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Background: Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis. Aim: To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization. Methods: An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100). Outcomes: Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no). Results: Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P =.01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P <.001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale–Revised, Cohen's d = 0.68; all P <.05) and poorer mental health (higher scores: Patient Health Questionnaire–9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P <.001; Generalized Anxiety Disorder–7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P =.002). Anatomic findings at the time of surgery did not significantly differ between the groups. Clinical Implications: Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis. Strengths and Limitations: A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function. Conclusion: Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Aerobic exercise may be an effective treatment for knee osteoarthritis and central sensitization, but no interventional studies have examined its effects. In this study, the patient showed improvement in central sensitization, pain, and autonomic nervous system activity after aerobic exercise using an arm ergometer. [ABSTRACT FROM AUTHOR]

Study Design A retrospective analysis. Purpose To investigate the occurrence of central sensitization (CS) in patients with osteoporotic vertebral compression fractures (OVCFs) and identify the association between CS and residual back pain (RBP). Overview of Literature RBP is a vexing complication that affects 6.3%–17.0% of patients with OVCFs who underwent percutaneous vertebroplasty (PVP). Given the negative effect of RBP on patients’ psychological and physiological statuses, efforts to preoperatively select patients who are at risk for RBP development have a high priority to offer additional treatment and minimize this complication. Methods Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP. Results Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p

Background: Acute low back pain has a high prevalence, and when persisting into chronicity, it results in enormous socio-economic consequences. Sensory preferences may be key factors in predicting central sensitization as the main mechanism of nociplastic pain and chronicity. Objectives: Build a model to predict central sensitization symptoms using sensory profiles based on the PROGRESS framework. Methods: A Prognostic Model Research study was carried out to predict central sensitization symptoms at 12 weeks, using baseline sensory profiles, based on 114 patients with acute low back pain. Independent variables were sensory profiles, state and trait anxiety, age, duration, pain severity, depressive symptoms, and pain catastrophizing. Results: This model, based on continuous data, significantly predicts central sensitization symptoms at 12 weeks. It contains two significantly contributing variables: sensory profile Sensory Sensitive (unstandardized B-value = 0.42; p = 0.01) and trait anxiety (unstandardized B-value = 0.53; p ≤ 0.001). The model has a predictive value of R2 = 0.38. Conclusions: This model significantly predicts central sensitization symptoms based on sensory profile Sensory Sensitive and trait anxiety. This model may be a useful tool to intervene in a bottom–up and top–down approaches to prevent chronicity in clinical practice, including individual sensory preferences and behavioral responses to sensory stimulation in rehabilitation strategies. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective analysis. Purpose: To investigate the occurrence of central sensitization (CS) in patients with osteoporotic vertebral compression fractures (OVCFs) and identify the association between CS and residual back pain (RBP). Overview of Literature: RBP is a vexing complication that affects 6.3%–17.0% of patients with OVCFs who underwent percutaneous vertebroplasty (PVP). Given the negative effect of RBP on patients' psychological and physiological statuses, efforts to preoperatively select patients who are at risk for RBP development have a high priority to offer additional treatment and minimize this complication. Methods: Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP. Results: Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05). Conclusions: Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication. [ABSTRACT FROM AUTHOR]

BackgroundMusculoskeletal pain, a possible marker of central sensitization, is associated with higher prevalence of lower urinary tract symptoms (LUTS) among older men. We investigated whether musculoskeletal pain is associated with LUTS progression.MethodsParticipants were 5 569 men age ≥65 years enrolled in the prospective, multicenter Osteoporotic Fractures in Men (MrOS) Study. Self-reported musculoskeletal pain within 12 months before baseline was categorized as any pain and multilocation pain. Pain interference within 4 weeks of baseline was assessed with the SF-12 questionnaire. LUTS were assessed repeatedly with the American Urological Association Symptom Index (AUA-SI). Men with severe LUTS at baseline were excluded. LUTS progression was defined as the first occurrence of a ≥4-point AUA-SI increase during a 2-year follow-up interval. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using multivariable pooled logistic regression.ResultsLUTS progression was 37% higher among men with any musculoskeletal pain compared with men without pain (IRR 1.37, 95% CI: 1.21, 1.54). Positive associations were also observed between LUTS progression and pain at 1 (IRR 1.31, 95% CI: 1.13, 1.48) and ≥2 locations (IRR 1.42, 95% CI: 1.24, 1.60). Compared with men without pain interference, men with quite a bit/extreme pain interference were most likely to experience LUTS progression (minimal interference IRR 1.15, 95% CI: 1.03, 1.26; moderate interference IRR 1.28, 95% CI: 1.11, 1.45; quite a bit/extreme interference IRR 1.47, 95% CI: 1.22, 1.71).ConclusionsAmong men initially without severe LUTS, musculoskeletal pain is associated with an increased risk of LUTS progression. Studies using validated measures of central sensitization and LUTS progression among men are warranted.

Key Clinical Message Aerobic exercise may be an effective treatment for knee osteoarthritis and central sensitization, but no interventional studies have examined its effects. In this study, the patient showed improvement in central sensitization, pain, and autonomic nervous system activity after aerobic exercise using an arm ergometer.

Study Design: Multicenter prospective study. Objective: The influence of central sensitization (CS) on neurological symptoms and surgical outcomes in patients with degenerative cervical myelopathy (DCM) remains unknown. This study aimed to investigate the effects of preoperative CS on surgical outcomes of patients with DCM following posterior decompression surgery. Methods: 77 consecutive patients with DCM (mean age 67.1) who received posterior decompression surgery were included in this study. The participants completed CS inventory (CSI) scores and the following patient-reported outcome measures (PROMs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for cervical myelopathy and JOA cervical myelopathy evaluation questionnaire (JOACMEQ) for cervical spinal diseases. The association of preoperative CSI scores with preoperative and postoperative PROMs was analyzed, and their changes were statistically evaluated. Results: The preoperative CSI score was significantly decreased at 12 months postoperatively, and it was significantly associated with the JOA score and JOACMEQ preoperatively and at 12 months postoperatively. However, no significant association was observed between preoperative CSI and the postoperative change of any PROMs at 12 months. The posterior decompression surgery significantly improved the JOA scores and 'lower extremity function' and 'quality of life (QOL)' domains of the JOACMEQ, independent of the severity of preoperative CSI score. Multiple regression analysis demonstrated that preoperative CSI was significantly associated with the 'QOL' domain of JOACMEQ and original JOA score at 12 months postoperatively. Conclusion: The CSI score can be an auxiliary indicator of surgical outcomes of patients with DCM following posterior decompression surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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BACKGROUND AND OBJECTIVES: The presence of central sensitization (CS) in people with chronic neck pain requires clarification, as does the possible disparities between genders. Therefore, this study aimed to evaluate the presence of CS in chronic neck pain according to gender. METHODS: Cross-sectional study with the participation of 260 adults (18-59 years old) with chronic neck pain, carried out between September 2022 and September 2023. Instruments were applied to collect sociodemographic profile, pain characteristics, cervical functional disability and presence of SC. The software SPSS 23.0 was used for comparative analyzes. RESULTS: Regarding disparities between genders, there were no differences in the intensity of pain and cervical functional disability (p=0.134 and p=0.277, respectively). However, SC was higher in women (43.5 ± 14.0; p=0.003). In females, CS was related to "pain interference" in the aspects of walking (r=0.311; p=0.001), relationships with people (r=0.309; p=0.001), appreciation of life (r=0.321; p= 0.001) and with cervical functional disability (r=0.570; p=0.001). In males, CS was related to "pain interference" in aspects such as general activity (r=0.311; p=0.008), mood (r=0.376; p=0.001), walking (r=0.313; p= 0.007), relationships with people (r=0.477; p=0.001), sleep (r=0.321; p=0.006), appreciation of life (r=0.427 p=0.001) and functional disability (r=0.667; p

Three categories of pain mechanisms are recognized as contributing to pain perception: nociceptive, neuropathic, and nociplastic (ie, central nervous system augmented pain processing). We use validated questionnaires to identify pain mechanisms in Urologic Chronic Pelvic Pain Syndrome (UCCPS) patients (n = 568, female = 378, male = 190) taking part in the Symptom Patterns Study of the Multidisciplinary Approach to the study of chronic Pelvic Pain Research Network. A cutoff score of 12 on the painDETECT questionnaire (-1 to 38) was used to classify patients into the neuropathic category while the median score of 7 on the fibromyalgia survey criteria (0-31) was used to classify patients into the nociplastic category. Categories were compared on demographic, clinical, psychosocial, psychophysical and medication variables. At baseline, 43% of UCPPS patients were classified as nociceptive-only, 8% as neuropathic only, 27% as nociceptive+nociplastic, and 22% as neuropathic+nociplastic. Across outcomes nociceptive-only patients had the least severe symptoms and neuropathic+nociplastic patients the most severe. Neuropathic pain was associated with genital pain and/or sensitivity on pelvic exam, while nociplastic pain was associated with comorbid pain conditions, psychosocial difficulties, and increased pressure pain sensitivity outside the pelvis. A self-report method classifying individuals on pain mechanisms reveals clinical differences that could inform clinical trials and novel targets for treatment. PERSPECTIVE: This article presents differences in clinical characteristics based on a simple self-report method of classifying pain mechanisms for Urologic Chronic Pelvic Pain Syndrome patients. This method can be easily applied to other chronic pain conditions and may be useful for exploring pathophysiology in pain subtypes.

To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments. SR with meta-analysis Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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ObjectiveTo examine the cross-sectional association of ascending pain mechanisms, implicated in pain sensitization, and descending pain modulation with pain patterns and unpredictability of pain.MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee osteoarthritis. Peripheral and central ascending pain mechanisms were assessed using quantitative sensory tests, pressure pain thresholds using a handheld pressure algometer (knee/peripheral and wrist/central), and temporal summation using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation using pressure pain thresholds and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant Osteoarthritis Pain questionnaire: 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of quantitative sensory test measures to pain patterns using regression models with generalized estimating equations.ResultsThere were 2,794 participants (mean age 63.9 years, body mass index 29.5 kg/m2 , and 57% female). Lower pain sensitization by wrist pressure pain threshold (odds ratio [OR] 0.80 [95% confidence interval (95% CI) 0.68, 0.93]) and adequate conditioned pain modulation (OR 1.45 [95% CI 1.10, 1.92]) were associated with having constant ± intermittent pain compared with intermittent pain only. Higher pain sensitization (by pressure pain thresholds and temporal summation) was associated with a higher likelihood of unpredictable pain.ConclusionKnee pain patterns appear to be related to peripheral ± central facilitated ascending pain mechanisms and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.

AimsFeatures of central sensitization (CS) are present in almost all chronic pain conditions, including painful urinary conditions and back pain. Recently CS was proposed as a mechanism of nonpainful lower urinary tract symptoms (LUTS). Using musculoskeletal pain as an indicator of CS, we investigated whether the prevalence of musculoskeletal pain is greater among community-dwelling men with moderate or severe LUTS compared to those with mild LUTS.MethodsWe conducted a cross-sectional study of 5966 men ≥65 years who attended the Osteoporotic Fractures in Men Study baseline visit. LUTS were assessed with the American Urological Association Symptom Index (AUA-SI) and categorized as none/mild (0-7), moderate (8-19), or severe (≥20). Self-reported back, neck, hip, or knee pain within the 12 months before baseline was categorized as any pain and multilocation pain. We tested our hypothesis using odds ratios (OR) and 95% confidence intervals (CI) estimated from multivariable logistic regression models.ResultsThe adjusted odds of any pain were higher among men with moderate (OR 1.49, 95% CI: 1.29-1.72) and severe LUTS (OR 1.76, 95% CI: 1.28-2.40) compared to those with no/mild LUTS. The adjusted odds of pain at ≥ 2 locations were 69% higher among men with moderate (OR 1.69, 95% CI: 1.45-196) and more than double among men with severe LUTS (OR 2.24, 95% CI: 1.62-3.10) compared to men with no/mild LUTS.ConclusionsMusculoskeletal pain, especially at multiple locations, is associated with greater LUTS severity among older men. CS may represent a novel shared mechanism of pain and LUTS.

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. [ABSTRACT FROM AUTHOR]

Objective: The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain. Design: A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. The results of the different reviews were statistically synthesized through a random-effect meta-analysis, of all standardized mean differences and the corresponding 95% confidence interval reported by each study. Results: For mechanical hyperalgesia, the meta-meta-analysis of three meta-analyses revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate-quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low-quality evidence. Conclusion: Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate-quality evidence, as well as temporal summation and conditioned pain modulation with low-quality evidence. However, its effects are limited only to immediate and short-term. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Cross-sectional study. Interdisciplinary outpatient rehabilitation clinic for back and neck pain. 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). Not applicable. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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Abstract 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.

Fibromyalgia and opioid use disorder (OUD) are highly impactful chronic illnesses with substantially overlapping psychosocial, biological, and clinical features. Little previous research has examined interactions between fibromyalgia and OUD. Limiting such research has been the previous requirement of a clinical examination to diagnose fibromyalgia. The 2011 American College of Rheumatology Fibromyalgia Survey (ACR-FMS) is a validated self-report instrument with high sensitivity and specificity for fibromyalgia intended to enable fibromyalgia research in settings where a clinical examination is impractical. The present observational study uses the ACR-FMS to determine whether fibromyalgia affects odds of acknowledging pain-related OUD exacerbations among a sample of participants with pain and OUD. Participants with pain and OUD (n 5 125) were recruited from an academic substance use treatment facility. The ACR-FMS, along with an original scale measuring pain-related OUD exacerbation—the Pain-related OUD Exacerbation Scale—was administered through an electronic survey. The factor structure, internal consistency, and construct validity of Pain-related OUD Exacerbation Scale were tested. In addition, descriptive analyses, multiple hierarchical linear regression, ordinal logistic regression, and multinomial logistic regression analyses were performed. Although all participants had pain, those with fibromyalgia demonstrated significantly greater odds of acknowledging pain-related OUD exacerbations. Pain-related OUD Exacerbation Scale was found to have a single-factor solution, strong internal consistency, and construct validity. This study provides first evidence of fibromyalgia as a risk factor for pain-related exacerbation of OUD and introduces a new scale with promising psychometric properties to measure pain-related OUD exacerbation. [ABSTRACT FROM AUTHOR]

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Abstract Background Objective Methods Results Conclusion 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.The present study is the first to employ a validated surrogate measure to describe central sensitization in a clinical sample with AUD.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.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.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine the relation of pain sensitization to altered motor activity in knee OA as assessed by hamstrings muscle co-contraction during maximal effort knee extension.DesignMedial, lateral, and overall hamstring co-contraction was assessed in the Multicenter Osteoarthritis (MOST) Study cohort using electromyography during isokinetic knee extension at 60°/second. Mechanical temporal summation of pain (TS) was assessed at the right wrist and pressure pain thresholds (PPT) were assessed at the patellae; PPTs were categorized into sex-specific tertiles. Muscle co-contraction was categorized into age- and sex-specific tertiles. We evaluated the relation of measures of sensitization to muscle co-contraction using a generalized logistic regression model.Results1633 participants were included: mean age and BMI was 67.3 ± 7.7 years and 30.3 ± 5.6 kg/m2, respectively; 58% were female. Presence of TS was associated with higher overall (OR 1.3, 95% confidence interval (CI) (1.0-1.8)), medial (1.4 (1.0-1.9), and lateral (1.3 (1.0, 1.9)) hamstring co-contraction. The lowest PPT tertile (greater sensitivity) was associated with higher overall (1.5 (1.0, 2.3)) and medial (1.5 (1.0, 2.3)) hamstring co-contraction compared with those in the highest PPT tertile.ConclusionGreater pain sensitization, as assessed by presence of TS at the wrist and low patellar PPT, was associated with greater overall and medial hamstring co-contraction during knee extension. This provides support to the possibility that peripheral and/or central nervous system alterations may not only affect pain sensitivity, but also motor function.

ObjectiveSensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches.MethodsFunctional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined.ResultsAcross repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure.ConclusionsThe results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.

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. [ABSTRACT FROM AUTHOR]

Aims: Links between emotional state and the bladder have long been recognized, as psychological comorbidity is a common feature of overactive bladder (OAB). However, how psychological factors might contribute to the development and severity of OAB remains unclear. Therefore, we sought to examine the effect of anxiety on OAB with a specific focus on bladder hypersensitivity. Methods: In a sample of 120 adult women with OAB, we compared those with at least mild anxiety (PROMIS Anxiety score ≥55) to those with lower anxiety. Analyses focused on patient‐reported questionnaires assessing urinary symptom severity and quality of life, psychological stress symptoms, general somatic symptoms, and results of quantitative sensory testing (QST), including temporal summation to heat pain (TSP). TSP was used to index elevated C‐fiber responsiveness (i.e., central sensitization). Results: Thirty‐six (30%) women had at least mild anxiety. While there were no group differences for urinary symptom severity, more anxious women reported worse OAB‐specific quality of life, greater psychological stress burden, higher stress reactivity, and greater somatic symptoms. On QST, there were no differences between anxiety groups for pain threshold (43.6 ± 3.1°C vs. 44.0 ± 3.1°C, p = 0.6) and tolerance (47.3 ± 1.5°C vs. 47.4 ± 1.6°C, p = 0.7). However, those with anxiety had significantly higher TSP than those without anxiety (6.0 ± 4.8 vs. 3.7 ± 3.9, p = 0.006), indicating greater central sensitization. Conclusions: Women with OAB and at least mild anxiety symptoms reported greater psychosocial burdens (i.e., psychological stress, stress reactivity, OAB‐specific QOL) and somatic symptom severity and demonstrated greater central sensitization on QST than those without anxiety. These findings support the hypothesis that anxiety and psychological stress impact hypersensitivity mechanisms that may underlie and contribute to OAB, although further research is needed to better understand how and to what extent. [ABSTRACT FROM AUTHOR]

Females demonstrate heightened central sensitization (CS), a risk factor for chronic pain characterized by enhanced responsivity of central nervous system nociceptors to normal or subthreshold input. Sleep disruption increases pain sensitivity, but sex has rarely been evaluated as a moderator and few experiments have measured CS. We evaluated whether two nights of sleep disruption alter CS measures of secondary hyperalgesia and mechanical temporal summation in a sex-dependent manner. We also evaluated differences in measures of pain sensitivity. Seventy-nine healthy adults (female n = 46) participated in a randomized crossover experiment comparing two consecutive nights of eight pseudorandomly distributed forced awakenings (FA [-200 min sleep time]) against two nights of undisturbed sleep (US). We conducted sensory testing the mornings following Night 2; the heat-capsaicin pain model was used to induce secondary hyperalgesia. FA reduced total sleep time (REM and NREM Stage 3) more profoundly in males. We observed divergent, sex-dependent effects of FA on secondary hyperalgesia and temporal summation. FA significantly increased secondary hyperalgesia in males and significantly increased temporal summation in females. Sex differences were not attributable to differential sleep loss in males. FA also significantly reduced heat-pain threshold and cold pressor pain tolerance, independently of sex. Sleep disruption enhances different pain facilitatory measures of CS in males and females suggesting that sleep disturbance may increase risk for chronic pain in males and females via distinct pathways. Findings have implications for understanding sex differences in chronic pain and investigating sleep in chronic pain prevention efforts.

Abstract Interventions based on pain education and self-management are dependent on factors such as attention, memory, concentration, and executive function. Objective To explore the relationship between cognitive performance and the variables pain intensity, central sensitization, catastrophizing, and hypervigilance in women diagnosed with chronic pain-related TMD. Methodology This is a cross-sectional study. A total of 33 women (mean age: 38±4.6 years; range: 18 to 66 years) with chronic pain-related TMD (myalgia and/or arthralgia) diagnosed according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Specific questionnaires were used to evaluate cognitive performance, overall pain intensity, central sensitization, hypervigilance, and pain catastrophizing. The data were analyzed using Pearson’s correlation coefficient and backward stepwise multiple linear regression (statistical significance at 5% alpha). Results Approximately 53% of the study sample showed decreased cognitive performance. High central sensitization, hypervigilance, and pain catastrophizing were observed. A significant negative correlation was observed between cognitive performance and hypervigilance (p=.003, r=−.49), cognitive performance and catastrophizing (p

Background: To investigate the relationship between cutaneous allodynia (CA) and kinesiophobia, gastrointestinal system (GIS) symptom severity, physical activity, and disability, and to determine whether CA, pain, and disability were influencing factors for kinesiophobia, GIS symptoms, and physical activity in individuals with migraine. Methods: The study included 144 individuals with migraine. CA, kinesiophobia, GIS symptoms, physical activity level, and migraine-related disability were evaluated with the Allodynia Symptom Checklist, the Tampa Kinesiophobia Scale (TKS), the Gastrointestinal Symptom Rating Scale (GSRS), the International Physical Activity Questionnaire-7, and the Migraine Disability Assessment Scale (MIDAS), respectively. Results: The CA severity was only associated with TKS (r = 0.515; P < 0.001), GSRS-total (r = 0.336; P < 0.001), GSRS-abdominal pain (r = 0.323; P < 0.001), GSRS-indigestion (r = 0.257; P = 0.002), GSRS-constipation (r = 0.371; P < 0.001), and MIDAS scores (r = 0.178; P = 0.033). Attack frequency (P = 0.015), attack duration (P = 0.035) and presence of CA (P < 0.001) were risk factors for kinesiophobia. Attack frequency (P = 0.027) and presence of CA (P = 0.004) were risk factors for GIS symptoms. Conclusions: There was a relationship between the CA and kinesiophobia, GIS symptoms, and disability. CA and attack frequency were found to be risk factors for kinesiophobia and GIS symptoms. Migraine patients with CA should be assessed in terms of kinesiophobia, GIS, and disability. Lifestyle changes such as exercise and dietary changes and/or pharmacological treatment options for CA may increase success in migraine management. [ABSTRACT FROM AUTHOR]

Background: Resting-state functional connectivity (rs-FC) may aid in understanding the link between painmodulating brain regions and the descending pain modulatory system (DPMS) in fibromyalgia (FM). This study investigated whether the differences in rs-FC of the primary somatosensory cortex in responders and non-responders to the conditioned pain modulation test (CPM-test) are related to pain, sleep quality, central sensitization, and the impact of FM on quality of life. Methods: This cross-sectional study included 33 females with FM. rs-FC was assessed by functional magnetic resonance imaging. Change in the numerical pain scale during the CPM-test assessed the DPMS function. Subjects were classified either as non-responders (i.e., DPMS dysfunction, n = 13) or responders (n = 20) to CPM-test. A generalized linear model (GLM) and a receiver operating characteristic (ROC) curve analysis were performed to check the accuracy of the rs-FC to differentiate each group. Results: Non-responders showed a decreased rs-FC between the left somatosensory cortex (S1) and the periaqueductal gray (PAG) (P < 0.001). The GLM analysis revealed that the S1-PAG rs-FC in the left-brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores. ROC curve analysis showed that left S1-PAG rs-FC offers a sensitivity and specificity of 85% or higher (area under the curve, 0.78, 95% confidence interval, 0.63–0.94) to discriminate who does/does not respond to the CPM-test. Conclusions: These results support using the rs-FC patterns in the left S1-PAG as a marker for predicting CPM-test response, which may aid in treatment individualization in FM patients. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague–Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24- hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation. Mechanical allodynia was measured using the von Frey test for 0–4 hours (early phase) and 24–28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions: Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation. [ABSTRACT FROM AUTHOR]

Abstract Background Very positive effects have been described in the application of pain neuroscience education (PNE) to chronic pain and migraine. However, there are few data on the applicability of this therapeutic approach in actual clinical practice in a primary care (PC) setting. The aim of this study was to explore the efficacy in fibromyalgia (FM) of an intervention based on PNE and exercise compared to treatment as usual (TAU). Methods Pragmatic nonrandomised controlled trial set in 5 healthcare centres and one physiotherapy centre in PC. Fifty-three women with FM (2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia) were studied, 35 in the intervention group (IG) and 18 in the control group (CG). The women in the IG were interviewed individually and then received 6 weekly sessions plus one review session (1 month later): those in the CG received their TAU. The subject assignation to the CG or the IG was determined according to their availability to attend the sessions. They all filled in several questionnaires (prior to and 1 year after the intervention) to evaluate the impact of FM in their daily lives, catastrophism, anxiety and depression, severity and impact of pain in daily personal performance and functional capacity. Results The reductions (improvements) in the scores of all tests (baseline-final) were greater in the IG (p

Abstract Background Musculoskeletal pain patients present similar pain characteristics regardless of the clinical diagnosis. PainDETECT questionnaire is useful for screening neuropathic-like symptoms in many musculoskeletal conditions. However, no previous studies compared pain phenotypes of patients with musculoskeletal pain using the painDETECT. Therefore, the current study aimed to compare the pain characteristics of patients with musculoskeletal pain classified according to the painDETECT as nociceptive pain, unclear, and neuropathic-like symptoms. Methods A cross-sectional study was conducted in 308 participants with musculoskeletal pain. Demographic and clinical characteristics of the participants were examined. Neuropathic-like symptoms, pain intensity, pain area, Central Sensitization-related sign and symptoms, functional limitation, and conditioned pain modulation were assessed in patients with musculoskeletal pain. Independent one-way analysis of variance (ANOVA) was used to test for between-group differences for the outcome measures with continuous variables and Pearson chi-square test verified between-group differences on the efficiency of the conditioned pain modulation. Results Participants had a mean age of 52.21 (±15.01) years old and 220 (71.42%) were females. One hundred seventy-three (56.16%) participants present nociceptive pain, 69 (22.40%) unclear, and 66 (21.42%) neuropathic-like symptoms. A one-way ANOVA showed differences for the pain intensity [F (2,305) = 20.097; p

Chronic overlapping pain conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This "centralized pain" phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here, we used 3 cohorts, including patients with urologic chronic pelvic pain syndrome, a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified 2 general factors in all 3 cohorts, one characterized by a broad increased sensitivity to internal somatic sensations,environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity, and one characterized by constitutional symptoms-Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the urologic chronic pelvic pain syndrome cohort found the same 2-factor structure at month 6 and 1 year, suggesting that the 2-factor structure is reproducible over time. In secondary analyses, we found that Generalized Sensory Sensitivity particularly is associated with the presence of comorbid COPCs, whereas SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent an important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.

Latent sensitization is a model of chronic pain in which an injury triggers a period of hyperalgesia followed by an apparent recovery, but in which pain sensitization persists but is suppressed by opioid and adrenergic receptors. One important characteristic of latent sensitization is that hyperalgesia can be triggered by acute stress. To determine whether the effect of stress is mimicked by the activation of corticotropin-releasing factor (CRF) signaling in the brain, rats with latent sensitization induced by injecting complete Freund's adjuvant (CFA, 50 μl) in one hind paw were given an intracerebroventricular (i.c.v.) injection of CRF. The i.c.v. injection of CRF (0.6 μg, 10 μl), but not saline, induced bilateral mechanical hyperalgesia in rats with latent sensitization. In contrast, CRF i.c.v. did not induce hyperalgesia in rats without latent sensitization (injected with saline in the hind paw). To determine whether descending pain inhibition mediates the suppression of hyperalgesia in latent sensitization, rats with CFA-induced latent sensitization received an intrathecal injection of lidocaine (10%, 1 μl) at the cervical-thoracic spinal cord to produce a spinal block. Lidocaine-injected rats, but not rats injected intrathecally with saline, developed bilateral mechanical hyperalgesia. Intrathecal lidocaine did not induce hyperalgesia in rats without latent sensitization (injected with saline in the hind paw). These results show that i.c.v. CRF mimicked the hyperalgesic response triggered by stress during latent sensitization, possibly by blocking inhibitory spinal descending signals that suppress hyperalgesia.

Simple Summary: Persistent pain after breast cancer treatment is still under research due to its complex and multifactorial underlying pathogenesis, including phycological factors. Further research is needed to elucidate more information about the factors that cause and perpetuate this pain. Thus, this study defined the influence of psychosocial and psychological factors on breast cancer survivors who report pain and those who do not. The psychosocial factors assessed were those that are associated with a central sensitization process, and the psychological factors were pain catastrophizing, fear of movement, anxiety and depression. Hence, the psychosocial symptom clusters were identified related to the clinical features of pain or to not reporting pain, which may encourage health clinicians to establish a customized biopsychosocial model focused on the management of pain-catastrophizing thoughts and fear of movement. Furthermore, anxiety and depression should be detected early by health professionals and referred to psychologists to be managed. The frequency of a high Central Sensitization Inventory (CSI) total score and the prevalence of pain have already been established among breast cancer survivors (BCS). However, the psychological factors' influence based on the clinical features of pain is still unknown, as well as BCS characteristics with no pain. Thus, our main aim was to evaluate the presence of a high CSI total score in BCS with pain and compare it with BCS without pain and to evaluate the influence of psychosocial factors. A cross-sectional comparative study was designed to compare BCS with nociceptive pain (n = 19), pain with neuropathic features (n = 19) or no pain (n = 19), classified by the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). CSI, pain catastrophizing, fear of movement, anxiety and depression symptoms were analyzed and compared among the three groups. The CSI total score was higher in both BCS pain groups compared to BCS without pain, but there were no statistical differences between the pain groups. The same observation was made when comparing pain catastrophizing. The neuropathic feature group showed greater levels of fear of movement, anxiety and depression compared to the no pain group. Thus, CS-psychosocial associated comorbidities and pain-catastrophizing thoughts were more prevalent among BCS with pain, regardless of the clinical features of pain. BCS with neuropathic pain features showed greater psychological disturbances. [ABSTRACT FROM AUTHOR]

Objective: Patients with rheumatoid arthritis (RA) commonly demonstrate disordered pain processing associated with high pain sensitization. Pain sensitization is often assessed using quantitative sensory testing (QST), which is burdensome to patients. The self-administered Fibromyalgia Survey Questionnaire (FSQ) has been proposed as a low-burden, surrogate measure of central pain sensitization. We examined the correlation between FSQ and QST in patients with active RA.Methods: Participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort underwent FSQ and QST evaluation at enrollment. QST measures included pressure pain threshold (PPT) at the thumb, trapezius, wrist, and knee; temporal summation (TS) at the wrist and arm; and conditioned pain modulation (CPM). Partial Spearman correlation between FSQ and each QST measure was assessed, adjusted for demographic factors, study site, disease characteristics, and pain catastrophizing. Sensitivity analyses included (1) stratified analysis by sex and (2) evaluation of how each component of FSQ associates with the QST measures.Results: Among 285 participants with active RA, FSQ was weakly but statistically significantly correlated with PPT (r range = -0.31 to -0.21), and TS (r range = 0.13-0.15) at all sites in unadjusted analyses. After adjustment, statistically significant correlations persisted for TS at the wrist and PPT at all sites (except the thumb). Sensitivity analyses did not identify differences in association based on sex or with individual FSQ components.Conclusion: FSQ and QST were correlated among participants with active RA, but the strength of association was weak. QST and FSQ are not interchangeable measures of pain sensitization. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In many patients with axial spondyloarthritis (axSpA), pain persists despite anti-inflammatory medication. Quantitative sensory testing (QST) indirectly assesses altered somatosensory function, though its clinical practicality is limited. The Central Sensitisation Inventory (CSI) could be an alternative in the initial assessment of central sensitisation (CS). This study aimed to investigate the value of the CSI in evaluating CS in patients with axSpA by (1) assessing somatosensory function related to CS with QST and (2) exploring associations between CSI, QST, patient and disease characteristics and pain-related psychosocial factors., Methods: Consecutive outpatients from the Groningen Leeuwarden AxSpA cohort underwent QST, including pressure pain threshold (PPT), temporal summation (TS) and conditioned pain modulation (CPM). Participants completed questionnaires assessing CS (CSI), illness perception (Revised Illness Perception Questionnaire, IPQ-R), pain-related worrying (Pain Catastrophising Scale, PCS), fatigue (Modified Fatigue Impact Scale, MFIS), anxiety/depression (Hospital Anxiety and Depression Scale, HADS) and coping. QST measurements were stratified for CSI≥40., Results: 201 patients with axSpA were included; 63% male, 64% radiographic axSpA, median symptom duration 12 years (IQR 5-24), mean Axial Spondyloarthritis Disease Activity Score 2.1±1.0. Patients with CSI≥40 had significantly lower PPTs and higher TS than CSI<40 (p<0.004). No significant differences in CPM were observed. In multivariable linear regression, sex, PCS, IPQ-R Identity, MFIS and HADS anxiety were independently associated with CSI (78% explained variance)., Conclusion: In this large cross-sectional study in patients with axSpA, the CSI appears as a useful initial CS assessment questionnaire. When CSI scores indicate CS, considering pain-related psychosocial factors is important. These results emphasise the need for a biopsychosocial approach to manage chronic pain in patients with axSpA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Characterize heart rate and cardiac autonomic response to painful stimulus on neck pain., Methods: Twenty-five individuals with neck pain and 25 healthy subjects were included. Heart rate variability and heart rate were assessed in the conditioned pain modulation test at pretest rest, during testing and in recovery. Heart rate variability indices were obtained using linear and nonlinear methods., Results: No significant differences were observed between groups regarding heart rate and the linear methods (p > 0.05). However, significant difference was observed between groups regarding nonlinear methods (standard deviation of the instantaneous variability of beat-to-beat interval variability, p = 0.005) CONCLUSIONS: Individuals with chronic neck pain showed autonomic responses similar to those of their healthy counterparts during the conditioning stimulus., Competing Interests: Declaration of competing interest We hereby certify that no party with a direct interest in the results of the research that supports this article has or will offer benefits to us or any organization with which we are affiliated., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Estimates of the prevalence of Long COVID in the United States or worldwide are imprecise, but millions of people are thought to be affected. No effective treatment exists for the often devastating symptoms of Long COVID. Central Sensitization has been postulated as a causal/explanatory mechanism for developing Long COVID. No treatment to date has targeted Central Sensitization. The present cross-sectional study describes the first 140 patients treated in a multi-component treatment program that targets Central Sensitization to reduce symptom burden, improve functioning, and lower the psychological distress observed in these patients., Methods: 140 patients diagnosed with Long COVID after an extensive medical evaluation were assessed for function, depression, and pain catastrophizing using questionnaires and patient satisfaction measures after completion of a 16-h Cognitive Behavioral Therapy treatment program focused on Central Sensitization., Results: Upon admission, patients diagnosed with Long COVID were significantly impaired in their ability to function due to their symptoms. Further, 70% of the patients were depressed. Pain catastrophizing was observed in up to 20% of patients., Conclusion: Patient satisfaction measures were high for the sample at the end of the treatment program suggesting that a multicomponent treatment program targeting Central Sensitization is acceptable to patients. Further research is needed to explore the effectiveness and durability of this treatment approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)