Acute post-operative pain can remain untreated if patients cannot express themselves. The perfusion index (PI) may decrease when pain activates sympathetic tone and may increase after analgesics are administered. We evaluated if the perfusion index is a feasible indicator for objectively assessing pain relief in the postanesthesia care unit (PACU) and calculated the changes in PI measurements at the time of discharge from the PACU relative to baseline PI measurements to examine if the PI is a useful criterion for discharging patients from the postanesthesia care unit. This retrospective observational study enrolled female patients who were admitted for gynecological or general surgery. The patients received general anesthesia and were admitted to the postanesthesia care unit. The PI, visual analogue scale (VAS) score, heart rate, and blood pressure were recorded before and after administration of intravenous morphine. Changes in these parameters before and after analgesics were administered and the difference of these parameters between age and BMI subgroups were compared. The correlation between the PI and VAS score, ΔPI and ΔVAS, and %ΔPI and %ΔVAS were also evaluated. The percentage change in ΔPI (P9-T0/T0) of the patients at the time of discharge from the postanesthesia care unit relative to baseline PI measurements was calculated. Eighty patients were enrolled, and there were 123 instances during which analgesia was required. Heart rate, PI, and VAS score were significantly different before and after analgesics were administered (p < 0.0001). The difference of parameters between age and BMI subgroups were not significant. The correlation between the PI and VAS score, ΔPI and ΔVAS, and the percentage change in ΔPI and ΔVAS showed weak correlations in age, BMI subgroups, and all measurements. The baseline PI and the PI when arriving at and when being discharged from the postanesthesia care unit were significantly different (p < 0.01). The mean percentage change in Δ PI at the time of discharge from the PACU was 66.2%, and the 99% confidence interval was 12.2%~120.3%. The perfusion index was increased, and the VAS score was decreased significantly after analgesics were administered, but the correlation was weak in each subgroup. The VAS score is a subjective and psychometric parameter. The PI increased when partial pain relief was achieved after morphine was administered but did not reflect pain intensity or changes in the VAS score regardless of age or BMI. A percentage change in ΔPI at the time of discharge from the PACU relative to baseline PI measurements of greater than 12% can be used as a supplemental objective discharge criterion for pain assessment in the postanesthesia care unit. Pain is a subjective sensation that can negatively impact psychological and physiological wellbeing. It can stimulate the sympathetic nerve system and release stress hormones leading to increased oxygen consumption and even resulting in myocardial ischemia in serious cases . ReducinCaregivers prescribe analgesics based on the extent of surgery and their experiences in the postanesthesia care unit (PACU). They also use the visual analogue scale (VAS) score or numeric rating scale (NRS) to subjectively estimate pain severity according to patients’ facial expressions and self-reported pain scores. Then, they select the appropriate analgesic and evaluate the response to treatment. However, there are still cases of pain that remain unresolved or undertreated because the patients were unable to express themselves adequately, such as in patients with mental retardation or dementia. Several studies regarding objective pain assessment tools, such as the surgical stress index during anesthesia  and the The perfusion index (PI), which is the ratio between the variable pulsatile (DC) and nonpulsatile (AC) signals, is an indirect and noninvasive measurement of peripheral perfusion . It is cThe protocol used in this study was approved by the Institutional Ethics Review Board of National Taiwan University Hospital (Registry Number: 201604074RINB), and informed consent was waived based on its retrospective design. This study was carried out according to the International Conference on Harmonisation (ICH)/WHO Good Clinical Practice (GCP) guidelines and conformed to the principles outlined in the Declaration of Helsinki.This was an observational, retrospective, and single-center study. We reviewed medical records and enrolled female patients aged from 20 to 80 years old with an ASA class of I~III who were scheduled for gynecologic or general surgery and were admitted to the postanesthesia unit at National Taiwan University Hospital between November 2015 and May 2016. The exclusion criteria included patients who had unstable vital signs, those who were admitted as emergency cases, those who were intubated, those who were medicated with sedative or vasoactive agents, those who had been diagnosed with peripheral occlusive artery disease, and those who were admitted to the intensive care unit. The patients were monitored with automated noninvasive blood pressure on one arm, a 3-lead electrocardiogram, and a Masimo Radical 7 pulse oximeter probe  on the contralateral index finger for continuous monitoring until discharge from the postanesthesia care unit. The room temperature was maintained at 22°C, and general anesthesia was induced with fentanyl at 1~2 μg/kg, propofol at 1.5~2 mg/kg, and cisatracurium at 0.2 mg/kg. After tracheal intubation, inhalational sevoflurane or desflurane was maintained at a concentration of 1 to 1.3 MAC and adjusted according to the patient’s vital signs. After surgery was finished, patients were administered reversal agents (2.5 mg of neostigmine and 0.4 mg of glycopyrrolate 0.4 mg) when spontaneously breathing was regained, and then the patients were sent to the postanesthesia care unit for observation. According to chart record, baseline data (T0) including perfusion index, temperature, heart rate, mean blood pressure, and SpO2 were recorded 5 minutes after entering the operating room. Postanesthetic data (P0) were recorded when the patients were admitted to the PACU after surgery. The perfusion index and visual analogue scale (VAS) score were recorded when the patients regained consciousness and asked for analgesics for the first time (P1), the second time (P2), and the third time (P3). The PI and VAS were recorded as P10, P20, and P30, 5 minutes after 3 mg of morphine was administered intravenously. Before discharge from the postanesthesia care unit, the PI and VAS were recorded at time point P9. The primary hypothesis of our study was that perfusion index is correlated with VAS, and the secondary hypothesis was that the percentage change of the perfusion index would be useful as a discharge criterion for assessing the wellbeing of the patients.t-test to separately compare the differences between repeated measurements of non-parametric and normally distributed data. The Friedman test was also used to compare the PI measured at different time points. Patients were divided into age subgroups and BMI subgroups and the difference of parameters before and after analgesic administration between these subgroups were compared by Kruskal–Wallis test. Correlation between the PI and the VAS was tested by Persons’ correlation coefficient in age, BMI subgroups, and all measurements. To reduce the bias of individual variation in perfusion index, we also evaluate the correlation between the ΔPI  and ΔVAS , and the percentage change in ΔPI  and the percentage change in ΔVAS . The PI measurements at the time when the patients met the discharge criteria were compared with the baseline PI measurements. The percentage change in Δ PI (P9-P0/P0) at the time of discharge from the postanesthesia care unit was calculated, and 99% confidence intervals were constructed to evaluate the use of this measure as a discharge criterion, along with VAS scores < 3. All the tests were 2-tailed, and p < 0.01 was considered statistically significant.We used GraphPad Prism 6 to perform the statistical analysis. Continuous data are shown as the mean ± SD, and categorical data are shown as percentages. The Shapiro-Wilk test was used to test the normality of the distribution. We used the Wilcoxon signed-rank test or the paired One hundred three patients were screened, and 80 patients met the inclusion criteria. The demographic data are shown in 2). All the patients had a VAS score < 3 with regard to their wellbeing when they were discharged from the postanesthesia care unit. The mean percentage change in ΔPI (P9-P0/P0) at the time of discharge from the postanesthesia care unit was 66.2%, and the 99% confidence interval was 12.2% ~ 120.3%.In total, there were 123 requests for analgesic medication. The PI before analgesic administration  and the PI after analgesic administration  were significantly different (p < 0.0001). The VAS score and heart rate before and after analgesic administration also significantly changed (p < 0.0001) . The PI The perfusion index (PI) is derived from plethysmography and is a non-invasive and convenient tool for evaluating peripheral perfusion. It can be used in routine anesthetic practice and can help anesthetists to make decisions based on its characteristics. Several studies were carried out in recent years because the perfusion index was thought to have become more stable and reliable . It has In our study, the PI at the time of arrival to the postanesthesia care unit was lower than the baseline PI as a result of acute post-operative pain. There was a significant change in heart rate, PI, and VAS before and after the administration of intravenous morphine. Pain can stimulate a sympathetic reaction that increases heart rate and results in peripheral vasoconstriction, leading to a decreased PI. Morphine is an effective and safe analgesic medication for managing acute post-operative pain that can be given incrementally . When ac2) This can be explained because the VAS score is subjective and is based on psychometric properties. Patients may still report higher VAS scores when they suffer from poor emotional and psychological wellbeing even if analgesics are administered. The PI increased due to partial pain relief when analgesics were administered but did not reflect the VAS scores that the patients subjectively reported. This irrelevant phenomenon existed regardless of age and BMI. The only significant correlation between PI and VAS before and after analgesic was due to rather few measurements in morbid obesity group.Like in a previous study, the correlation between the perfusion index and the VAS score was not established in our study. The ΔPI and ΔVAS were not significantly correlated, and the percentage changes in ΔPI and ΔVAS were also not significantly different. There was still no significant correlation in age and BMI subgroups with exception of PI and VAS before and after analgesic administration in obesity group Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.


Background. Dexamethasone is sometimes used as a coanalgesic because of its anti-inflammatory properties. Objective. To evaluate opioid use, postoperative pain intensity, and side effects after a single dose of dexamethasone in patients undergoing arthroscopic knee surgery. Methods. In this randomized controlled study patients were randomized to receive either 10 mg of intravenous dexamethasone (DM group) or 0.9% normal saline (NS group) during the intraoperative period. Primary outcomes were pain intensity and total morphine and codeine use after surgery. Results. Seventy-eight patients were included in the study. The DM group showed statistically significant higher pain intensity at the fourth postoperative hour . No statistically significant difference in total opioid use (morphine plus codeine) was identified with 15.9 (SD 1.97) codeine tablets used in DM group and 20 (SD 2.14) in NS group (p = 0.25). Discussion. Pain intensity tended to decrease in both groups suggesting morphine as the main source of analgesia. Conclusions. Intravenous dexamethasone during the intraoperative period has no clinical impact on postoperative pain intensity during the first 48 h after arthroscopic knee surgery. This trial is registered with R000020892. For this reason, glucocorticoids can be used in the treatment of acute pain [Tissue lesions formed during surgery induce the production of multiple nociceptive mediators such as prostaglandins, which are produced via the arachidonic acid cascade. Glucocorticoids decrease the level of prostaglandin synthesis by indirectly inhibiting the activity of phospholipase A2 and cyclooxygenase II. Glucocorticoids can also modulate the inflammatory response by inhibiting the production of cytokines, including tumor necrosis factor ute pain .Two meta-analyses conclude there is a minimum but statistically significant analgesic benefit when administering a single intravenous perioperative dose of dexamethasone , 6. HoweAlthough optimal analgesia is the primary desired outcome of postoperative pain management, reducing the incidence of adverse effects is also important, particularly in outpatients. Combining treatments with different mechanisms of action allows clinicians to use lower doses of each agent, thereby limiting the adverse effects associated with each. For example, a combination of nonsteroidal anti-inflammatory drugs, opioids, and peripheral nerve blocks with local anesthetics has proven to be effective in controlling inflammation and acute pain .While dexamethasone may play a role in multimodal pain management therapy, more studies are needed before its routine use can be recommended –12. The This study had a randomized, blinded, placebo-controlled, parallel group design and was conducted at a university hospital with 190 beds. It was approved by the institutional ethics committee and all procedures were in accordance with the Declaration of Helsinki. We included 78 outpatients aged 18 years or older who were scheduled to undergo arthroscopic knee surgery by one of the surgeons. Exclusion criteria were cognitive impairment or communication difficulties, a high risk of postoperative nausea and vomiting, and contraindications to dexamethasone/diclofenac use. Patients were randomly assigned to control or treatment groups according to a computer-generated table. This randomization sequence was then given to the pharmacy coordinator (the only person to know the sequence); group assignment remained unknown to those directly involved in patient care.The pharmacy staff members present in the operating rooms were responsible for preparation of the study solutions, which were labeled for group 0 or group 1. Immediately before anesthetic induction, the syringe with the appropriate study solution was given to the anesthesiologist in charge of the patient. The assignation sequence was sealed in an envelope kept at the hospital pharmacy, and a copy was maintained at the Department of Anesthesiology office until the end of the study. The content of the syringes remained unknown to the anesthesiologist, the patients, and the anesthesia staff who collected the data.−1·min−1, and inhaled sevoflurane at a minimum alveolar concentration of 0.5–1 (1-2% of sevoflurane) and FiO2 of 0.7 was maintained. All patients received 50 mg of diclofenac intravenously immediately after intubation and 0.1 mg/kg of morphine intravenously approximately 20 min before the end of surgery.In the control group (NS group), patients received 2 mL of 0.9% normal saline intravenously at the onset of anesthetic induction. In the treatment group (DM group), patients received 2 mL of a 5 mg/mL dexamethasone phosphate solution at the onset of anesthetic induction; the two study solutions were physically indistinguishable. Patients underwent standard anesthetic protocols: 2-3 mg of midazolam was administered intravenously at the start of induction, followed by 3–5 mg/kg of thiopental sodium, 0.05–0.1 mcg of remifentanil·kgWe assessed pain intensity using a visual analog scale (VAS); adverse effects, such as nausea or vomiting, were recorded in the postanesthesia care unit at 4, 8, 12, and 24 h postoperatively. Upon discharge, each patient received an envelope containing 30 tablets of 30 mg codeine phosphate; patients were instructed to use up to 10 tablets daily (300 mg) and to record their daily intake in a booklet. Patients were then called and questioned regarding the total number of codeine tablets consumed within 48 h postoperatively.β statistical power of 80% and an expected patient withdrawal rate of 10%.To confirm an advantage of dexamethasone over placebo, assuming a 30% reduction in pain intensity from hospital admission to 48 h after surgery, we calculated that a sample size of 80 patients (40 patients per group) would be needed given a t-test was used to evaluate differences in mean values between the groups and to assess correlations regarding morphine use. A Wilcoxon rank sum test was performed to evaluate differences in patients' satisfaction with codeine analgesic treatment between the groups and to assess correlations between codeine and morphine use. Analysis of variance was used to compare repeated variables between the groups. Statistical significance was set as p < 0.05.Patients' characteristics were recorded in an Excel database. Continuous variables were described using measures of central tendency and dispersion. STATA version 10.1 was used for statistical analysis. Student's p = 0.015).A total of 152 patients were screened; 65 of these patients were withdrawn during enrollment because they did not meet inclusion criteria or declined to participate. Eighty-seven patients were included in the study , and 78 (90%) of them  completed the study . A totalp = 0.0366)  .p = 0.79). The mean morphine dose administered during the postoperative period was lower in the DM group, but again the difference was not statistically significant. No correlation was identified between the doses administered during the intraoperative and postoperative periods.As shown in p = 0.2557).In both treatment groups, the lowest consumption of codeine tablets occurred on the day of surgery; consumption increased on the first postoperative day and then decreased again on the second postoperative day. The mean number and total number of codeine tablets taken during the first 48 h postoperatively were lower in the DM group , althougp = 0.69) and the presence of adverse effects, were observed between the groups (data not shown).No correlation was observed between the number of codeine tablets taken and the morphine dose administered at the different time points evaluated. No significant differences in secondary outcomes, that is, patients' average level of satisfaction with analgesic treatment  in the first 12 h postoperatively. The lack of a significant difference in pain intensity between the groups suggests that morphine was the main source of analgesia. The finding of similar pain intensity between the groups in our study conflicts with reports showing a significant decrease in pain following steroid administration.Our study's most important findings regarding pain intensity were the low initial scores in both treatment groups that persisted throughout the study period and the lack of a significant difference in opioid analgesic use between the groups. The low pain intensity scores may have been responsible for the absence of intergroup differences; previous studies have reported mild postoperative pain intensity . It shouTherefore, this study fails to show additional benefit of adding intravenous dexamethasone. A study evaluating the endocrine and immune effects of dexamethasone in total knee replacement found it inhibited the increase in monocyte count and had an effect on cortisol concentrations regulating the extent of systemic inflammation . HoweverThe main limitation of this study was its small sample size, which diminished the statistical power and made it difficult to identify differences between the groups. However, given that no significant differences were found between the groups at baseline, the chance of making a type I error was small. The short postoperative follow-up period could be considered another limitation. However, we found no differences in pain intensity or analgesic use during the critical postoperative period when patients returned home; accordingly, we did not expect large differences in analgesic use or increases in acute pain intensity after this period. Another limitation was having surgeries done by various surgeons instead of one since we did not measure degree of trauma on each patient nor did we describe the technique used by each surgeon which could have influenced pain level. One last limitation was measuring VAS score at rest only and not again under dynamic conditions to evaluate how pain changes with ambulation.Based on our results, administering 10 mg intravenous dexamethasone during the intraoperative period does not improve analgesia on postoperative pain intensity during the first 48 h after arthroscopic knee surgery when administered in conjunction with another anti-inflammatory. Morphine and codeine use, treatment satisfaction, and the incidence of adverse effects were similar in the treatment and control groups. Further studies using higher doses and an opioid different to codeine are advised.


The purpose of this study is to highlight the evidence of signs and symptoms of craniomandibular disorders (CMD) in patients suffering from fibromyalgia.The study has been carried out from May 2011 to May 2015, recruiting a sample of fibromyalgia patients at the Department of Neurophysiopathology at the hospital Policlinico in Bari. Among the 150 examined patients, 60 of them have been diagnosed to suffer from fibromyalgia and 27 accepted to be investigated with a gnathologic examination at the Dental School at the University of Bari.24 patients (88.9%) were women and 3 (11.1%) men; from 26 to 66 years old . 14 patients (51.9%) were affected by primary fibromyalgia, the remaining 13 (48.1%) by secondary fibromyalgia, mainly associated with hypothyroidism (29.6%). VAS average score was about 8 ± 1.85. The frequency of pain was daily in 15 patients (55.6%); twice a week in 10 patients (37.03%) and a few times a month in 2 patients (7.4%). 11 patients (40.7%) attributed the onset of fibromyalgia to a specific instigating event. In addition, from the gnathologic anamnesis, 11 patients  reported a painful symptom in the head-neck region, especially in the frontal region, in the neck, in the masseter muscle and ATM. VAS average score was 3.4 ± 2.8, significantly lower than the one referring to the fibromyalgia pain. The gnathological examination found CMD signs and symptoms in 18 patients (66.7%). Concerning the prevalence of CMD, in type I fibromyalgia, myofascial pain was more frequent (5 patients), whereas in type II fibromyalgia, what was more frequent was a dislocation with reduction (3 patients).Based on clinic experience, we can affirm that some patients with CMD report pain in other regions. It is difficult to distinguish the CMD forms directly correlated to fibromyalgia from those engendered by parafunctional activities; hence the need is to resolve the fibromyalgia syndrome adopting a multidisciplinary approach. Fibromyalgia -3 is a fvs. 0.5%) with an onset peak between 45 and 60 years of age [Fibromyalgia has a prevalence of 2%, mainly in the female gender  are a series of clinical dysfunctions involving masticatory muscles, temporomandibular joint (TMJ) or both; there is a strict correlation with other muscle-articular structures of the head and neck and with the postural stance .A physical diagnosis (axis I) and an evaluation of the social and psycho-affective involvement (axis II) are classified according to the RDC/TDM (Research Diagnostic Criteria for Temporomandibular Disorders) . The phyThe signs and symptoms of CMD are widespread in adult population with a prevalence of the formers and an average value of 44% against 30% of the latter , but theThe main signs and symptoms are muscle pain in the head and neck, noise and pain in the temporomandibular joint, alteration of the mandibular mobility; further symptoms are cephalea, facial and nape pain, dental pain, tinnitus dysgeusia.CMD has a multifactorial genesis. The pain is determined by a complex interaction between mechanical, biological, cognitive and psycho-emotional factors. In addition, there are perpetuating, instigating and predisposing factors.The predisposing factors include morphostructural alterations , psycho-emotional  and pathophysiological alterations (para-functions).The instigating factors include overload, micro and macro-traumas. Perpetuating factors are to be found in the psycho-emotional dimension of the patient  .The most frequent symptom is pain ; CMD is CMD treatment can be causal or symptomatic, taking into consideration the symptoms, severity and duration of the pathology.Both fibromyalgia and persistent pain associated to some cases of CMD have long been considered as chronic muscle-skeletal pain conditions; the comorbidity of the two pathologies appears therefore evident.Even though the craniofacial region is not included by ACR criteria in the diagnosis of fibromyalgia, it is reasonable to think that diffuse pain can affect this region. The first studies concerning this matter showed that fibromyalgia patients could show symptoms associated to some types of CMD, like pain in the masticatory muscles and TMJ; furthermore, some patients with CMD complain a more diffuse pain, extending beyond the craniofacial region.One of the first studies on the correlation between fibromyalgia and CMD dates back to 1988 : this stIt has been observed that a wide percentage of subjects with localised myofascial pain in the orofacial region also report pain in other body regions, and that the 20% of patients with signs and symptoms of CMD are positive to ACR criteria for the diagnosis of fibromyalgia. For this reason, some authors inferred that fibromyalgia and myofascial pain in the masticatory muscles are different manifestations of a single syndrome picture. Based on these considerations, a study  comparedConsidering that pain is a symptom both in fibromyalgia and CMD, the present study aims to describe the involvement of masticatory muscles and temporomandibular joint in fibromyalgia patients according to the RDC/TDM, analysing a group of these patients.The study has been carried out between May 2011 and May 2015, recruiting a sample of fibromyalgia patients at the Department of Neurophysiopathology at the Policlinico hospital in Bari.Among the 150 examined patients reporting chronic pain not attributed to any pathology, 60 were diagnosed fibromyalgia and 27 accepted to undergo a gnathological examination.In agreement with the criteria of the American College of Rheumatology (ACR) , the incDiffuse pain for at least 3 months;Pain in at least 11 among the 18 tender points after digital palpation in 9 body regions.For each member of the sample, we recorded age, gender, job and we determined the type of fibromyalgia distinguishing between:Primary: there are not any laboratory tests alterations nor association with other diseases;Secondary: it emerges during the course of another disease defined “main disease” .We performed a neurological control visit and then we carried out, at Dental School at the University of Bari, a gnathological evaluation in order to verify the presence of diffuse pain in the orofacial region and signs of CMD. The gnathological evaluation was performed in agreement with the protocol defined by the European Academy of Craniomandibular Disorders. This protocol includes the compilation of a dedicated medical record, made up of an anamnestic questionnaire and an objective examination. The anamnesis consists of the patient’s personal data compilation, the assessment of their overall health status, followed by a specific investigation of the reported symptoms of CMD, such as pain in face, head and neck, presence of articular noise (click/crackling), disorders of the mandibular function . The objective examination was carried out making the patient undergo a series of examinations and orthopaedic tests with the aim to examine the mandibular dynamics (possible limitations and/or deviations/deflections) and to detect possible pain , dental abrasion facets due to parafunctions and articular noises.At the end of this diagnostic protocol, the patients were classified according to the RCD/TMD criteria  in one oGroup 1: Muscle pathologies- 1a: myofascial pain1b: myofascial pain with partial openingGroup 2: Disc dislocations- 2a: disc dislocation with reduction2b: disc dislocation without reduction, with partial opening2c: disc dislocation without reduction, without partial opening- Group 3: Arthralgia – arthritis – arthrosis3a: arthralgia3b: osteoarthritis of ATM3c: osteoarthrosis of ATMIn the follow-up checks, the neurologist asked the patient about possible change in symptoms and improvement due to the treatment. Pain was measured with VAS scale score points, and then matched with the value reported in the previous checks; after this, the palpation of tender points examination was repeated.The intensity was examined with the Visual Analogue Scale (VAS), with an arbitrary score ranging from 0 to 10, where 0 is absence of pain and 10 is the maximum pain experienced by the patient. Patients were asked to describe the maximum pain they had experienced and to indicate where they would locate the intensity of the present pain in the scale, giving it a proportional score.1, we have reported the demographic and clinical data of fibromyalgia in the examined patients.In Table We recruited 27 patients. 24 patients (88.9%) were women and 3 (11.1%) men; from 26 to 66 years of age . 14 patients (51.9%) were affected by primary fibromyalgia, the remaining 13 (48.1%) by secondary fibromyalgia, mainly associated with hypothyroidism (29.6%). VAS average score was about 8 ± 1.85; the frequency of pain was daily in 15 patients (55.6%), (37.03%) twice a week in 10 patients and (7.4%) a few times a month in 2 patients.Most patients were assessed according to their socio-economic sphere and as it is evident from the table most of them did not have a job either because they were housewives (48.1%) or because they had left their job because of the limitations due to their pathology.Starting from the anamnesis, we inferred the characteristics of pain reported by the patient: in those cases where the VAS score was low, the pain was described as a tingling sensation; higher scores corresponded with burning, piercing pain with a sensation of needle sting, stabbing or electric shock, often together with fatigue and weakening.Almost all patients reported that their pain worsened depending on changes in weather conditions or after mild physical activity , but above all in stressful conditions.2, we report the data relative to the specific gnathological anamnesis.In Table Based on these data, it emerges that 11 patients  reported a painful symptomatology in the head-neck region.The VAS was on average 3.4 ± 2.8, significantly lower than the one reported for fibromyalgia pain. 10 patients (37.03%) reported the CMD symptoms after the diagnosis of fibromyalgia, while 1 patient (3.7%) reported before.13 patients (48%) reported the presence of parafunctional habits. 8 patients (29.62%) were under treatment with occlusal plate.In the 18 patients (67%) where it was possible to detect symptoms and signs of CMD, the following sub-groups were identified:6 with disc dislocation with reduction (classified as 2a);1 with disc dislocation without reduction (2b);7 with myofascial pain (1a);3 with myofascial pain and disc dislocation with reduction (1a+2a);1 with myofascial pain and disc dislocation without reduction (1a+2b).Concerning the prevalence of CMD in two fibromyalgia subgroups, in type I fibromyalgia, we found a more frequent presence of myofascial pain (5 patients), while in type II fibromyalgia, the disc dislocation resulted as more frequent (3 patients).Despite the fact that the head-neck region is not included in the ACR criteria for the diagnosis of fibromyalgia, it is reasonable to assume that it is affected by diffuse pain involving the rest of the body.A study on 191 fibromyalgia patients found that 94% of them complained of localised pain in the temporomandibular region .A study examined the prevalence of signs and symptoms of CMD in fibromyalgia and reported that in 53% of the fibromyalgia examined patients, the presence of CMD was seen .Similarly, considering our experience, we can affirm that some CMD patients complain pain in other regions , 17.In the present study, we found that 67% of fibromyalgia patients showed signs and/or symptoms of CMD, mainly referable to the sub-groups of myofascial pain  and disc dislocation with reduction (22.3%); none of the patients resulted to belong to the third group.The explanation of the higher evidence for these two types of CMD could lie in the etiopathogenetic mechanism of fibromyalgia, which leads to the chronicization of a disorder, in most cases self-limiting in time.In fibromyalgia patients, the transmission path of pain is altered with consequent facilitation and/or failure of the inhibition of the nociception resulting in an increase in sensitivity and in the perception of pain at a central level. This affects the dynamic balance of the whole system, which passes from a state of physiological adaptation to a dysfunctional and clearly pathological one. These modifications are reflected also in the stomatognathic system causing localised pain burdening the masticatory muscles and limiting mandibular movements. The pain can be further exacerbated by concurrence with stress and depression, which often is associated with fibromyalgia although the patient, in most cases, tends to underrate craniomandibular problems perceived as of secondary importance and not associated with the main pathology. VAS average score for CMD is 3.4 ±2.8, below the 8±1.85 of patients with fibromyalgia syndrome.A study  found thA study on patients with fibromyalgia  showed tGiven the different time of onset of diffuse and localised pain in the orofacial region, it has been suggested that fibromyalgia may affect first other body segments and then reach the head-neck region.Most of our patients report the onset of head-neck region upsets later than other body parts; this leads us to assume that fibromyalgia emerges first in other regions and then becomes an instigating factor of CMD.It is therefore important to understand if facial pain emerges before or after the fibromyalgia syndrome, because it could be an associated comorbidity factor or an instigating factor of fibromyalgia, also, in the light of the fact that in patients with CMD, we can report pain outside the temporomandibular region. Many of the patients with fibromyalgia can develop inflammatory-degenerative disorders affecting the ATM and masticatory muscles, highly likely to be caused by a secondary effect of muscle pain; in the light of these observations, the study suggests that fibromyalgia can be a medium-term, long-term risk factor for CMD.A study  investigSome authors  argued tBased on the results of the study, we can affirm that fibromyalgia and diffuse pain are risk factors complicating the management of CDM and they therefore have to be taken into consideration in both the evaluation and the treatment of CMD.In our study, we found that 67% of fibromyalgia patients showed signs and/or symptoms of CMD, mainly referable to myofascial pain  and disc dislocation with reduction (22.3%). Fibromyalgia may lead to the chronicization of a disorder, in most cases self-limiting in time. The pain can be further exacerbated by concurrence with stress and depression, which often is associated with fibromyalgia although the patient, in most cases, tends to underrate craniomandibular problems perceived as of secondary importance and not associated with the main pathology.It is however difficult to distinguish the CMD forms directly correlated to fibromyalgia pathology from those due to parafunctional activities, which were present in 48% of the sample; in opposition, in patients under treatment with occlusal plate, any improvement in symptoms has not been seen. Hence, a resolution of fibromyalgia syndrome adopting a multidisciplinary approach is required.In order to obtain more reliable results, it is necessary to study a wider sample of patients and then match the obtained data with a control group.


There has been an increase in the number of Japanese patients with lumbar spinal canal stenosis (LSCS) who complain of chronic pain or motor disturbance in the lower back or extremities. These patients are often treated with anti-convulsive drugs, opioids, antidepressants, acetaminophen, or nonsteroidal anti-inflammatory drugs, all of which can cause side effects. For this reason, Japanese traditional herbal medicine (Kampo) is of interest, because it produces fewer adverse reactions. The aim of this retrospective cohort study was to analyze the effects of Kampo in patients with LSCS.n = 111, group K) and without  Kampo. Use of pregabalin and opioids decreased significantly in group K (p < 0.001). The hazard ratio for opioid discontinuation was 0.220 (p = 0.004) for group N vs. group K, while that for pregabalin and antidepressants discontinuation were 0.589 (p = 0.202) and 0.509 (p = 0.377), respectively. The mean duration of hospital visits and treatment did not differ between the groups, but the number of dropouts was significantly higher in group N (p < 0.0001). The hazard ratio for patient dropout was 4.118 (p = 0.001) for group N vs. group K.A total of 151 patients with LSCS were divided into two groups based on treatment with (Kampo led to discontinuation of opioid use for pain in patients with LSCS, and patients who were treated with Kampo were more likely to continue treatment. The symptoms of lumbar spinal canal stenosis (LSCS), such as low back pain, lower limb pain, and intermittent claudication, often develop into chronic conditions. The increasing number of LSCS patients is a social issue because of the resulting decrease in labor productivity, reduction in health expectancy, and increase in health care costs , 2. PainJapanese traditional herbal medicine (referred to as Kampo) is of interest to pain clinics because it produces fewer side effects , 6. In oWe often encounter patients with pain who cannot use adequate doses of Western medicines, e.g., opioids or anti-convulsive drugs, because of their side effects, but can obtain moderate or high levels of satisfaction from Kampo.The aims of this study were to analyze the recent use of Kampo in our outpatient pain clinic and to evaluate the effects of Kampo on outcomes with respect to its usability for pain management in outpatients. In addition, according to the hypothesis that a combination therapy using Kampo alongside Western medicine may have value, we examined the treatment progress of LSCS patients who complained of chronic low back pain, the most common condition in the outpatient department of our pain clinic in a retrospective cohort.n = 111), while those in group N were not (n = 40). Data were collected on the following patient characteristics: therapeutic regimens involving nerve block or near-infrared light therapy, rehabilitation, and drug prescriptions. We also assessed periods of hospital attendance, and outcomes that involved either an end to therapy, continuation of therapy, or dropout during the observation period. These data were compared between the two groups.The study was approved by the ethics committee of Iwate Medical University Graduate School of Medicine (No H29-56). Clinical data for patients with LSCS admitted for ambulatory care between January 2015 and December 2016 were obtained from electronic records. LSCS patients who continued to visit our hospital for over 1 month were included in this study. To exclude acute nociceptive pain, we excluded subjects whose treatment ended within 1 month. The diagnosis of LSCS was made on the basis of clinical symptoms, e.g., low back pain, numbness in a lower extremity, or intermittent claudication seen in magnetic resonance imaging (MRI) of the lumbar spine. Observation and diagnosis using MRI were performed by radiologists in our institution. Patients with LSCS who received treatment for other painful diseases were excluded. A total of 151 patients were enrolled and divided into two groups; patients in group K were prescribed Kampo  was used for statistical analysis. The Shapiro-Wilk test was used to determine whether data were normally distributed. Continuous data were expressed as median, 25th and 75th percentiles, or as mean ± standard deviation. Categorical variables were expressed as numbers or as percentages of patients. Continuous variables were compared using a Mann-Whitney The characteristics of the 151 patients in the study are shown in Table The formulas for Kampo prescriptions are shown in Table p = 0.0012). Similarly, the use of opioids discontinued more often in group K (p = 0.0002). On the other hand, the use of antidepressants slightly decreased in group K (p = 0.063). The estimated hazard ratio for discontinuation of opioids was 0.220  for group N vs. group K, while that for pregabalin and antidepressants were 0.589 , 0.509 , respectively. The number of patients who discontinued use of NSAIDs and/or acetaminophen was not different between the groups (p = 0.891).The details of the effects of Kampo on the reduction of use of other drugs are shown in Table p < 0.0001). We did not ignore these dropout patients in all of the analysis. The hazard ratio for patient dropout was 4.118  for group N vs. group K.The duration of hospital visits and treatment and the outcomes are shown in Table Japanese traditional herbal medicine (Kampo) is covered by national medical insurance and widely used for pain management , 8. Kampp = 0.004) for group N vs. group K, while that for pregabalin and antidepressants were 0.589  and 0.509 , respectively. This means that the treatment with Kampo medicine led to significant discontinuation of opioids treatment but not of pregabalin and antidepressants treatment.In this study, we assessed the effects of Kampo on the clinical course of patients with LSCS who complained of low back pain. The incidence of side effects caused by Kampo formulas was only 6.3% (7/111 patients), while 62.5% of patients treated without Kampo had side effects such as constipation, nausea, sleepiness, eruption, or edema. Therefore, the combined administration of Kampo decreased side effects compared to the use of Western-style medicines alone. The Cox proportional hazards model analysis showed that the estimated hazard ratio for discontinuing opioids was 0.220 (95% CI 0.078–0.615, The most important finding in the study was that Kampo prescriptions led to discontinuation of Western medications, especially opioids. In addition, patients who were prescribed Kampo continued to undergo treatment for longer periods.This study has some inherent limitations. First, the retrospective design, small number of patients, and large difference in numbers in the two groups raise concerns about statistical validity. Second, the patients were divided into groups based on whether their prescriptions included Kampo, but we do not know whether this classification method was adequate. Third, we did not analyze the symptoms using an Oriental medical approach, and the evidence level for use of Kampo is still relatively low. Further analysis is therefore required, in a prospective trial of Kampo, to validate the findings in this study.


Nutritional disorders have been reported to be important causal factors that can intensify or cause a painful response in individuals with chronic musculoskeletal pain.To assess the habitual intake of and the serum and erythrocyte levels of selenium and zinc in patients with chronic myofascial pain.A case-control study of 31 patients with chronic myofascial pain (group I) and 31 subjects without pain (group II). Dietary record in five days for assessing food intake were used. The serum and erythrocyte concentrations of selenium and zinc were analyzed using an atomic absorption spectrophotometry. Pain intensity was assessed using a visual analog scale.vs. 90.80 ± 23.12 μg/L; p = 0.041) and zinc . In this study, a compromised food intake of zinc was observed in the majority of the subjects in both groups. The selenium intake was considered to be safe in 80% of the subjects in both groups; however, the likelihood of inadequate intake of this mineral was twice as high in group I . In the logistic regression analysis, the erythrocyte concentration of zinc was associated with the presence of pain. In each additional 1 mg of Zn2+ per gram of hemoglobin, a reduction of 12.5% was observed in the risk of the individual having chronic myofascial pain . Physical inactivity and obesity were noted more commonly in group I compared with the control group.The group of patients with chronic myofascial pain, compared with the control group, showed a lower erythrocyte concentration of selenium (79.46 ± 19.79 μg/L In this study, patients with chronic myofascial pain showed lower intracellular stores of zinc and selenium and inadequate food intake of these nutrients. Myofascial pain syndrome (MPS) is defined as a regional pain that originates in a corresponding muscle area, and the referred pain is attributed to the presence of a “taut band” where one can locate the “myofascial trigger points” (MTrPs) 2]. Howe. Howe2].There are several mechanisms underlying the development of MTrPs and the appearance of MPS. Although there is no consensus diagnosis, the factors that may predispose individuals to the development of MTrPs are as follows: acute trauma, repeated micro trauma, lifestyle, posture, the lack of vitamins and trace elements, sleep disorders and joint problems that predispose to the development of micro traumas  or the mRelative ischemia, which is associated with muscle spasms, can cause significant damage to the affected tissues in MPS . EvidencThe influence of antioxidants on painful nociception and the reduction of damage caused by free radicals in patients with chronic musculoskeletal pain are controversial 16]17][[17][16][[[17][16]This study was approved by the Ethics and Research Committee of the School of Nutrition of the Federal University of Bahia—number 03/08. The patients who were eligible to participate in the study signed an informed consent form before the participating in the study.This exploratory and observational case-control study consisted of adults with chronic myofascial pain who were followed in a specialized pain-care unit at a university hospital in northeastern Brazil.To calculate the sample, we determined the mean values of serum concentrations and the standard deviations found for magnesium and calcium in the pilot project and the mean difference to be detected as significant based itself on original published studies on patients with chronic musculoskeletal pain. Considering a significance level of 5% and a power of 90%, we analyzed the expected sample size for each trace element.The subjects of this study were divided into two groups: group I consisted of patients who were diagnosed with chronic myofascial pain, and group II consisted of healthy subjects, who were paired by age and socio-economic status.Group I (case) consisted of individuals of both genders who were diagnosed with chronic myofascial pain that was associated with the presence of MTrPs and muscle pain scores of > 4 assessed by the pain scale and who were aged 18–60 years. Group II (control) comprised family members and companions of patients who were from the same area or district, were of similar socioeconomic conditions and had undiagnosed pain.Trichinella spiralis, cysticercosis and toxoplasmosis, Hepatitis B, C, HTLV or HIV, chronic fatigue syndrome and fibromyalgia). Individuals with electrolyte disturbances or users of diuretics were also not included in this study.Individuals were not included in this study if they were diagnosed with radiculopathy, degenerative or inflammatory joint disorder, central and peripheral neuropathies, nerve compression syndromes, multiple sclerosis, myasthenia gravis and polymyositis, systemic diseases such as hypothyroidism or severe metabolic or infectious diseases /5.® software, version 3.09 (2008).To assess the intake of zinc and selenium, the calculated values in the food surveys were adjusted and corrected for the variability of consumption among individuals in the same group using the methodology described in the Dietary Reference Intakes (DRI) and the Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) as the cut-off points for estimating the requirements of these nutrients 24]. Whe. Whe24].2). We considered the cut-off points of the WHO (1995) for eutrophic (18.5 kg/m2 and 24.9 kg/m2) and overweight (> 25 kg/m2) . In . In 26].5 kg/m2) .Major criteria: 1—localized spontaneous pain; 2—spontaneous pain or altered sensations in the expected referred pain area for the given MTrP; 3—taut, palpable band in the accessible muscle; 4—exquisite, localized tenderness in a precise point along the taut band; and 5—some measurably reduced movement range. Minor criteria: 1—reproduction of spontaneously perceived pain and altered sensations by pressure on an MTrP; 2—elicitation of a local twitch response of the muscular fibers by transverse ‘snapping’ palpation or by needle insertion into the MTrP; 3—pain relief obtained by muscle stretching or dry needling injection of the MTrP; and 4—electromyographic demonstration of spontaneous electrical activity characteristic of active loci in the tender nodule of a taut band in the muscle) 34][[34][33][[[34][33]Tissue damage found in patients with chronic pain induces the synthesis and release of inflammatory substances that increase the activity of the muscle motor endplate favoring the onset of pain 14]. Add. Add14].2+ are well documented.Recent research on the trace elements involved in antioxidant activities in patients with chronic musculoskeletal pain was identified 17]18].[18].17][.[18].17]et al. [Selenium deficiencies are still controversial 18]20][[20][18][[[20][18]et al.  found noTo the best of our knowledge, this study is the first to quantitatively evaluate the dietary intake of zinc and selenium in patients with chronic myofascial pain. Group I was observed to have a higher percentage of inadequate intake of selenium and an increased frequency of individuals who exhibit a lower zinc intake compared with the estimated average requirement.These results allow comparison with the usual consumption in the Brazilian population. Population-based studies in different Brazilian states have shown that the mean intake of zinc and selenium was 7.7 mg/day and 51.1 μg/day, respectively, and that the frequency of inadequate intake of these minerals also has values very close to those found in both groups of this study. The outcomes strongly suggest that within the Brazilian population, there is an inadequate eating habit, in which the ingestion of foods that are considered to be important sources of these nutrients does not appear to meet the EAR 39]40].[40].39][.[40].39]The values established as the EAR by the DRI do not sufficiently meet the metabolic demands imposed by oxidative stress on patients with chronic myofascial pain. Therefore, these EAR values are not applicable to this group of patients because the variables represent parameters only for healthy people.Other important factors associated with the presence of chronic musculoskeletal pain and also observed in this study are related to the practice of physical activity and obesity. In this investigation, physical inactivity was observed more frequently in patients with chronic myofascial pain, which is a risk factor associated with painful symptoms, as reported in another study . The praIn the studied sample, myofascial pain was noted to be associated with obesity, which may be a risk factor for the development of pain or a consequence of the chronicity of the disease. Though the relationship between obesity and chronic musculoskeletal pain has not been elucidated, the frequency of obesity has been identified in 37% to 65% of patients with chronic musculoskeletal pain 45]46].[46].45][.[46].45]Additional investigations concerning the concentrations of these elements in other body compartments are warranted to better define the nutritional status of these minerals, which represent a major constraint for claiming the existence of deficiencies and their temporality (acute or chronic) in the present study. Another important limitation concerns the assessment of pain intensity. Although the visual analog scale is a valid and internationally accepted method for identifying the intensity of referred pain in patients with chronic musculoskeletal pain, this assessment is affected by the strong influences of other variables  and by its subjective method; hence, the results can be unreliable.2+ and SeT. This group of patients also had a greater likelihood of inadequate intake of selenium and a higher frequency of individuals with an intake of zinc lower than the EAR. These findings are likely consequences of the inflammatory state and the need for mobilizing bodily reserves of these nutrients by an antioxidant demand.In the present study, individuals with chronic myofascial pain exhibited low concentrations of Zn


Neck pain is a common complaint in chiropractic patients. Amongst other baseline variables, numerous studies identify duration of symptoms as a strong predictor of outcome in neck pain patients. The usual time frame used for ‘acute’ onset of pain is between 0 and 4 weeks. However, the appropriateness of this time frame has been challenged for chiropractic low back pain patients. Therefore, the purpose of this study was to compare outcomes in neck pain patients with 0–2 vs 2–4 and 4–12 weeks of symptoms undergoing chiropractic treatment.This is a prospective cohort observational study with 1 year follow-up including 495 patients whose data was collected between October 2009 and March 2015. Patients were divided into high-acute (0–2 weeks), mid-acute (2–4 weeks) and subacute (4–12 weeks) corresponding to duration of their symptoms at initial treatment. Patients completed the numerical pain rating scale (NRS) and Bournemouth questionnaire for neck pain (BQN) at baseline. At follow-up time points of 1 week, 1 month, 3 months, 6 months and 1 year the NRS and BQN were completed along with the Patient Global Impression of Change (PGIC) scale. The PGIC responses were dichotomized into ‘improved’ and ‘not improved’ patients and compared between the 3 subgroups. The Chi-square test was used to compare improved patients between the 3 subgroups and the unpaired Student’s t-test was used for the NRS and BQN change scores.p = 0.015). The NRS changes scores were significantly greater for patients with 2–4 weeks of symptoms compared to 4–12 weeks of symptoms only at 1 week (p = 0.035).The proportion of patients ‘improved’ was only significantly higher for patients with symptoms of 0–2 weeks compared to 2–4 weeks at the 1 week outcome time point (The time period of 0–4 weeks of symptoms as the definition of “acute” neck pain should be maintained. Independent of the exact duration of symptoms, medium-term and long-term outcome is favourable for acute as well as subacute neck pain patients.Not applicable for prospective cohort studies. Ethics approval prior to study EK 19/2009. The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” . Neck paThe disability and economic costs associated with neck pain have a large impact on individuals, their families, healthcare systems and businesses , 14, 15.As a non-invasive treatment method, chiropractic, including both spinal manipulative therapy (SMT) and mobilization, is suggested as effective therapy for neck pain by recent research , 17–19. Aware of the need for a standardized categorization that could improve prediction of treatment outcome and allow better targeting of care, recent spinal pain research has increasingly been addressing the identification of specific patient subgroups which may have more or less favourable outcomes –25. TherThere are various ways to subdivide neck pain patients including gender, age, type of onset, aetiology , severity or duration of symptoms. According to The International Association for the Study of Pain, chronic pain is defined as pain which persists past the usual time of healing . Among dAssuming that the duration of symptoms has a relevant influence on the patient response to the treatment, it is necessary to develop a consistent definition regarding the term “acute” in neck pain research. This may lead to more specific and targeted treatments for certain patients, particularly relating to possible psychosocial factors. To find a more accurate onset of symptoms categorization, the current 0–4 week predefinition of the “acute” subgroup in neck pain patients needs to be investigated.In a study of low back pain patients receiving chiropractic treatment, differences in outcome within the acute subgroup were reported and the common definition of acute low back pain lasting 0–4 weeks was challenged by suggesting it was too long . The purThis is a follow-up study to the prospective cohort study “Predictors of outcome in neck pain patients undergoing chiropractic care: comparison of acute and chronic patients” . It is dChiropractic practices in Switzerland were asked to contribute patients to this study and 81 of the 260 Swiss chiropractors participated. Selection criteria were patients with age over 18, neck pain of any duration and no chiropractic or manual therapy in the prior 3 months. Patients with contraindications to chiropractic manipulative therapy in the form of specific pathology were excluded. These included acute fractures, tumours, infections, inflammatory arthropathies, Paget’s disease, anti-coagulation therapy, cervical spondylotic myelopathy, known unstable congenital anomalies and severe osteoporosis. For this study, only the data from patients with symptoms between 0 and 12 weeks were used resulting in a sample size of 495 patients. It is unknown what proportion of patients asked to participate in this study by their chiropractors actually agreed.For collecting the patient data, notification and instruction about the study and the study protocol were sent to all of the 260 active members of the Association of Swiss Chiropractors. During the annual mandatory postgraduate continuing education convention (CE), verbal instructions outlining the study protocol were given and workshops on the use of outcome measures in clinical practice were conducted by one of the authors. The convention was held promptly prior to the start of data collection with a request to all active members of the association to recruit patients for this study.Given this was a pragmatic study, no standardized treatment plan or treatment number was given. The chiropractors were especially asked not to change their treatment methods and there were no specific treatments excluded. However, 76% to 100% of the Swiss Chiropractors use “diversified” technique as one of their primary treatments . Other cClinical and demographic baseline data about the patients was provided by the treating chiropractor, including patient age, sex, marital status, paid employment, onset of pain due to trauma or not, the patient’s general health status, associated dizziness, whether or not the patient smokes, current pain medication, duration of complaint, number of previous episodes and if there were signs and symptoms of cervical radiculopathy.Prior to the initial treatment, each patient was requested by the office staff of the practice to complete a questionnaire assessing their individual impairment, including the numerical rating scale (NRS) for neck pain and a separate NRS for arm pain where 0 = no pain and 10 = the worst pain imaginable. Additionally, patients completed the Bournemouth Questionnaire for neck disability (BQN), which has been translated and validated into the German language .For the assessment of outcome, data from the NRS (neck and arm separately), BQN and Patient Global Impression of Change (PGIC) scale  were colOne week, 1 month, 3 months, 6 months and 1 year after the initial treatment, the patients were questioned via telephone interviews about their treatment response. The interviews were conducted by trained research assistants blinded to patient or referring chiropractor identity. The time frame when each telephone call should be done was strictly limited (i.e. 6–8 days for 1 week data) . Thus, nN = 274), mid-acute (2–4 weeks of symptoms) (N = 62), and subacute (4–12 weeks of symptoms) (N = 159). The available statistical power varied depending on the subgroups being compared and the dependent variable being used. For example, a contrast between the 274 high-acute and 159 sub-acute patients would have had 80% power to detect a between group difference in mean neck pain intensity that was as small as 0.6 points on the 0–10 NRS scale, given the standard deviations in the sample and an alpha of 0.06. For all three subgroups, baseline factors were compared using ANOVA for numerical data and the Chi-square test for categorical data. At all follow-up time points the proportions of patients ‘improved’ within each of the 3 groups were compared using the Chi-square test. For the secondary outcomes of NRS change scores (baseline score – follow-up score) and BQN change scores the ANOVA test was used for all follow-up time points as the data was normally distributed. Using the change scores rather than the actual outcome scores usually provides normally distributed data, as in this case, and thus allows the means and standard deviations to be reported.According to the duration of symptoms, the patients were divided into three subgroups of high-acute (0–2 weeks of symptoms)  vs. midacute (2–4 weeks) as well as midacute vs. subacute (4–12) neck pain patients were compared in order to identify whether the midacute patients behave more similarly to the high acute or the subacute patient groups in their treatment response. The Chi-square test was used for categorical variables (i.e. improvement) and the unpaired Student’s t-test was used for the NRS and BQN change scores.p-value ≤0.05 was considered statistically significant. For all data analysis SPSS Version 21, IBM, Armonk, New York, USA was used.A Written informed consent was obtained from all patients and ethics approval was obtained from the Canton of Zürich Switzerland ethics committee (EK 19/2009).Of the 260 active members of the Association of Swiss Chiropractors 81 (31%) contributed patients to this study. Baseline data from 495 patients with symptoms of 12 weeks or less were available and included in this study. Of these, 274 were highly acute (0–2 weeks of symptoms), 62 mid-acute (2–4 weeks of symptoms) and 159 subacute (4–12 weeks of symptoms). At the consecutive time points at 1 month, 3 months, 6 months and 1 year after the initial treatment, the numbers of included patients vary. This is a result of the limited time period when each follow-up telephone call was conducted. Some patients could not be reached during the predefined time frame but remained in the study if data from other time points was available.Baseline characteristics for all three subgroups are shown in Table p = 0.015)  (Table p = 0.039) and 1 month (p = 0.025) time points. At the 6 month and 1 year time points significant differences between the 3 subgroups were no longer found  Table , whereasThe secondary outcome data showing the change scores  of NRS (neck), and the BQN for all outcome time points are shown in Table The primary outcome measure of ‘clinically relevant improvement’ in this study only showed a significant difference between the high-acute patients (0–2 weeks of symptoms) and mid-acute patients (2–4 weeks of symptoms) at the data collection time point of 1 week with a higher proportion of the high acute patients reporting improvement. There were no further significant differences in the primary outcome for the later data collection time points detected for these two subgroups. Thus this is different from the results obtained for the chiropractic low back pain study where there were more significant differences between the patients in these two ‘acute’ time frames .Comparison of mid-acute and subacute neck pain patients showed some significant differences at the 1 week and 1 month time points, with mid-acute patients still having a significantly better outcome than subacute patients. After 6 months, no further significant differences were found between the three subgroups. Treatment outcomes level off at the 6-month follow-up time point with more than 86% of the patients in all three subgroups considered as ‘improved’. Patients with mid-acute (2–4 weeks) duration of symptoms showed no significant differences either to the high-acute (0–2 weeks) or the subacute (4–12 weeks) subgroups with their proportions of patients responding to chiropractic treatment falling between the high-acute and subacute subgroups.Analyzing the secondary outcome measures of the BQ and NRS change scores, mid-acute patients also do not differ significantly from either the high-acute subgroup or the subacute patient subgroup whilst high-acute and subacute patient cohorts report significantly different scores at almost every time point.The results of this study demonstrate a time-dependent converging of outcomes among the three subgroups. Statistically significant differences between the high-acute (0–2 weeks) and mid-acute (2–4) subgroups could only be reported 1 week after start of treatment and thus the clinical relevance of this result is negligible. The findings of this study lead to the conclusion that a categorization of acute pain according to 0–4 weeks of symptoms should be preferred to the suggested 0–2 weeks of symptoms for neck pain patients. In current research, the most often used time frame for acute neck pain uses symptom duration of 0–4 weeks .The findings of this neck pain study are surprisingly different from a parallel study on low back pain patients in similar Swiss chiropractic settings . InvestiOECD (Office for Economic Cooperation and Development) guidelines  - as welComparing the three subgroups in this study, baseline differences were registered for baseline severity of pain, mean age, general health and smoking habit. There were no significant differences detected for the other baseline factors including the baseline BQ score, patient gender as well as pain onset due to trauma or pain accompanied with radiculopathy. Several studies report the number of previous episodes as one of the most valuable predictive factors for outcome , 47, 49.From the 3 subgroups evaluated in this study, both high-acute and mid-acute patients were more likely to smoke than subacute patients. Smoking might be a risk factor for the development or exacerbation of pain. Long-time smoking may sensitize pain receptors, decrease pain tolerance, increase pain perception, and has been shown to contribute to pain persistence –57.Additional differences were found between the high-acute and subacute patients. High-acute patients reported a higher severity of pain on the NRS scale than subacute patients. However, these pain levels were obtained upon presentation for treatment and not at the actual onset of symptoms. The difference in baseline pain severity in the high-acute subgroup is most likely an effect of natural history within the acute pain phase .The last difference in the baseline characteristics comparing these 3 subgroups of neck pain patients found that a significantly higher number of patients reported below average health in the subacute group. This may correspond to the results of other studies which report an association between faster recovery and better general health , 59, 60.It is conceivable that subgrouping according to the duration of symptoms remains an artificial and somehow arbitrary way of categorization amongst a very heterogeneous acute neck pain population. The definition of acute and chronic pain by duration of symptoms is predicated on the assumption that acute pain signals a potential tissue damage, whereas chronic pain results from central as well as peripheral sensitization where pain is sustained after nociceptive inputs have diminished , 62.Subgrouping patients by means of symptom duration appears to be an easy and objective way of categorisation. However, duration-based definitions can be difficult to apply in terms of recurrent pain or pain with gradual onset. For multiple reasons, current research criticises pain definition solely by duration, suggesting pain to be a multi-dimensional concept , 62, 63.There are limitations to this study. This is not a randomized clinical trial but a prospective cohort observational study. As there is no control group in this study, outcomes of the patients cannot be definitely attributed to the treatment but may correspond with the natural course of healing process within the acute pain phase .Baseline information for this study was collected using paper questionnaires. However, follow-up data was collected via telephone interviews. Multiple studies have detected a false positive effect on outcomes with patients being more likely to report more favourable outcome to the interviewer , 65, 66.An important limitation to this study is the smaller sample size in the mid-acute patient group. Additionally, not every patient could be reached at the different follow up time points, especially at the follow up time point 1 week post treatment resulting in there being fewer patients because of the narrow time window allowed. As this was a secondary analysis on data previously collected for another study, power calculations to determine an adequate sample size for the 2–4 week subgroup were not done prior to data analysis as no additional patients could be included.It is also not known what proportion of patients asked to participate in this study by their treating chiropractor actually agreed to participate.Although the use of the Bournemouth questionnaire may appear to be a limitation in this study due to the fact it only contains 7 subscales, previous studies have found it to be a reliable and valid instrument and more responsive to change compared to the Neck Disability Index and the Neck Pain and Disability Scale , 67.The time period with 0–4 weeks of symptoms as the definition of “acute” neck pain should be maintained. Patients with a shorter period (0–2 weeks) of symptoms recover faster than patients with a longer period of symptoms (2–4 weeks) but this difference is only statistically significant at the 1 week and 1 month time periods. These results for neck pain patients are different from those obtained in the similar study investigating acute low back pain patients where the 0–2 weeks time period as the definition of ‘acute’ was recommended. Medium-term and long-term outcome is favourable for acute as well as subacute neck pain patients, independent of the exact duration of symptoms.


According to animal models, neuroinflammation is a major feature of neuropathic pain. The present findings confirm that this hypothesis is of relevance to humans. Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called “gliotransmitters,” a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile of patients with neuropathic pain. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation. Samples of CSF were collected from 2 cohorts of patients with neuropathic pain  and healthy control subjects (n = 11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously . Univariate testing with control of false discovery rate, as well as orthogonal partial least squares discriminant analysis, were used for statistical analyses. Levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23 in CSF, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared with healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in patients with fibromyalgia. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Because it has been suggested that prevalent comorbidities to chronic pain  also are associated with neuroinflammation, it will be important to determine whether neuroinflammation is a common mediator. For instance, CSF levels of classical neuropeptides, like substance P and beta-endorphin (and other endogenous opioids), have historically been studied in many different pain states.74When trying to better understand what causes and maintains NeuP, it is important to move beyond mere etiology and study the pathophysiological mechanisms involved, for instance by in-depths somatosensory phenotyping.78 Hence, central neuroimmune and neuroinflammatory mechanisms are nowadays considered to be very important in the pathophysiology of NeuP. However, it is important to stress that this has mainly been shown in preclinical models of chronic pain and that evidence in humans is less clear.60 Indeed, glial cells (at least astrocytes) from mice and monkeys are quite different from their human counterparts.71 Translating evidence from animals to humans is far from trivial,50 but a series of recent studies using a comprehensive panel of 92 inflammation-related proteins indicate the presence of low-grade systemic inflammation and neuroinflammation in chronic widespread pain conditions30 and of systemic inflammation in chronic lumbar radicular pain.55Much of our knowledge concerning the pathophysiological mechanisms of NeuP has been gained from animal experiments. It has become increasingly clear that immunocompetent glial cells, such as microglia and astrocytes, are key contributors to the pathophysiology of chronic NeuP.60 Indeed, chemokines and other pronociceptive mediators in the spinal cord have been called “gliotransmitters,”60 a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and chronic pain.Cytokines and chemokines are thought to be important mediators in the pathophysiology of NeuP, at least in preclinical models.55 and apply it to the CSF of patients with peripheral NeuP and healthy control subjects. Our hypothesis was that we would be able to determine a CSF inflammatory profile of NeuP patients and that we would be able to mirror a postulated on-going process of central neuroinflammation.The aim of the present study was to use a multiplex panel allowing the measuring of 92 inflammation-related proteins in a single runFirst, we compared NeuP patients  and healthy control subjects (cohort 1b) recruited at the same center . Then, to test the reproducibility of our results, an additional cohort of patients  with a similar pain condition but belonging to another center  were compared with cohort 1b.46For every subject in this study, intrathecal access was obtained by lumbar puncture and a 10-mL sample of CSF was taken. Details of the CSF sampling procedure have been published earlier and are not repeated here.72 all patients in cohort 1a had a least probable NeuP and patients in cohort 2 had definite NeuP. All cohort 1a patients included in this study were also participating in a clinical trial of intrathecal bolus injections of the analgesic ziconotide, CSF being sampled before the injection of ziconotide.12 Inclusion criteria were as follows: (1) patient, at least 18 years of age, experiencing chronic (≥6 months) NeuP due to trauma or surgery, who had failed on conventional pharmacological treatment; (2) average visual analogue scale pain intensity in the previous week of ≥40 mm; (3) patient capable of judgment, that is, able to understand information regarding the drug, the mode of administration, and evaluation of efficacy and side effects; (4) signed informed consent. Exclusion criteria and other registered characteristics have been extensively described elsewhere.10 All patients were or had been candidates for spinal cord stimulation (SCS).Following the criteria of Treede et al.,10Age-matched and sex-matched healthy control subjects (cohort 1b) were recruited by local advertisements at the Faculty of Health Sciences, Linköping University, Sweden.46Cohort 2 consisted of patients being treated with SCS. The SCS treatment was turned off during 2 days, whereupon a lumbar puncture was performed. Details about cohort 2 have been published elsewhere.http://links.lww.com/PAIN/A482) are simultaneously analyzed.55 The multiplex PEA was conducted using Proseek Multiplex Inflammation I  according to the manufacturer's instructions. Briefly, 1-μL sample was mixed with 3-μL incubation mixture containing 94 probe pairs (each pair consisting of 2 target-specific antibodies equipped with unique barcoded DNA oligonucleotides). The mixture was incubated at 8°C overnight. Then, 96-μL extension mixture containing PEA enzyme and polymerase chain reaction reagents was added, incubated for 5 minutes at room temperature before the plate was transferred to a thermal cycler for an extension reaction followed by 17 cycles of DNA amplification. A 96.96 Dynamic Array IFC  was prepared and primed according to the manufacturer's instructions. In a new plate, 2.8 μL of sample mixture was mixed with 7.2 μL of detection mixture from which 5 μL was loaded into the right side of the primed 96.96 Dynamic Array IFC. Five microliters of the primer pairs, unique for each assay, was loaded into the left side of the 96.96 Dynamic Array IFC, and the protein expression program was run in Fluidigm Biomark reader (Fluidigm Corporation) according to the instructions of Proseek Multiplex. Data are expressed as normalized protein expression (NPX). Values of NPX are acquired by normalizing cq values against extension control, as well as interplate control and a correction factor. They are on log2 scale. A high NPX value corresponds to a high protein concentration and can be linearized using the formula 2NPX. Also, NPX can be used for statistical multivariate analysis and express relative quantification between samples but is not an absolute quantification. Data showing the correlation between the present PEA method and an electrochemiluminescence immunoassay  for plasma CXCL1 and CXCL10 is shown in supplemental digital content 1 (available online at http://links.lww.com/PAIN/A482), where a link to the extensive background information on the method available online is also provided.We used a multiplex proximity extension assay (PEA) in which 92 proteins .When comparing the demographics of patients and healthy control subjects, data are shown as median (range), and the Mann–Whitney 55 For each protein, we tested whether there was a difference in expression levels between the 2 groups using a 2-sided Mann–Whitney U test. Performing such a large number of tests increases the risk of false discoveries. Therefore, we adjusted the P values for multiplicity using the false discovery rate (FDR) approach.7Proteins with more than 20% of values below the limit of detection were excluded from further analysis.79 The statistical workflow has been extensively described elsewhere,59 and it is consistent with the recommendations issued by Wheelock and Wheelock.79 Multivariate data analysis by projection analyzes all the variables together at the same time, taking the correlation structure of the data set into consideration, thereby favoring structure and information over “noise” and false-positive findings.25 Briefly, data were first overviewed by principal components analysis (PCA) . However, PCA was used here for the identification of outliers and deviant subgroups in the data. Then, orthogonal partial least squares discriminant analysis (OPLS-DA)  was used to identify the proteins  most responsible for class discrimination (dichotomous Y variable). The statistical significance of the regression is expressed using the P value of the cross-validated analysis of variance (CV-ANOVA). The strength of class separation can be visualized in a plot showing how each individual subject relates to the 2 first latent variables of the model (score plot). The relative importance of each protein (X variable) for class discrimination is given by the variable influence on projection (VIP), VIP >1 indicating that the variable has an above-average influence on class discrimination (Y variable).25 In this study, a VIP cutoff of 1.3 was chosen for reporting interesting class-discriminating proteins.We also used multivariate data analysis by projection with the SIMCA software version 13 .The protocol of healthy control subjects was approved by the Regional Ethics Committee in Linköping, Sweden (Dnr M136-06 and Dnr 2012/94-32). The clinical trial, from which patient data from Linköping were derived, was conjointly approved by the Swedish Medical Products Agency  and by the Regional Ethics Committee in Linköping (Dnr 2011/48-31). The study was also approved by the Regional Ethics Committee in Uppsala (01-367). The study was conducted according to the Declaration of Helsinki.P = 0.088) and sex . For detailed individual characteristics of patients of cohort 1a, see Table Patients with NeuP cohort 1a, n = 11) and healthy control subjects  did not differ significantly concerning age ; no outlier was found. Then, an OPLS-DA model was computed , showing clear separation between patients and healthy control subjects  and sex . Detailed individual characteristics for cohort 2 are shown in Table The cohort 2 patients (n = 16) did not significantly differ from the cohort 1b healthy controls (n = 11) concerning age ; no outlier was found. An OPLS-DA model was computed for cohort 2 versus cohort 1b . Eleven proteins had VIP of >1.3 and were upregulated in patients: LAPTGF-beta-1, CCL11, 4E-BP1, CXCL10, CCL23, CX3CL1, CXCL6, CD5, CCL8, CCL25, and CXCL11 .Cohorts 2 and 1b were overviewed with PCA  associated with NeuP in the other cohort as well: CXCL1, CXCL5, CXCL11, and CX3CL1.We have determined an extensive CSF inflammatory profile of patients with severe peripheral NeuP who were candidates for (cohort 1a) or had an on-going (cohort 2) treatment with SCS, compared with healthy control subjects (cohort 1b).55 but this is the first time that such a “holistic” CSF inflammatory fingerprint has been described for NeuP. We have also recently used the same panel on CSF from patients with fibromyalgia,13 with a remarkable overlap of results with the present study: all 6 proteins upregulated in both NeuP cohorts (5 of which were chemokines) were also major findings in patients with fibromyalgia. Even though it has to be acknowledged that the present study and the fibromyalgia study shared the same CSF control group, the overlap of results is nonetheless striking. Recent plasma–serum studies using the same multiplex panel55 have also shown remarkable overlaps in results (different cohorts of patients and different control groups). Statistical considerations are discussed in supplemental digital content 2 (available online at http://links.lww.com/PAIN/A482).The same panel has recently been used for serum profiling of NeuP patients,A large part of the main findings of cohort 1a could be reproduced in cohort 2, with an overlap of 55% concerning the top 11 proteins. The difference between the top 11 proteins could perhaps be due to the fact that the 2 NeuP cohorts differed concerning the presence or absence of long-term SCS treatment. Even though the 2 cohorts consisted of more or less the same category of patients, it is conceivable that long-term modulatory effects of SCS might have altered the CSF inflammatory profile of cohort 2. Even though the 2 NeuP cohorts were compared with the same control group, which is an obvious limitation, the actual overlap of results between the 2 comparisons is still noteworthy. Also, both patient cohorts were highly refractory to conventional treatment, and our results cannot be generalized to any NeuP.44 the fact that the groups did not differ statistically concerning age and sex is important to underline.Given that levels of 15 of 63 cytokines have been shown to be associated with age ,http://links.lww.com/PAIN/A482). Strikingly, levels of LAPTGF-beta-1 have also been increased in all the other studies that we have hitherto performed with the present panel (including the present study).55A description of the chemokine family, and of LAPTGF-beta-1, can be found in supplemental digital content 3  and CX3CL1  and also CXCL21, CXCL13 and other chemokines, to pain-like behavior in rodent models of NeuP has been extensively reviewed.36 Notably, CX3CL1  is thought to be involved in a prominent pathway in the development of NeuP.60 For example, in the spinal cord dorsal horn, CX3CL1 produced by neurons has been shown to interact with microglial CX3CR1, triggering an increased production of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-1b, and IL-6, causing central sensitization and increased pain-like behavior.41 Neuropathic animals have high CSF levels of CX3CL1.20 Another chemokine, CCL2, activates microglia and directly influences neurons; CCL2 can induce rapid central sensitization of dorsal horn neurons via ERK activation and enhances their excitatory synaptic transmission.28 The production of CXCL1 by spinal cord astrocytes has been shown to contribute to the maintenance of pain-like behavior in NeuP animal models,81 Moreover, CXCL1 has recently been found to be upregulated in the CSF samples of opioid-tolerant cancer patients.45 Moreover, there are indications that CXCL10 may also be involved in pain-like behavior maintenance in rodent models of NeuP.68 Neutralizing the action of chemokines, CCL2 or CX3CL1, attenuates nerve injury–induced pain-like behavior in rodents.82 Astrocytic chemokines can then modulate neuronal activity and potentiate synaptic transmission in the spinal cord excitatory pain circuitry.28 Additional chemokine references are listed in supplemental digital content 3 (available online at http://links.lww.com/PAIN/A482). The findings reported in this study are consistent with a role for chemokines in human NeuP.Chemokine receptors are potential pharmacological targets.P < 0.001; VIP = 1.06) We have previously also shown that levels of CX3CL1 were high in the CSF of patients with fibromyalgia.13(1) CX3CL1 was a main finding of cohort 2. It was not part of the main findings of cohort 1a, but a retrospective analysis revealed that it was actually upregulated in that cohort too .(2) CXCL1 was elevated in cohort 1a. It was not part of the main findings of cohort 2, but it was actually upregulated in that cohort too  CXCL10 was a main finding in both cohorts.Given the chemokines mentioned above, it is noteworthy that CX3CL1, CXCL1, and CXCL10 were part of the main findings of the present study:67; see also supplemental digital content 3 (available online at http://links.lww.com/PAIN/A482).To the best of our knowledge, among the other major findings of the study, neither CXCL6 nor CCL23 have been implicated in NeuP. In contrast, CCL11 has been investigated in at least 3 models of NeuP76 and neurotrophic factors48 are discussed in supplemental digital content 3 (available online at http://links.lww.com/PAIN/A482).“Classical” cytokines 57 it is nonetheless a frequently used concept in modern pain medicine.32 Are we perhaps measuring some aspects of central neuroinflammation in humans? This would be a major step forward for pain medicine, as evidence of central neuroinflammation has hitherto been mostly gained through animal experiments.76Although neuroinflammation is not easily defined,22 (2) activation of glial cells,80 and (3) production of inflammatory mediators.36 Neuroinflammation can contribute to central sensitizationand NeuP by chemokine18 and cytokine pathways.41Neuroinflammation can be said to have 3 characteristic components with effects on pain behavior in animal models: (1) infiltration of immune cells,39All in all, we think it is fair to say that we might have “visualized” central neuroinflammation, this being one possible mechanism associated with central sensitization, impaired descending pain inhibition, and the pain hypersensitivity characterizing chronic pain states.directly relates to the pathophysiology of NeuP  or if it is an inflammatory risk factor that was present prior to the development of NeuP . A third possibility could be that the fingerprint is a consequence of NeuP, for example, mirroring pain-related stress, physical inactivity,62 depression,75 or bad sleep.56 Of course, all 3 of these categories may play a role. Disentangling the contribution of these potentially mutually interacting factors will be very difficult. For instance, levels of peripheral IL-6 are known to be influenced by regular exercise, individuals who are inactive having higher baseline levels of this particular cytokine.62Granted that our results are valid , showing that mainly a number of chemokines were upregulated in CSF from patients compared with healthy control subjects. We find it conceivable that we might have mirrored central neuroinflammation in this very debilitating chronic pain condition. However, further studies are needed to confirm these findings, and the question of causality remains difficult to answer. Because it has been suggested that prevalent comorbidities to chronic pain also are associated with neuroinflammation, it will be important to determine unique and common mediators.The authors have no conflict of interest to declare.The study was supported by Uppsala Berzelii Technology Centre for Neurodiagnostics, with financing from the Swedish Governmental Agency for Innovation Systems (Vinnova) and the Swedish Research Council (grant no. P29797-1). The study was also financially supported by the Swedish Research Council (grant no. K2015-99x-21874-05-4), the County Council of Östergötland , and AFA Insurance (140341). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.


The aim of this study was to assess correlation between pain and degenerative bony changes on cone-beam computed tomography (CBCT) images of temporomandibular joints (TMJs).Two hundred eighty-three temporomandibular joints with degenerative bony changes were evaluated. Pain intensity  and pain duration in patients with degenerative joint disease (DJD) were also analyzed. We classified condylar bony changes on CBCT into five types: osteophyte (Osp), erosion (Ero), flattening (Fla), subchondral sclerosis (Scl), and pseudocyst (Pse).Degenerative bony changes were the most frequent in the age groups of 10~19, 20–29, and 50~59 years. The most frequent pain intensity was “none”  followed by “annoying” . The most frequent condylar bony change was Fla  followed by Ero . “Ero + Fla” was the most common combination of the bony changes (12.7%). The frequency of erosion was directly proportional to NRS, but the frequency of osteophyte was inversely proportional. The prevalence of Ero increased from onset until 2 years and gradually decreased thereafter. The prevalence of Osp, Ero, and Pse increased with age.Osp and Ero can be pain-related variables in degenerative joint disease (DJD) patients. “Six months to 2 years” may be a meaningful time point from the active, unstable phase to the stabilized late phase of DJD. Temporomandibular disorder (TMD) refers to a collective term including clinical problems that involve the masticatory muscles, the temporomandibular joint (TMJ), and associated structures . TMD is It has been controversial whether degenerative bony changes of TMJ can be related to the onset, progression, or regression of TMJ-related signs and symptoms , 9. The Two hundred and fifty patients who visited the dental hospital from September 2013 to March 2015 complaining of TMJ pains, TMJ sounds, or mouth opening limitation were evaluated. Conventional radiological evaluations  and CBCT examinations were performed. Two hundred one patients (165 women and 36 men) with degenerative bony changes on their conventional radiographies and CBCT images were selected. We excluded normal condyles of DJD patients and finally evaluated 283 condyles.Pain intensity and pain duration were examined. Pain intensity was evaluated with the numeric rating scale (NRS). We asked patients’ average pain intensity of the past 3 days. NRS is 0 to 10 verbal rating scale where “0” was no pain and “10” was the worst pain possible. We classified it into five grades . In addition, we asked patients the onset time of their pain.Osteophytes: marginal bony outgrowths on the condyleErosion: an area of decreased density or discontinuity or irregularity of the cortical boneFlattening: a flat bony contour deviating from the convex formSclerosis: an area of increased density of cortical bone extending into the bone marrowPseudocysts: well-circumscribed osteolytic adjacent subcortical bone area without cortical destructionAll subjects were scanned with Alphard-3030  with P-mode, operating at 80 kV, 8 mA with a voxel of 0.30 mm. The primary reconstruction of the raw data was restricted to the TMJ region  using Xelis dental program. The long axial view of the examined condyle was traced with the TMJ tool, and the software generated lateral and frontal cross-sectional reconstructions perpendicular and parallel to the long axis of the condyle, respectively. The thickness of the image slices was 1 mm, and the distance between slices was 1 mm for both lateral and frontal reconstructions. The reconstructed images were analyzed by three well-trained dentists. Right and left TMJs were examined separately, resulting in a total of 283 TMJs. Comparing the sagittal, coronal, and 3D images, we classified degenerative bony changes into five types: osteophytes, erosion, flattening, subchondral sclerosis, and pseudocysts [P values less than 0.05 were considered statistically significant. Statistical evaluation of the data was performed using the IBM SPSS Statistics ver. 22.0 for Windows Simple regression analysis was used to assess the correlation of pain intensity and age on the occurrence of degenerative bone changes. This study was performed with 201 patients. The percentage of women (82%) were higher than men (18%) (Table Figure Table Accumulative number and percentage of degenerative bony change in degenerative condyles are presented in Table Figure Figure Several studies reported that the progression and the severity of bony changes on the TMJ increased with age –15. On tThe intermediate phase of bony destruction in TMJ lasts on average 6 months to 1 year . In the Generally, bone deformation characterized in DJD is osteophytes, erosion, flattening, sclerosis, and pseudocysts. Each type of bony change occurs in different stages of DJD and has different clinicopathological meanings . As a coEven though pain has occurred only in one side, degenerative condylar changes can be detected on both sides Fig. . One thiErosion is a radiographic clue that an active destructive process may be occurring, whereas osteophyte is an indication that the condyle has adapted to degenerative changes produced in the past . In thisThe prevalence of erosion increased from onset until 2 years and gradually decreased thereafter Fig. . This reWhereas some previous studies reported that there was poor correlation between bony change and pain , 14, ourOur study has several limitations such as the limited sample size. Moreover, we evaluated only the first-visit results and excluded the follow-up results. To verify the significant relationships between pain and radiographic findings, further well-organized studies will be needed in the future.The present study may find a correlation between pain intensity and degenerative bony changes on CBCT images. Osteophyte and erosion can be pain-related variables in DJD patients. Six months to 2 years may be a meaningful time point from active, unstable phase to stabilized late phase of DJD.