The effect of six-week regular stretching exercises on regional and distant pain sensitivity: an experimental longitudinal study on healthy adults.

BACKGROUND: Stretching exercises are widely used for pain relief and show positive effects on musculoskeletal, nociplastic and neuropathic pain; the magnitude of altered pain sensitivity responses following regular stretching is currently unknown. This study aimed to investigate the effect of six weeks of regular stretching exercise on regional and widespread pain sensitivity and range of motion and the effect of stretching cessation on regional and widespread pain sensitivity and range of motion. METHODS: An experimental single-blind longitudinal repeated measures study. Twenty-six healthy adults were recruited. Regional and distant pressure pain thresholds and passive knee extension range of motion were measured at three points: before (baseline) and after six weeks (post-stretch) of daily bilateral hamstring stretching exercises and following four weeks of cessation (post-cessation) from stretching exercises. RESULTS: Participants had a mean ± standard deviation (range) age of 23.8 ± 2.1 (21-30) years. There was a 36.7% increase in regional (p = 0.003), an 18.7% increase in distant pressure pain thresholds (p = 0.042) and a 3.6% increase in range of motion (p = 0.002) between baseline and post-stretch measures. No statistically significant differences were found for regional (p = 1.000) or distant pressure pain thresholds (p = 1.000), or range of motion (p = 1.000) between post-stretch and post-cessation. A 41.2% increase in distant pressure pain thresholds (p = 0.001), a 15.4% increase in regional pressure pain thresholds from baseline to post-cessation (p = 0.127) and a 3.6% increase in passive knee extension range of motion (p = 0.005) were found from baseline to post-cessation. CONCLUSIONS: Six weeks of regular stretching exercises significantly decreased regional and widespread pain sensitivity. Moreover, the results showed that the hypoalgesic effect of stretching on regional and widespread pain sensitivity persisted following four weeks of cessation. The results further support the rationale of adding stretching exercises to rehabilitation efforts for patients experiencing nociceptive, nociplastic, and neuropathic pain. However, further research is needed to investigate how the long-term effects of stretching exercises compare with no treatment in clinical populations. TRIAL REGISTRATION: The trial was registered June 1st, 2021 at ClinicalTrials.gov (Trial registration number NCT04919681).

Association of Pain Intensity and Sensitivity with Suicidal Ideation in Adolescents with Depressive Disorder.

Purpose: The purpose of this study was to further explore the association of pain intensity and sensitivity with suicidal ideation in adolescents with depressive disorder by comparing the differences in pain intensity and sensitivity between adolescent patients with depressive disorders and healthy controls. Patients and Methods: A consecutive enrollment method was used to select 158 adolescent patients with depressive disorders from three hospitals in Anhui Province as the MDD group, and 47 healthy adolescents were recruited as the Control group. The subjects' suicidal ideation was assessed using the Positive and Negative Suicide Ideation scale (PANSI), and the intensity of somatic pain was assessed using the Numerical Rating Scale-11 (NRS-11). Subjects were assessed for forearm and tibial pain sensitivity using a hand-held pressure pain instrument, and experimental pain sensitivity measures included pressure pain threshold (PPT) and pressure pain tolerance (PTO). Differences in pain intensity and sensitivity between the MDD group and the Control group were compared, and the association of pain intensity and sensitivity with suicidal ideation was analyzed. Results: The incidence of physical pain in adolescent depressive disorder was higher at 88.6%, which was significantly higher than the Control group (P<0.001), and the pain intensity in the MDD group (3.77±2.48) was significantly higher than the Control group (0.617±0.99) (P <0.001).The Pain tolerance was significantly higher in the MDD group (forearm 105.37 ± 41.46; tibia 121.29 ± 41.60) than in the Control group (forearm 91.92 ± 37.62; tibia 105.47 ± 35.52) (P < 0.05).Linear regression analysis showed that the greater the pain intensity and pain tolerance, the higher the total PANSI score.Binary logistic regression showed that pain intensity was an influencing factor for suicidal ideation. Conclusion: Adolescents with depressive disorders have higher pain intensity and lower pain sensitivity than healthy adolescents. Increased pain intensity and pain tolerance were positively correlated with suicidal ideation.

Neuronal activation patterns during self-referential pain imagination.

In clinical assessments and pain therapy, patients are asked to imagine themselves in pain. However, the underlying neuronal processes remain poorly understood. Prior research has focused on empathy for pain or reported small sample sizes. Thus, the present study aimed to promote the neurobiological understanding of self-referential pain imagination. We hypothesised to find activation contrasts (pain vs. no pain) across pain-related areas and expected two of the most prominent predictors of chronic pain, pain sensitivity (PS) and locus of control (LoC), to be moderators. In an fMRI study, N = 82 participants completed a pain imagination task, in which they were asked to imagine themselves in painful and non-painful situations presented in the form of pictures and texts. After each trial, they were instructed to give painfulness ratings. As a laboratory measure of PS, electrical pain thresholds were assessed. A questionnaire was completed to measure LoC. Across presentation modes we found activity contrasts in previously pain-related regions, such as the prefrontal, supplementary motor, primary motor, somatosensory and posterior parietal cortices, and the cerebellum. We found positive associations of PS and external LoC with painfulness ratings, and a negative correlation between PS and internal LoC. Despite our hypotheses, neither PS nor internal LoC were significant predictors of the BOLD-signal contrasts. Though future studies are needed to draw further conclusions, our results provide preliminary evidence of a potential neuronal imagination-perception overlap in pain.

The link between cutaneous allodynia and pain/sensitivity in teeth and gums during migraine episodes.

BACKGROUND: Migraine is one of the most common primary headaches worldwide, while toothache is the most common pain in the orofacial region. The association of migraine pain, and oral pain is unknown. This study aims to investigate the association between migraine and dental and gingival pain with the presence of allodynia. METHODS: A questionnaire comprising demographic data with the ID-Migraine (IDM) tool, an Allodynia Symptom Checklist (ASC), and inquiries about pain and sensitivity in the teeth and gums during migraine attacks was administered to the participants and 762 responded the survey. The study classified participants based on the ASC, and the relationship between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks was analyzed. The statistical analyses utilized Chi-square tests and the Fisher-Exact test. RESULTS: Among 762 migraine patients, 430 (56.44%) were classified as allodynia (+), while 332 (43.56%) were classified as allodynia (-) (p < 0.001). Additionally, 285 participants (37.5%) reported experiencing pain and sensitivity in the teeth and gums during migraine attacks, with a significant relationship observed between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks (p < 0.001). CONCLUSION: The findings of this study have important clinical implications. For migraine patients who are non-allodynic, the presence of pain and sensitivity in their teeth and gums during migraine attacks may indicate underlying dental diseases or the need for dental treatment especially root canal treatment. However, for allodynic patients, such symptoms may not necessarily indicate the presence of dental diseases or the need for dental treatment especially root canal treatment. These results underscore the significance of considering the presence of allodynia in the assessment and management of oral symptoms during migraine attacks.

The Experimental Pain Experienced in a Cold Pressor Task Is Influenced by Hemoglobin Levels in Young Adult Females.

INTRODUCTION: The intensity of pain perceived for the same noxious stimulus is different in different persons, depending on the biological, psychological, and social factors related to the individual. In clinical practice, it is important to know the factors influencing pain perception. The presence of anemia may affect pain perception. METHODS: This study was conducted on 73 female subjects of whom 25 were non-anemic, 24 had mild, and 24 had moderate anemia. Experimental pain was produced by cold pressor task (CPT). Pain response was evaluated in terms of cardiovascular reactivity (CVR - changes in blood pressure and heart rate), and pain sensitivity (PS - pain threshold, pain tolerance, and pain rating). RESULTS: Anemic subjects showed higher CVR to stress. The average increase in systolic blood pressure was 5.28 mm of Hg in non-anemic, compared to 3.25 in mildly anemic and 9.00 mm of Hg in moderately anemic subjects. The average increase in diastolic blood pressure was 2.24 mm of Hg in non-anemic, 2.5 in mildly anemic, and 4.83 mm of Hg in moderately anemic subjects. The average increase in heart rate was 2.88 beats per minute (bpm) in non-anemic, 4.83 in mildly anemic, and 7 bpm in moderately anemic subjects. Pain rating was higher in anemic subjects (average 7.21) compared to the non-anemic subjects (average 6.44). CONCLUSION: CPT-induced pain causes greater cardiovascular reactivity in anemic patients. The average pain rating is higher in anemic subjects.

Exploratory Study of Biomechanical Properties and Pain Sensitivity at Back-Shu Points.

OBJECTIVES: Hypersensitive acupoints in specific body areas are associated with corresponding internal or visceral disorders. Back-shu points are clinically significant for the diagnosis of visceral organ disease, according to the biomechanical characteristics of the acupoints. In this study, we assessed the biomechanical characteristics and pain sensitivities of five back-shu points linked to five visceral organs in healthy participants. METHODS: The study included 48 volunteer participants. A myotonometry was used to assess muscle tone and muscle stiffness at five back-shu points associated with visceral organs. Pressure was monitored using a microcontroller and a force sensor. Pain sensitivity was assessed in response to deep pressure pain produced by a constant force. RESULTS: Substantial differences in muscle tone and stiffness were observed at the five back-shu points; muscle tone was highest at BL15, whereas muscle tone and muscle stiffness were lowest at BL23. Moreover, pain sensitivity was significantly different among the acupoints; pain sensitivity was highest at BL23. There was a significant negative correlation between muscle tone and pain sensitivity. CONCLUSIONS: We found significant differences in muscle tone, muscle stiffness, and pain sensitivity among five back-shu points associated with visceral organs, which may be attributable to anatomical variations at each point. Our findings suggest that differences at back-shu points should be considered to ensure the accurate diagnosis of visceral disease.

Longitudinal associations between beta-endorphin, nonsuicidal self-injury and comorbid psychopathology.

Homeostasis models posit that nonsuicidal self-injury (NSSI) serves, in part, to upregulate the endogenous opioid system in order to compensate for an opioid deficiency. A few studies have demonstrated lower basal levels of beta-endorphin (BE), an endogenous opioid, in individuals with NSSI. However, longitudinal studies are missing. Hence, the present study aimed to investigate the longitudinal associations between NSSI, comorbid psychopathology (i.e., borderline personality disorder and depressive symptoms), pain sensitivity and basal BE levels in adolescents with NSSI. N = 53 adolescents with NSSI disorder undergoing specialized treatment participated in baseline and one-year follow-up assessments. BE was measured in plasma; pain sensitivity was assessed with a heat pain stimulation paradigm. Associations between BE and change in NSSI, borderline personality disorder and depressive symptoms as well as pain sensitivity were examined using negative binomial and linear regression analyses. We found that an increase in basal BE was significantly associated with a decrease in depressive symptoms. No associations between BE and NSSI, borderline personality disorder symptoms or pain sensitivity were observed. Our findings may confirm a role of plasma BE in the etiology of depressive symptoms but challenge current models of endogenous opioid homeostasis in NSSI.

Sex Differences in Pain Sensitivity in a Dutch Cohort: Cross-Sectional and Web-Based Multidimensional Study.

BACKGROUND: Sex is an important factor influencing the development and treatment of chronic pain, but the extent of its influence is still unclear. Other demographic factors as well as nonpharmacological interventions might influence pain sensitivity differently in men and women. OBJECTIVE: In this study, we aimed to investigate the influence of sex and other demographic, lifestyle, behavioral, clinical, and environmental factors on pain sensitivity in the Dutch population. Different films were used to investigate how they would impact pain sensitivity and what influence sex and other variables have on the effect of this simple intervention. METHODS: We performed a study consisting of 2 parts: (1) a cross-sectional research to investigate pain sensitivity differences between men and women and the influence of other demographic variables on the pain sensitivity in a Dutch cohort and (2) an internet intervention study to determine whether a short film could skew pain sensitivity. RESULTS: All respondents filled in a web-based demographic questionnaire and were randomized into 4 groups. The control group filled in the Pain Sensitivity Questionnaire without watching a preliminary film. A cross-sectional analysis was performed in the control group (n=1746). The other 3 groups watched short films: one group watched a film with scenes of nature (n=2650), another group watched a film on laughing people (n=2735), and the last group watched a film on physically painful events (n=2708). Immediately after the film viewing, participants were directed to the Pain Sensitivity Questionnaire to measure their pain sensitivity. The Pain Sensitivity Questionnaire score was stated as a mean per question on the numeric rating scale from 0-1. The cross-sectional study revealed no significant differences between men and women but showed male-female differences in the Pain Sensitivity Questionnaire when specific background factors were present. Watching a short film had a positive impact on the pain sensitivity of the respondents who had chronic pain, with a higher effect observed in female respondents. CONCLUSIONS: Scientists performing pain research need to account for factors that can influence the outcome of their study and be aware that these factors can be sex-dependent, and pain sensitivity should be analyzed accordingly. Even relatively small interventions such as watching a film can impact pain sensitivity, especially in respondents with current chronic pain. This effect can vary as well when different background factors are present. Our findings warrant further explorations of the possibilities that simple interventions bring for patients in personalized medicine. TRIAL REGISTRATION: Landelijk Trial Register NTR-new NL8182; https://onderzoekmetmensen.nl/en/trial/29537.

Pain Sensitivity Questionnaire: Cross-cultural adaptation and validation of the Greek version.

INTRODUCTION: The Pain Sensitivity Questionnaire (PSQ) was developed to assess general pain sensitivity. OBJECTIVE: This study aimed to validate the Greek version of PSQ. METHODS: The questionnaire was translated into Greek (PSQ-GR) and piloted in a small sample of patients with chronic pain (n = 35). A total of 146 chronic pain patients and healthy volunteers completed the PSQ-GR, the Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) and Central Sensitization Inventory (CSI). To evaluate the test-retest reliability, 36 volunteers completed the PSQ-GR twice over 7 ± 2 days. RESULTS: Internal consistency was excellent (Cronbach's alpha 0.90-0.96) for PSQ-total, PSQ-minor, and PSQ-moderate. The Intraclass Correlation Coefficient was estimated at 0.90-0.96 for PSQ-total, PSQ-minor and PSQ-moderate and the SEM was 0.59-0.90 for PSQ-total, PSQ-minor and PSQ-moderate approximately. The smallest detectable change was 0.48 for PSQ-total, 0.47 for PSQ-minor and 0.44 for PSQ-moderate. Positive and significant correlations were observed between PSQ-GR and HADS (r = 0.38, p < 0.01), PCS (r = 0.41, p < 0.01) and CSI (r = 0.30, p < 0.01). Statistically significant differences in PSQ-GR scores were identified between the healthy volunteers and the chronic pain patients. CONCLUSION: The PSQ-GR is a reliable and valid tool that can assess pain sensitivity in healthy individuals and chronic musculoskeletal pain patients.

Diminished vibration perception and greater pressure pain sensitivity are associated with worse knee osteoarthritis outcomes across sex and race.

OBJECTIVE: To examine associations of vibration sensitivity and pressure pain sensitivity with knee osteoarthritis (OA) outcomes across sex and race, which may relate to known sex and race disparities in clinical outcomes. DESIGN: Data were from the 2013-2015 visit of the Johnston County Osteoarthritis Project. Exposures were vibration perception threshold (VPT) measured at the bilateral medial femoral condyle (MFC) and first metatarsophalangeal joint (MTP), and pressure pain threshold (PPT) measured at the bilateral upper trapezius. Outcomes were knee pain severity and presence of knee symptoms, radiographic knee OA, and symptomatic knee OA in each knee. Cross-sectional associations of the exposures with the outcomes were examined using logistic regression models, overall and separately by sex and race. RESULTS: In the VPT and PPT analyses, 851 and 862 participants (mean age 71 years, 68% female, 33% Black, body mass index 31 kg/m2) and 1585 and 1660 knees were included, respectively. Higher VPT (lower vibration sensitivity) at the MFC and first MTP joint was associated with all outcomes. Lower PPT (greater pressure pain sensitivity) was associated with greater knee pain severity. Associations of VPT and PPT with all outcomes were similar among females and males and Black and White individuals. CONCLUSIONS: Diminished vibration perception and greater pressure pain sensitivity were cross-sectionally associated with worse knee OA outcomes. Despite differences in VPT and PPT among females and males and Black and White adults, associations with knee OA outcomes did not differ by sex or race, suggesting neurophysiological differences do not relate to established disparities.

Influence of psychological factors and pain sensitivity on the efficacy of opioid-free anesthesia: A randomized clinical trial.

OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).

Preoperative pain sensitivity and its correlation with postoperative acute and chronic pain: a systematic review and meta-analysis.

BACKGROUND: Preoperative pain sensitivity (PPS) can be associated with postsurgical pain. However, estimates of this association are scarce. Confirming this correlation is essential to identifying patients at high risk for severe postoperative pain and for developing analgesic strategy. This systematic review and meta-analysis summarises PPS and assessed its correlation with postoperative pain. METHODS: PubMed, Scopus, Cochrane Library, and PsycINFO were searched up to October 1, 2023, for studies reporting the association between PPS and postsurgical pain. Two authors abstracted estimates of the effect of each method independently. A random-effects model was used to combine data. Subgroup analyses were performed to investigate the effect of pain types and surgical procedures on outcomes. RESULTS: A total of 70 prospective observational studies were included. A meta-analysis of 50 studies was performed. Postoperative pain was negatively associated with pressure pain threshold (PPT; r=-0.15, 95% confidence interval [CI] -0.23 to -0.07]) and electrical pain threshold (EPT; r=-0.28, 95% CI -0.42 to -0.14), but positively correlated with temporal summation of pain (TSP; r=0.21, 95% CI 0.12-0.30) and Pain Sensitivity Questionnaire (PSQ; r=0.25, 95% CI 0.13-0.37). Subgroup analysis showed that only TSP was associated with acute and chronic postoperative pain, whereas PPT, EPT, and PSQ were only associated with acute pain. A multilevel (three-level) meta-analysis showed that PSQ was not associated with postoperative pain. CONCLUSIONS: Lower PPT and EPT, and higher TSP are associated with acute postoperative pain while only TSP is associated with chronic postoperative pain. Patients with abnormal preoperative pain sensitivity should be identified by clinicians to adopt early interventions for effective analgesia. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023465727).

Evaluation of the segmental distribution of pain sensitivity among patients with central sensitization associated with chronic subacromial pain syndrome: A cross-sectional study.

INTRODUCTION: Pain sensitivity is the main finding of central sensitization (CS) and can occur in patients with chronic shoulder pain. However, there is limited evidence concerning the distribution of pain sensitivity in shoulders, forearms, and legs in patients with CS associated with chronic shoulder pain. The present study aimed to determine the distribution of pain sensitivity in patients with CS associated with chronic subacromial pain syndrome (SPS). METHOD: This cross-sectional study included 58 patients with chronic SPS and CS (patient group) and 58 healthy participants (control group). The presence of CS was determined using the Central Sensitization Inventory (CSI). To determine the distribution of pain sensitivity, pressure pain threshold (PPT) measurements were performed from the shoulders, forearms, and legs. RESULTS: There was no significant difference between the two groups in terms of sociodemographic data (p > 0.05). The patient group had a significantly higher CSI score (p < 0.001) and lower PPTs in all regions (p < 0.05) than the control group. Unlike the control group, the patient group had lower PPTs on the affected side for the shoulder [mean difference (MD) 95% confidence interval (CI): 1.2 (-1.7 to -0.6)], forearm [MD 95% CI: 1.1 (-1.7 to -0.6)], and leg [MD 95% CI: 0.9 (-1.4 to -0.3)] compared with the contralateral side (p < 0.001). CONCLUSION: Pain sensitivity is more pronounced in the affected shoulder and the forearm and leg located on this side than in those on the contralateral side in patients with CS associated with chronic SPS.

The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model.

OBJECTIVE: Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene-related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP-25 through western blot analysis to gain insights into the mechanistic action of BoNT/A. METHODS: BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post-inflammation, and alterations in CGRP release were evaluated. Changes in SNAP-25 levels were determined using western blot analysis. RESULTS: Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP-25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A-treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release. CONCLUSION: Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.

Exploring the association of gender role expectations of pain and measures of pain sensitization in people with knee osteoarthritis: A cross-sectional study.

OBJECTIVES: First, we explored the association between Gender Role Expectations of Pain (GREP), and psychophysical measures of sensitization in people with knee osteoarthritis (OA). Second, we explored whether the association differed by level of GREP items (high vs low scores). DESIGN: We conducted secondary analyses of a cohort study. Those who were (i) age of ≥40, English or French speaking, ii) diagnosed with knee OA using American College of Rheumatology criteria and iii) consulting with an orthopedic surgeon were included. GREP items pertaining to pain sensitivity and pain endurance of the typical man or woman were rated by males and females respectively. Psychophysical tests consisted of pressure pain thresholds (PPTs), Temporal Summation (TS), and Conditioned Pain Modulation (CPM). Multiple linear regression models for males and females were run with GREP scores (independent variables) and psychophysical tests (dependent variables). Next models stratified on the median split of GREP scores were run. Models were adjusted for age, BMI, pain catastrophizing, anxio-depressive symptoms, and radiographic severity. RESULTS: 280 participants (57% females; age (SD): 63.9 (9.6) and BMI (SD): 31.3 (8.40)) were included. GREP pain sensitivity scores in males were associated with CPM values (ß: 95% CI: 0.09 (0.01 to 0.17)). Males with low GREP pain sensitivity or pain endurance had very small to small positive associations with PPT and CPM values. CONCLUSION: This first exploration of gendered pain sensitivity and pain endurance by males and females has small and clinically unimportant associations with measures of pain sensitization requiring further validation.

Impaired Carbohydrate Metabolism among Women with Chronic Low Back Pain and the Role of Dietary Carbohydrates: A Randomized Controlled Cross-Over Experiment.

Background: Impaired glucose regulation is suggested to be related to chronic low back pain (CLBP), although it is not clear how they interact with each other. Thus, the primary aim of this study was to investigate differences in postprandial glycemic responses (PPGRs) (the first sign of impaired glucose metabolism) to high- (sucrose) and low-glycemic index (GI) (isomaltulose) beverages in normoglycemic women with CLBP and healthy controls (HCs) and explore whether any group that showed greater PPGRs to high-GI beverage intake would benefit when the high-GI beverage was replaced with a low-GI beverage. Secondly, this study aimed to explore the association between PPGR and pain in patients with CLBP. Methods: This study was registered at clinicaltrials.org (NCT04459104) before the start of the study. In this study, 53 CLBP patients and 53 HCs were recruited. After 11-12 h of fasting, each participant randomly received isomaltulose or sucrose. Blood glucose levels were measured during the fasting state and 15, 30, 45, 60, 90, and 120 min after the beverage intake, and each participant underwent experimental pain measures. Results: Compared to the HCs, the CLBP group showed significantly higher PPGRs to sucrose (p < 0.021). Additionally, the CLBP group showed a significantly higher decrease in PPGR (p = 0.045) when comparing PPGR to sucrose with PPGR to isomaltulose. Correlation analysis revealed a positive association between self-reported pain sensitivity and PPGR to sucrose, while there was no association found between any experimental pain measures and glycemic responses. Conclusions: Overall, these findings suggest that normoglycemic CLBP patients might have a higher risk of developing impaired glucose tolerance than the HCs and might benefit more when high-GI foods are replaced with low-GI ones.

Testing Biological and Psychological Pathways of Emotion Regulation as a Primary Mechanism of Action in Yoga Interventions for Chronic Low Back Pain: Protocol for a Randomized Controlled Trial.

BACKGROUND: Interventions that promote adaptive emotion regulation (ER) skills reduce pain in patients with chronic pain; however, whether the effects of yoga practice on chronic low back pain (CLBP) are due to improvements in ER remains to be examined. OBJECTIVE: This study will test whether the effects of yoga on CLBP (improved pain severity and interference) are mediated by improved ER, the extent to which effects are related to specific aspects of ER, and the role of pain sensitization as a mediator or moderator of effects. In this study, pain sensitization will be assessed by quantitative sensory testing and gene expression profiles to examine whether pain sensitization moderates yoga's effects on pain or whether yoga and ER abilities reduce pain sensitization, leading to decreased pain severity and interference. METHODS: For this 2-arm parallel group blinded randomized controlled trial, we will enroll 204 adults with CLBP who will be randomized to receive the yoga (n=102) or a control stretching and strengthening (n=102) intervention, which are delivered via web-based synchronous biweekly 75-minute sessions over 12 weeks. Participants are encouraged to practice postures or exercises for 25 minutes on other days using accessible prerecorded practice videos that are sent to participants digitally. Participants will be assessed at 5 time points: baseline, midintervention (6 weeks), postintervention (12 weeks), and 3- and 6-month follow-ups. Assessments of ER, pain severity and interference, pain sensitivity including somatosensory and gene expression profiles, and physical strength and flexibility will be conducted at each visit. The fidelity of the interventions is assessed using a manualized checklist to evaluate recorded group sessions to ensure consistent instructor delivery. RESULTS: The primary outcome will be the mean change in pain severity as measured by the Brief Pain Inventory-Short Form at 12 weeks. The primary mechanism of action is ER measured by change in the Difficulties in Emotion Regulation Scale total score. Secondary outcomes include pain sensitivity, physical strength and flexibility, pain interference, and quality of life. A mediation path analysis and series of moderated mediation path analyses will be conducted to test the study hypotheses. As of January 2024, we have enrolled 138 participants. We expect the study to be completed by May 2025. CONCLUSIONS: The study will provide important data for evaluating whether improvements in ER are responsible for reduced pain perception and pain sensitivity as well as increased quality of life in the context of chronic pain. The study findings have important implications for determining the mechanism of action for yoga and possibly other mind-body interventions as nonpharmacological therapies for pain management. The results of the study will inform the content, delivery, and measures for intervention trials involving yoga as a modality for relieving pain and improving function. TRIAL REGISTRATION: ClinicalTrials.gov NCT04678297; https://clinicaltrials.gov/study/NCT04678297. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56016.

Pain sensitivity as a state marker and predictor for adolescent non-suicidal self-injury.

BACKGROUND: The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI. METHODS: N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses. RESULTS: We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction (p = 0.059). No associations between PS and BPD or depressive symptoms were observed. CONCLUSION: Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and positively influences pain sensitivity and work capacity.

The aim of the study was to investigate the effects of rat housing conditions-standard conditions, social isolation, environmental enrichment-and the subsequent reversal of these conditions on the vulnerability of the gastric mucosa to ulcerogenic stimuli, somatic pain sensitivity, and treadmill work capacity. Rats, aged 30 days, were placed in standard conditions (SC), social isolation (Is), and environmental enrichment (EE) for 4 weeks. Then half of each group underwent a reversal of housing conditions: SC rats were moved to Is, Is rats were placed in EE, EE rats were moved to Is, for 2 weeks. The other half served as a control with no change in their initial housing. Two weeks after the reversal, vulnerability of the gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, sc), somatic pain sensitivity (hot plate test), and work capacity (measured by the running distance on a treadmill) were assessed in control and reversed groups. Social isolation induced a proulcerogenic effect, increasing IM-induced gastric erosions, which was effectively reversed when rats were transferred to an environmental enrichment. Conversely, transferring rats from an environmental enrichment to social isolation exacerbated ulcerogenic action of IM. Somatic pain sensitivity and treadmill work capacity were also influenced by housing conditions, with environmental enrichment showing positive effects. The present findings show that social isolation of rats induces a proulcerogenic effect. Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and increases resilience to pain stimuli and treadmill work capacity.

Delayed-Onset Muscle Soreness Alters Mechanical Sensitivity, but Not Thermal Sensitivity or Pain Modulatory Function.

Introduction: Many clinical musculoskeletal pain conditions are characterized by chronic inflammation that sensitizes nociceptors. An unresolved issue is whether inflammation affects all nociceptors in a similar manner. Exercise-induced muscle damage (EIMD) has been proposed as a model for simulating clinical inflammatory pain in healthy samples. We sought to test the effect of EIMD on various painful stimuli (pressure and thermal), central pain processing (via the nociceptive flexion reflex) and endogenous pain modulation via conditioned pain modulation and exercise-induced hypoalgesia. Methods: Eighteen participants (9F, age: 24.6 ± 3.3) were recruited for repeated measures testing and each completed pain sensitivity testing prior to and 48 hours after an eccentric exercise protocol. The participants performed a minimum of 6 rounds of 10 eccentric knee extension exercises to induce muscle damage and localized inflammation in the right quadriceps. Force decrements, knee range-of-motion, and delayed onset muscle soreness (DOMS) were used to quantify EIMD. Results: There was a significant main effect of time for pressure pain (%diff; -58.9 ± 23.1; p = 0.02, ηp2 = 0.28) but no significant main effect was observed for limb (%diff; -15.5 ± 23.9; p = 0.53, ηp2 = 0.02). In contrast, there was a significant interaction between time and limb (p < 0.001, ηp2 = 0.47) whereby participants had lower pressure pain sensitivity in the right leg only after the damage protocol (%diff; -105.9 ± 29.2; p = 0.002). Discussion: Individuals with chronic inflammatory pain usually have an increased sensitivity to pressure, thermal, and electrical stimuli, however, our sample, following muscle damage to induce acute inflammation only had sensitivity to mechanical pain. Exercise induced inflammation may reflect a peripheral sensitivity localized to the damaged muscle rather than a global sensitivity like those with chronic pain display.