Current understanding of nociplastic pain.

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.

Nociplastic Pain and Pain-Motivated Drinking in Alcohol Use Disorder.

Heavy chronic alcohol use may produce pain amplification through neurochemical and neuroplastic changes at multiple levels of the nervous system. Similar changes are thought to underlie nociplastic pain. The American College of Rheumatology Fibromyalgia Survey has been used as a surrogate for nociplastic pain, including among individuals with alcohol use disorder (AUD). However, studies linking nociplastic pain to pain-motivated drinking are lacking. The present study aimed to determine if nociplastic pain is associated with pain-motivated drinking in AUD. To achieve this aim, a new scale-the Pain-Motivated Drinking Scale (PMDS)-was developed to measure how often participants were motivated by pain to drink alcohol. Measurement properties of this new scale were determined, including its factor structure, internal consistency reliability, and construct validity. In this cross-sectional observational study, participants with AUD (n = 138) were consecutively recruited from the patient pool at an academic addiction treatment facility. Seventy-two percent (95, 72.0%) reported they drank alcohol "to get relief from physical pain" at least some of the time, and over forty-two percent (56, 42.4%) reported pain relief motivated their drinking at least half of the time. PMDS had a single-factor structure, strong internal consistency reliability, and construct validity. A multiple hierarchical linear regression was run to determine if nociplastic pain was associated with pain-motivated drinking. Nociplastic pain was associated with PMDS even after controlling for potential confounders and pain severity. These findings suggest nociplastic pain is uniquely associated with pain-motivated drinking in AUD. PERSPECTIVE: Nociplastic pain is independently associated with pain-motivated drinking in alcohol use disorder (AUD). The Pain-Motivated Drinking Scale (PMDS) is a new scale to measure how often people drink to cope with pain. PMDS has promising psychometric properties. Nociplastic pain may be uniquely associated with pain-motivated drinking in AUD.

Clinical features of chronic primary pain in individuals presenting painful temporomandibular disorder and comorbidities.

BACKGROUND: The diagnosis of chronic primary pain (CPP), according to the recently released International Classification of Disease (ICD-11) criteria, refers to conditions with complex aetiologies. CPP is characterized by specific clinical features such as generalized sensory hypersensitivity and widespread pain, and is associated with functional disability and emotional distress. OBJECTIVE: This study investigated clinical features of CPP in individuals with painful temporomandibular disorders (TMD) and comorbidities (fibromyalgia, migraine and/or tension-type headache). METHODS: This cross-sectional study was conducted with a sample of 129 individuals. Painful TMD, fibromyalgia and primary headaches were evaluated based on well-established international criteria. Generalized sensory hypersensitivity was assessed using psychophysical tests. Symptoms of anxiety and depression were assessed by the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9. The Central Sensitization Inventory was applied to assess central sensitization-related symptoms and the Pittsburg Sleep Quality Index to evaluate the quality of sleep. The presence of widespread pain was assessed using a body map. The sample was stratified into three groups: control (n = 25), TMD-painful TMD only (n = 35) and TMD + Cm-painful TMD and comorbidities (n = 69). Statistical analysis was performed using one-way ANOVA, chi-squared test and ANCOVA, considering gender as a covariate (α = .05). RESULTS: Compared to controls, individuals presenting painful TMD and comorbidities showed lower pressure pain thresholds in all evaluated areas (p ≤ .012) and a higher number of painful areas in the body (p = .001). They presented more symptoms of anxiety (p = .040) and depression (p = .018), and a higher score in the Central Sensitization Inventory (p ≤ .006) than the other groups. CONCLUSION: Individuals with painful TMD and comorbidities presented more clinical features of CPP compared to those affected by TMD only.

Does manual therapy meaningfully change quantitative sensory testing and patient reported outcome measures in patients with musculoskeletal impairments related to the spine?: A 'trustworthy' systematic review and meta-analysis.

OBJECTIVES: To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments. DESIGN: SR with meta-analysis. LITERATURE SEARCH: Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro. METHODS: This SR included English-language randomized clinical trials (RCTs) involving manual therapy to treat spinal impairments in adults. The primary outcome was pressure pain thresholds (PPTs). To synthesize RCTs with high confidence in estimated effects using the GRADE, RCTs with questionable prospective, external, and internal validity, and high risk of bias (RoB) were excluded. RESULTS: Following title and abstract screening, 89 full-text RCTs were reviewed. Twenty-two studies included the criteria of interest. Sixteen were not prospectively registered, two contained discussion/conclusions judged to be inconsistent with the registry, and one was rated as having a high RoB. Three studies met the inclusion criteria; heterogeneous interventions and locations for PPT testing prevented synthesis into practice recommendations. The two studies with high confidence in estimated effects had small effect sizes, and one study had confidence intervals that crossed zero for the outcome measures of interest. DISCUSSION: Standardized PPT testing, as a potential measure of centrally mediated pain, could provide clues regarding the mechanisms of manual therapy or help identify/refine research questions. CONCLUSION: High-quality RCTs could not be synthesized into strong conclusions secondary to the dissimilarity in research designs. Future research regarding quantitative sensory testing should develop RCTs with high confidence in estimated effects that can be translated into strong recommendations.

Widespread Pain With Nociplastic Features is an Independent Predictor of Low Physical Activity in People with Multiple Sclerosis.

Exploring the relationship between underlying pain mechanisms and physical activity could inform interventions to optimize physical activity in persons with multiple sclerosis (PwMS). This cross-sectional nationwide survey examined whether pain phenotype is a significant predictor of self-reported physical activity in PwMS. The study included 938 persons with a self-reported diagnosis of MS (93% reported neurologist-diagnosed MS) who completed surveys of demographic, clinical information, pain intensity, indicators of underlying pain mechanisms (Fibromyalgia Survey Criteria and painDETECT), and physical activity (Godin Leisure-Time Exercise Questionnaire). Responses were used to categorize pain phenotypes as widespread pain with nociplastic features (WPNF), neuropathic, nociceptive, or mixed (neuropathic/WPNF). Following current physical activity guidelines, self-reported physical activity was categorized as active or insufficiently active/sedentary. Applying multivariable logistic regression, participants with no chronic pain had 2.30 higher odds of being physically active when compared to participants with chronic mixed pain. Similarly, participants with neuropathic and nociceptive pain had, respectively, 1.90 and 1.66 higher odds of being physically active compared to individuals with mixed pain. Higher scores on the fibromyalgia survey criteria (operationalized in this study as an indicator of WPNF) were a significant independent predictor of insufficient physical activity (OR = .93, P < .01). Findings indicate that experience and phenotype of chronic pain, in particular WPNF, are associated with physical inactivity in PwMS. This suggests that assessing pain phenotype may be important to identify individuals at risk of inadequate physical activity and may guide the tailoring of behavioral therapeutic approaches to help PwMS achieve the recommended level of physical activity. PERSPECTIVE: This study examines the association between pain mechanism and physical activity in multiple sclerosis. These findings highlight the possibility that a basic screening for pain mechanism could offer clinically useful information without requiring extensive neurobiological phenotyping and may inform the development of behavioral interventions to enhance physical activity in multiple sclerosis.

Does the painDETECT questionnaire identify impaired conditioned pain modulation in people with musculoskeletal pain? - a diagnostic accuracy study.

BACKGROUND: People with neuropathic-like symptoms had more unfavourable pain features than people with nociceptive. Moreover, deficient conditioned pain modulation is common in people with neuropathic-like symptoms. PainDETECT questionnaire have been used to assess the central sensitisation sign and symptoms. However, whether the painDETECT questionnaire can identify the conditioned pain modulation's impairment is still unknown. Therefore, the current study aimed to evaluate the diagnostic accuracy of the painDETECT questionnaire in detecting the impairment of conditioned pain modulation in people with musculoskeletal pain. METHODS: We conducted a diagnostic accuracy comparing the painDETECT questionnaire (index method) with the cold pressor test, the psychophysical test used to assess the conditioned pain modulation (reference standard). We determined diagnostic accuracy by calculating sensitivity, specificity, predictive values, and likely hood ratios. RESULTS: We retrospectively enrolled 308 people with musculoskeletal pain in outpatient departments. Most participants were female (n 20 = 220, 71.4%) and had a mean age of 52.2 (± 15.0) years. One hundred seventy-three (56.1%) participants were classified as nociceptive pain, 69 (22.4%) as unclear, and 66 (21.4%) as neuropathic-like symptoms. According to the cold pressor test, 60 (19.4%) participants presented impairment of conditioned pain modulation. The cutoff point of 12 of the painDETECT questionnaire showed values of diagnostic accuracy below 70% compared to the cold pressor test, except for a negative predictive value [76.9 95% Confidence Interval (CI) 71.7 to 81.5]. The cutoff point 19 showed high specificity (78.6%, 95% CI 73.0 to 83.5), high negative predictive value (80.5%, 95% CI 78.1 to 82.7), and accuracy of 67.5% compared to the cold pressor test. CONCLUSION: The painDETECT questionnaire seems valuable for ruling out people with musculoskeletal pain and impairment of conditioned pain modulation.

[Holistic treatment of endometriosis]. / Ganzheitliche Behandlung der Endometriose.

BACKGROUND: The pain phenomena caused by endometriosis are manifold. In addition to nociceptive pain there is also a nociplastic reaction with central sensitization. Atypical symptoms, such as acyclic lower abdominal pain, radiating pain, nonspecific bladder and intestinal complaints or even depression increasingly occur in addition to the classical cyclic complaints, such as severe dysmenorrhea, cyclic lower abdominal pain, dyspareunia, dysuria and dyschezia. Due to the diffuse range of symptoms, affected patients often consult not just gynecologists but also specialists from other disciplines (internal medicine, gastroenterology, orthopedics, pain therapy, psychology etc.). OBJECTIVE: The complexity of endometriosis is presented. The resulting approaches to multimodal interdisciplinary holistic treatment are described. RESULTS: Interdisciplinary concepts should be involved in the optimal treatment of endometriosis patients along with hormonal and surgical treatment, mostly under the supervision of a gynecologist and pain management, dietary changes, psychological support and physiotherapeutic management should also be included. This article provides an overview of possible treatment strategies for chronic symptomatic endometriosis. CONCLUSION: Based on multimodal treatment strategies and regarding the complex pathophysiological alterations of this disease, the complex complaints that significantly impair the quality of life of endometriosis patients can be greatly improved.

Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms.

There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through numerous mechanisms such as direct tissue damage and inflammation, the induction of excessive immunologic activity, and the development of peripheral or central sensitization. Treating infections might relieve pain by attenuating these processes, but a growing body of literature suggests that some antimicrobial therapies confer analgesic effects, including for nociceptive and neuropathic pain symptoms, and affective components of pain. The analgesic mechanisms of antimicrobials are indirect, but might be conceptualized into two broad categories: 1) the reduction of the infectious burden and associated pro-inflammatory processes; and 2) the inhibition of signaling processes (e.g., enzymatic and cytokine activity) necessary for nociception and maladaptive neuroplastic changes via off-target effects (unintended binding sites). For the former, there is evidence that symptoms of chronic low back pain (when associated with Modic type 1 changes), irritable bowel syndrome, inflammatory bowel disease, chronic pelvic pain, and functional dyspepsia might be improved after antibiotic treatment, though significant questions remain regarding specific regimens and dose, and which subpopulations are most likely to benefit. For the latter, there is evidence that several antimicrobial classes and medications exert analgesic effects independent of their reduction of infectious burden, and these include cephalosporins, ribavirin, chloroquine derivatives, rapalogues, minocycline, dapsone, and piscidin-1. This article aims to comprehensively review the existing literature for antimicrobial agents that have demonstrated analgesic efficacy in preclinical or clinical studies.

Antimicrobial therapies for chronic pain (part 2): the prevention and treatment of chronic pain.

The discovery and development of antimicrobial therapies represents one of the most significant advancements in modern medicine. Although the primary therapeutic intent of antimicrobials is to eliminate their target pathogens, several antimicrobials have been shown to provide analgesia as a secondary benefit. Antimicrobials have demonstrated analgesic effects in conditions that involve dysbiosis or potential subclinical infection (e.g ., chronic low back pain with Modic type 1 changes; chronic prostatitis/chronic pelvic pain; irritable bowel syndrome; inflammatory bowel disease; functional gastrointestinal disorders/dyspepsia; myalgic encephalomyelitis/chronic fatigue syndrome), and might even prevent the chronification of pain after acute infections that are associated with excessive systemic inflammation (e.g ., post COVID-19 condition/long Covid, rheumatic fever). Clinical studies often assess the analgesic effects of antimicrobial therapies in an observational manner, without the ability to identify causative relationships, and significant gaps in the understanding remain regarding the analgesic potential of antimicrobials. Numerous interrelated patient-specific, antimicrobial-specific, and disease-specific factors altogether contribute to the perception and experience of pain, and each of these requires further study. Given worldwide concerns regarding antimicrobial resistance, antimicrobials must continue to be used judiciously and are unlikely to be repurposed as primary analgesic medications. However, when equipoise exists among several antimicrobial treatment options, the potential analgesic benefits of certain antimicrobial agents might be a valuable aspect to consider in clinical decision-making. This article (the second in a two-part series) aims to comprehensively review the evidence on the prevention and treatment of chronic pain using antimicrobial therapies and suggest a framework for future studies on this topic.

Comparison of the effects of transcutaneous electrical nerve stimulation and interferential current therapies in central sensitization in patients with knee osteoarthritis.

Background: This study is primarily aimed to determine whether transcutaneous electrical nerve stimulation (TENS) and interferential current (IFC) treatments have any effect on central sensitization (CS) in patients with knee osteoarthritis (OA) and to investigate which treatment is more effective. Methods: In this randomized controlled trial, 80 patients were randomized into four treatment groups: TENS, Plasebo-TENS, IFC, and Plasebo-IFC. All interventions were applied 5 times a week for 2 weeks. Primary outcome was pressure pain threshold (PPT), which is accepted as the objective indicator of CS, at the painful knee and at the shoulder as a painless distant point. Other outcome measures were the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index, Timed Up and Go Test, pain catastrophizing scale, Beck Depression Inventory, and Tampa Scale of Kinesiophobia. Results: All assessment parameters were improved, without a significant difference among the groups except PPT. PPT scores were significantly improved in TENS and IFC groups when compared with the sham groups at 2 weeks and 3 months. In addition, this improvement was even more pronounced in the TENS group. Multivariable logistic regression analysis showed that the patient's inclusion in the TENS group, an initial high PPT, and an initial low VAS score were independent risk factors for improvement in the PPT. Conclusions: This study shows that TENS and IFC reduced pain sensitivity as compared to placebo groups in patients with knee OA. This effect was more pronounced in the TENS group.

Central sensitization in alcohol use disorder: correlates of pain, addiction and health-related quality of life.

BACKGROUND: Central sensitization is an important mechanism underlying many chronic pain conditions. Chronic pain and alcohol use disorder (AUD) are highly comorbid. Despite great scientific interest in brain mechanisms linking chronic pain and AUD, progress has been impeded by difficulty assessing central sensitization in AUD. OBJECTIVE: The present study is the first to employ a validated surrogate measure to describe central sensitization in a clinical sample with AUD. METHODS: Participants with AUD (n = 99) were recruited from an academic addiction treatment center. A well-established surrogate measure of central sensitization, The American College of Rheumatology Fibromyalgia Survey Criteria (ACRFMS) was administered. Participants also responded to questions about quality of life (RAND-36), and AUD. Descriptive analyses and Spearman's rho correlations were performed. RESULTS: Chronic pain and evidence of central sensitization were prevalent. Greater central sensitization was associated with worse health-related quality of life. Participants higher in central sensitization expressed greater endorsement of pain as a reason for AUD onset, maintenance, escalation, treatment delay, and relapse. CONCLUSION: The present study bolsters prior assertions that AUD and chronic pain might compound one another via progressive sensitization of shared brain circuitry. These results may inform future mechanistic research and precision AUD treatment.

[Nociplastic pain in research and practice : Overview of biopsychosocial principles, possibilities and difficulties]. / Noziplastischer Schmerz in Forschung und Praxis : Übersicht über biopsychosoziale Grundlagen, Möglichkeiten und Schwierigkeiten.

Traditionally, two mechanistic pain categories were distinguished: nociceptive and neuropathic pain. After the definitions of these two mechanistic descriptors were refined more precisely in the International Association for the Study of Pain (IASP) taxonomy in 2011, a large group of patients remained whose pain could not be assigned to either of the two categories. Nociplastic pain was therefore proposed as a third mechanistic descriptor in 2016. This review article presents the current state of the integration of nociplastic pain into research and clinical practice. In particular, the possibilities and difficulties of applying this concept are addressed from a human and animal experimental research perspective.

The Neurophysiological Lesion: A Scoping Review.

Objective: The purpose of this study was to examine the extent of the literature on the neurophysiological lesion as referenced in functional neurology. Methods: A literature search was performed within the period from 2010 to March 2021. Search terms included central sensitization, central sensitivity syndrome, nociplastic pain, cold hyperalgesia, heat hyperalgesia, mechanical hyperalgesia, dynamic mechanical allodynia, temporal summation, spatial summation, and descending inhibition. A qualitative synthesis summarized the research findings, including clinical conditions and effect of spinal manipulation. Results: There were 30 studies, which included 7 high-level studies (meta-analysis or systematic reviews), 22 randomized controlled studies, and 1 scoping review. The findings suggest the existence of the changes in the central integrated state of a population of neurons with various disorders, experimentally induced stimulation, and treatment. The current literature suggests plasticity of the central integrative state (CIS) with the onset of pathologies and the changes in the CIS with different conservative nonpharmacologic treatments. Conclusions: This review suggests changes in the resting state of the CIS of a population of neurons that exist in the physiologic lesion may change in response to various therapies, including manipulative therapy. The findings from this review provide support of the hypothesis that nonpharmacologic conservative care may affect the neurophysiological lesion. However, studies were heterogeneous and evidence was lacking in the translation of targeting the therapies to distinct neuronal areas for clinical outcomes to treat specific disease states.

The effect of graded motor imagery training on pain, functional performance, motor imagery skills, and kinesiophobia after total knee arthroplasty: randomized controlled trial.

Background: The aim was to investigate the effect of graded motor imagery (GMI) added to rehabilitation on pain, functional performance, motor imagery ability, and kinesiophobia in individuals with total knee arthroplasty (TKA). Methods: Individuals scheduled for unilateral TKA were randomized to one of two groups: control (traditional rehabilitation, n = 9) and GMI (traditional rehabilitation + GMI, n = 9) groups. The primary outcome measures were the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were knee range of motion, muscle strength, the timed up and go test, mental chronometer, Movement Imagery Questionnaire-3, lateralization performance, Central Sensitization Inventory, Pain Catastrophizing Scale, and Tampa Kinesiophobia Scale. Evaluations were made before and 6 weeks after surgery. Results: Activity and resting pain were significantly reduced in the GMI group compared to the control group (P < 0.001 and P = 0.004, respectively). Movement Imagery Questionnaire-3 scores and accuracy of lateralization performance also showed significant improvement (P = 0.037 and P = 0.015, respectively). The Pain Catastrophizing Scale and Tampa Kinesiophobia Scale scores were also significantly decreased in the GMI group compared to the control group (P = 0.039 and P = 0.009, respectively). However, GMI did not differ significantly in WOMAC scores, range of motion, muscle strength, timed up and go test and Central Sensitization Inventory scores compared to the control group (P > 0.05). Conclusions: GMI improved pain, motor imagery ability, pain catastrophizing, and kinesiophobia in the acute period after TKA.

Does Central Sensitization Influence Outcomes of Lumbar Discectomy Surgery in Patients With Lumbar Disc Herniation? A Multicenter Prospective Study.

STUDY DESIGN: Multicenter prospective study. OBJECTIVE: Patients with central sensitization (CS) are reported to be at high risk of poor outcomes after spinal surgery. However, the influence of CS on surgical outcomes for lumbar disc herniation (LDH) remains unknown. This study aimed to examine the association between preoperative CS and surgical outcomes in LDH patients. METHODS: A total of 100 consecutive patients with LDH (mean age 51.2) who underwent lumbar surgery were included in this study. The extent of CS was evaluated using the central sensitization inventory (CSI), a screening tool for CS-related symptoms. The patients completed the following CSI and clinical outcome assessments (COAs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for back pain, JOA back pain evaluation questionnaire (JOABPEQ), and Oswestry Disability Index (ODI). The association between preoperative CSI scores, and preoperative and postoperative COAs was analyzed, and the postoperative changes were statistically evaluated. RESULTS: The preoperative CSI score significantly decreased 12 months postoperatively. Preoperative CSI scores showed a significant correlation with most COAs; however, a significant correlation was only identified in the social function and mental health domains of JOABPEC postoperatively. Higher preoperative CSI showed worse preoperative COAs; however, all COAs significantly improved regardless of CSI severity. There were no significant differences in any COAs among the CSI severity groups 12 months postoperatively. CONCLUSIONS: The results of this study showed that lumbar surgeries significantly improved the COAs regardless of preoperative severity of CS in patients with LDH.

Women with fibromyalgia (ACR criteria) compared with women diagnosed by doctors and women with osteoarthritis: Cross-sectional study using functional and clinical variables.

PURPOSE: To compare functional and clinical variables of women with fibromyalgia (American College of Rheumatology [ACR] criteria) vs women diagnosed by doctors and women with knee osteoarthritis (KOA). METHODS: This is a cross-sectional study. We used clinical measures, namely, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Fibromyalgia Impact Questionnaire-Revised (FIQ-R), Numerical Pain Rating Scale (NPRS), Central Sensitization Inventory (CSI), Pain-Related Catastrophizing Thoughts Scale (PCTS), and functional measures, such as Sit-to-Stand (STS) test, and Timed Up and Go (TUG) test. RESULTS: The sample consisted of 91 participants divided into 3 groups: participants with KOA (n = 30), fibromyalgia diagnosed according to the ACR (FM-ACR, n = 31), and fibromyalgia according to the medical diagnosis (FM-Med, n = 30). In the comparisons, we observed a significant difference (P < 0.05) and a large effect size (d ≥ 0.8), between all groups, in the WPI, WPI + SSS, FIQ-R domains, CSI, and PCTS. We did not observe significant values in the correlations between the clinical variables, SST, and TUG test. CONCLUSION: People with fibromyalgia according, to the ACR, have higher levels of widespread pain, symptom severity, global impact on quality of life, central sensitization, and catastrophizing compared with people with knee OA and people with clinical fibromyalgia diagnosis not confirmed by the ACR diagnostic criteria.

Pelvic pain comorbidities associated with quality of life after endometriosis surgery.

BACKGROUND: After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. OBJECTIVE: This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. STUDY DESIGN: This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. RESULTS: The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (ß=3.19), pelvic floor myalgia (ß=2.44), and Patient Health Questionnaire 9 depression score (ß=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. CONCLUSION: Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.

Effectiveness of motor control exercise, aerobic walking, and muscle strengthening programs in improving outcomes in a subgroup of population with chronic low back pain positive for central sensitization: a study protocol for a randomized controlled trial.

BACKGROUND: The role of pain sensitivity in the development and maintenance of chronic pain states, impaired executive functioning, and patient recovery is being investigated. Conditioned pain modulation (CPM) is widely used to measure musculoskeletal pain associated with central sensitization (CS). Despite the recommendations of many reviews and clinical practice guidelines that exercise programs reduce pain and disability, the overall confidence in these results is considered "critically low." The "active ingredient" of exercise programs and the dominant factor influencing CPM remain largely unknown. The objectives of this trial are to determine: • If different exercises cause different results on the CPM in a subgroup of people with chronic low back pain (CLBP) who are labeled as having CS pain, • If a program of exercise interventions for 12 weeks would alter executive functioning, quality of life (QoL), disability, and pain in persons with CLBP. • The relationship between patient characteristics, executive functions, CPM, and QoL METHODS: The trial is a randomized, controlled, multi-center study with four experimental groups and one healthy control group. Both the researchers and the people in the study will be blinded to the results. This paper describes the protocol for a trial examining the effects of 12-week individualized, twice-weekly exercise sessions lasting 30 to 60 min in persons with CLBP, who are positive for CS. Participants will be randomized to receive either patient education with motor control exercises (MCE), superficial strengthening (SS), aerobic exercises (AE), or patient education alone. Another group comprised of healthy volunteers will serve as controls. The primary outcomes are changes in CPM outcomes as measured by the cold pressor test (CPT). The secondary objectives are to evaluate executive functioning, pain, disability, quality of life, and spine muscle strength. The outcomes will be measured at 3 months and at a 6-month follow-up. DISCUSSION: The outcomes of the study will help in gaining more information and evidence about exercise-induced analgesia from the perspective of CPM. Measuring exercise outcomes will aid in scientifically prescribing exercise prescriptions in people with CLBP. The study outcomes will also assist in identifying the characteristics of individuals who will respond or respond indifferently to exercises. Investigating the relationship between the study's various outcomes could provide information for future trials. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI) identifier: CTRI/2022/03/041143. Registered on 16 March 2022.

Cough Sensitivity to Several External Triggers is Associated with Multiple Non-respiratory Symptoms.

PURPOSE: Enhanced responsiveness to external triggers is thought to reflect hypersensitivity of the cough reflex. It may involve an enhanced sensitivity of the afferent nerves in the airways and/or an abnormal processing of the afferent information by the central nervous system (CNS). The CNS processing of cough has been shown to involve the same regions as those in symptom amplification, a phenomenon that often manifests as multiple symptoms. The main purpose of the present study was to define whether the presence of several cough triggers is associated with multiple symptoms. METHODS: 2131 subjects with current cough responding to two email surveys filled in a comprehensive questionnaire about social background, lifestyle, general health, doctors' diagnoses and visits, symptoms, and medication. Multiple symptoms was defined as three or more non-respiratory, non-mental symptoms. RESULTS: A carefully controlled multiple regression analysis revealed that the number of cough triggers was the only cough characteristic associating with multiple non-respiratory, non-mental symptoms [aOR 1.15 (1.12-1.19) per one trigger, p < 0.001]. Among the 268 subjects with current cough both in the first survey and in the follow-up survey 12 months later, the repeatability of the trigger sum was good with an intraclass correlation coefficient of 0.80 (0.75-0.84). CONCLUSION: The association between the number of the cough triggers and multiple symptoms suggests that the CNS component of cough hypersensitivity may be a manifestation of non-specific alteration in the CNS interpretation of various body sensations. The number of cough triggers is a repeatable measure of cough sensitivity.

Widespread Proprioceptive Acuity Impairment in Chronic Back Pain: A Cross-sectional Study.

OBJECTIVE: To investigate whether proprioceptive accuracy measured with the Joint Position Sense (JPS) in patients with chronic neck and low back pain is impaired exclusively in affected areas or also in distant areas, not affected by pain. DESIGN: Cross-sectional study. SETTING: Interdisciplinary outpatient rehabilitation clinic for back and neck pain. PARTICIPANTS: Patients with chronic neck pain (n=30), patients with chronic low back pain (n=30), and age- and sex-matched asymptomatic control subjects (n=30; N=90). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients and asymptomatic control subjects completed a test procedure for the JPS of the cervical spine, lumbar spine, and ankle in a randomized order. Between group differences were analyzed with the univariate analysis of variance and associations of the JPS with clinical features using the Pearson's correlation coefficient. RESULTS: Both patients with chronic neck pain (P<.001) and patients with chronic low back pain (P<.01) differed significantly from asymptomatic controls in the JPS of the cervical spine, lumbar spine and ankle joint, regardless of the painful area. No difference was shown between patient groups (P>.05). An association of the JPS with clinical characteristics, however, could not be shown. CONCLUSION: These results suggest widespread impairment of proprioceptive accuracy in patients with chronic and low back pain and a role for central sensorimotor processes in musculoskeletal pain conditions.