infiltrations were completed by specialist neuroradiologists. The puncture site was identified by a CT scan and marked on the patient’s skin.The distance from this point to the foramen was subsequently measured.2-O3 and steroids.A 22 G Terumo needle  was positioned 2–3 mm from the foraminal region, close to the ganglion of the affected nerve root. A CT scan was then repeated to check the correct needle placement. This procedure was adopted for infiltrations of both O® was completed without contrast medium, paying special attention to the speed of infiltration. The procedure was completed slowly (over 1–2 min), to avoid the reflux of steroids along the needle trajectory. Patients with facet joint syndrome received injections into the surrounding joint capsule.Infiltration of 2 cc (80 mg) Depomedrol2-O3 was infiltrated by injecting 3 cc of the gas mixture at 25 µg/mL close to the neural foramen, then retracting the needle a few millimeters and injecting another 5 cc of the mixture to involve the facet joint region. CT scans were then used to check the correct distribution of the gas mixture in the foramen and facet joint. All treatments were carried out using equipment with photometric detection of the ozone concentration in the gas mixture , with constant pressure during the ozone intake operation. Total non-toxicity has been guaranteed, since the titanium, teflon, glass, and silicon necessary for therapeutic practice, which are inert to ozone  (The Olass 2A) A,B.(a)excellent: resolution of pain, and return to normal activity carried out prior to pain onset;(b)good or satisfactory: more than 50% reduction of pain;(c)mediocre or poor: partial reduction of pain below 70%.Additionally, clinical outcome (see tables) was assessed in all patients by short (one week), medium (three months), and long-term (six months) follow-up using a modified version of McNab’s method:2-O3-ALA and the steroid groups, we used an ordinal logistic regression model . This model considered the outcome  as the response variable and treatment , occasion , and a treatment X occasion  interaction as predictors. The model employed cluster confidence intervals to take into account repeated measures. Using this model, the difference in the proportion of patients with a poor, good and excellent outcome between O2-O3-ALA and steroid groups at the different occasions was calculated using a within-time between-group contrast with Bonferroni correction for nine groups (1 difference X 3 outcome levels X 3 occasions). Statistical analysis was performed using Stata 17.0 .To quantify the time-related change in the proportion of subjects with a poor, good and excellent outcome between the O2-O3-ALA and steroid groups.2-O3-ALA minus steroid) difference in the proportion of patients with poor, good, and excellent outcomes during the study.In Group A, the short-term clinical follow-up (one week) produced an excellent result in 206 patients (83.7%) with complete remission of painful symptoms, which remained optimal in 191 patients at the three-month follow-up (77.6%) and in 178 to 6 months (72.3%). While the results were satisfactory in 28 patients (10.9%) at one week, 32 (13%) in the medium term, and 41 (16.6%) in the long term, non-significant results were found in 12 patients in the control at one week (4.6%), in 23 at three months (9.3%) and in 27 at six months (10.9%).In Group B, at the short-term follow-up, we obtained an excellent clinical result in 103 patients (80.5%), while at 3 months 85 patients reported the persistence of clinical benefit (66.4%) and at six months 72  reported the same result. The result was rated satisfactory in 11 (8.5%) and poor in 4 (3%). At the 3-month follow-up, 23 (18%) reported a satisfactory result and 20 (15.6%) a poor result. At 6 months, 24 (18.8) reported the persistence of a satisfactory result while for 32 the result was poor (25%).® and 83.7% of patients treated with the O2-O3 mixture associated with ALA + PEA+ Myrrh). Thus, a good result was recorded regardless of the administered treatment, with effects that did not reach statistical significance , 77.6% of the patients in Group A and 66.4% of the patients in Group B remained pain-free.® deemed the clinical outcome to be excellent.At long-term follow-up (6 months), 72.3% of Group A treated with ozone and ALA + PEA + Myrrh and 56.2% of group B treated with DepomedrolTherefore, the ozone treatment associated with ALA + PEA + Myrrh was decidedly preferred in the medium and long term as a therapeutic result compared to steroid infiltrations.2-O3-ALA as compared to steroids was associated with a higher number of excellent results at 60 days  corresponding to −10% of poor cases (p = 0.0036) and −7% of good cases, (p = 0.0079).In this observational study, we found that treatment with OThe short-term outcome in our series was similar in both groups of patients, regardless of the type of treatment administered. The basis of this pain relief, produced by both steroid and ozone infiltration, appears to reflect the origin of nerve root pain. Zennaro and others claim that low back pain and sciatica have a neuritic origin. In fact, episodes of back pain and sciatica are linked to factors not strictly connected to the mechanical compression of the nerve root, but caused by an aspecific inflammatory reaction to the auto-antigens of the mucopolysaccharide matrix located on the disc surface, and exposure to contact with the immune system by migration of the disc nucleus beyond the natural barrier of the annulus fibrosus . The infThe rationale for anti-inflammatory treatment by periganglionic steroid infiltration is based on an attempt to relieve the periganglionic inflammation, by ensuring recovery of the normal ganglioneural myelin sheath, and hence nerve function at the disease site ,12,13,14This was especially evident in the short-term follow-up, roughly 80% of patients reported a clear-cut improvement in symptoms, thereby demonstrating that both treatments rapidly relieve pain.Our medium and long-term results, on the other hand, strongly favor the treatment with guided CT infiltration with oxygen-ozone associated with the administration of ALA + PEA + myrrh to the infiltration of periganglionary steroid A,B.Periganglionic steroid treatment using CT-guided paraspinal infiltration was effective in relieving root pain caused by spondylosis or herniated disc but was short-lived.In fact, in the medium and long-term controls, the success rate with steroids and the percentage of excellent results drops significantly. In addition to this, we want to underline how steroid treatment can sometimes be burdened by complications such as arachnoiditis, meningitis, paraparesis, paraplegia, sensory disturbances, intestinal/bladder dysfunctions, headaches, and epilepsy. Although these important side effects were not found in our series, a certain percentage of the drug is still metabolized.Periganglionic steroid treatment by CT-guided paraspinal infiltration is an effective tool for relieving chronic root pain but appears to be short-lived ,12,13,14To date, there is no biochemical evidence of short or long-term side effects related to ozone administration and oxygen-ozone treatment has proven highly effective in relieving chronic low back pain and sciatica. Even more effective treatment is associated with the oral administration of ALA + PEA + myrrh.Therefore, administration of the gas mixture associated with ALA + PEA + myrrh can be suggested as a first-choice treatment, to replace epidural steroid infiltration and avoid surgery.Our findings confirm the results of Bonetti et al.  regardinThis study is not without limitations. The action of the biochemical factors at the basis of the outcome of these therapies may also be studied in more detail, in the future. This need is in line with what was discussed by De Sire et al.  in theirIt could be useful to repeat this research design by adding a comparison group without 800 mg/day of ALA + 600 mg/day of PEA + 200 mg/day of myrrh orally.