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BMJ Open Jun 2024An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism....
BACKGROUND
An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism. For individuals with cervicogenic headache (CeH), the characteristics of such profiles were never investigated. However, the individual nature of experiencing pain demands profiling within a multidimensional framework including psychosocial lifestyle characteristics. The objective of the current protocol is to assess the pain modulation profile, which includes psychosocial lifestyle characteristics among people with CeH.
METHODS AND ANALYSIS
A protocol is described to map pain modulation profiles in people with CeH. A cross-sectional non-randomised experimental design will be used to assess feasibility of mapping these profiles. The pain modulation profile is composed based on results on the Depression, Anxiety, Stress Scale, Pittsburgh Sleep Quality Index, Headache Impact Test and on responses to temporal summation of pain (pinprick), conditioned pain modulation and widespread hyperalgesia (mechanical pressure pain threshold and cuff algometry). Primary analyses will report results relating to outcomes on feasibility. Secondary analyses will involve an analysis of proportions (%) of the different psychosocial lifestyle profiles and pain profiles.
ETHICS AND DISSEMINATION
Ethical approval was granted by the Ethics Committee Research UZ/KU Leuven (Registration number B3222024001434) on 30 May 2024. Results will be published in peer-reviewed journals, at scientific conferences and, through press releases. Protocol V.3. protocol date: 3 June 2024.
Topics: Humans; Post-Traumatic Headache; Feasibility Studies; Cross-Sectional Studies; Pain Measurement; Adult; Pain Threshold; Male; Female; Life Style
PubMed: 38890144
DOI: 10.1136/bmjopen-2023-074743 -
Journal of Science and Medicine in Sport May 2024Explore if implementing an individualised Sub-Symptom Heart Rate Threshold (SSHeRT) rehabilitation program within 48 hours versus physical rest for 14 days affects...
A controlled early-exercise rehabilitation program commencing within 48 hours of a Sports-Related Concussion improves recovery in UK student-athletes: A prospective cohort study.
OBJECTIVES
Explore if implementing an individualised Sub-Symptom Heart Rate Threshold (SSHeRT) rehabilitation program within 48 hours versus physical rest for 14 days affects recovery following SRC in university-aged student-athletes.
DESIGN
Prospective, observational cohort study.
METHODS
Two UK university-aged student-athlete rugby union cohorts were compared (Physical Rest Group (PRG), n = 140, July 2019-March 2020 and Controlled Early-Exercise Group (CEG), n = 167, July 2021-April 2023). Both groups completed the test battery (Post-Concussion Symptom Scale (PCSS), Immediate Post-Concussion and Cognitive Test (ImPACT), Vestibular-Ocular Motor Screening Tool (VOMS)) during pre-season to provide a baseline and within 48 hours, at 4, 8, 14-days post-SRC and at Return to Play (RTP). The PRG (n = 42) physically rested for 14 days as per the nationwide community guidelines. The CEG (n = 52) followed the SSHeRT rehabilitation program. Individual change to baseline was used in all analyses.
RESULTS
The CEG performed better on ImPACT's verbal memory at 4 (PRG; -5.5 (-10.8-0.0), CEG; 1.0 (-2.0-10.5), p = 0.05) and 14 days (PRG; -2.0 (-10.0-3.0), CEG; 4.0 (-1.0-11.0), p = 0.05) and on the VOMS at 4 (PRG; 3.0 (0.0-12.0), CEG; 0.0 (0.0-5.0), p = 0.03, OR; 2.910) and 14-days post-SRC (PRG; 0.0 (0.0-1.0), CEG; 0.0 (0.0-0.0), OR; 5.914). Near point convergence was better at all time points for the CEG. The CEG was 26.7 % more likely to have RTP within 30 days, and 6.7 and 5.1 times more likely to have resumed non-contact and contact academic activities by 4 days.
CONCLUSIONS
SSHeRT is safe, can be used within 48 hours of a SRC and may hasten university-aged student-athletes recovery following an SRC.
PubMed: 38890020
DOI: 10.1016/j.jsams.2024.05.011 -
Physiological Reports Jun 2024Dynamic resistance exercise may produce reductions in pain locally at the exercising muscle and systemically at non-exercising sites. However, limited research has...
Dynamic resistance exercise may produce reductions in pain locally at the exercising muscle and systemically at non-exercising sites. However, limited research has examined these changes with multiple noxious stimuli. This study examined changes in heat pain threshold (HPT) and pressure pain threshold (PPT) on different musculature after an upper and lower body exercise to compare local and systemic effects. A crossover design with 28 participants (mean age: 21 ± 4 years, 21 female) completed three sessions. Visit one included baseline quantitative sensory testing and 5-repetition maximum (RM) testing for upper (shoulder press) and lower (leg extension) body. In subsequent sessions, participants performed upper or lower body exercises using an estimated 75% 1-RM with pre/post assessment of HPT and PPT at three sites: deltoid, quadriceps, and low back. A significant three-way interaction was observed for HPT (F (1.71, 3.80) = 2.19, p = 0.036, ηp = 0.12) with significant increases in HPT over the quadriceps (p = 0.043) after leg extension and over the deltoid (p = 0.02) after shoulder press. Significant systemic changes were not observed for HPT or PPT. Local but not systemic effects were demonstrated after an acute bout of exercise. Peripheral pain sensitivity may be more responsive to heat stimuli after resistance exercise.
Topics: Humans; Female; Pain Threshold; Male; Resistance Training; Young Adult; Adult; Muscle, Skeletal; Cross-Over Studies; Hot Temperature; Adolescent
PubMed: 38890005
DOI: 10.14814/phy2.16123 -
Neuropsychobiology Jun 2024The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated....
Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.
INTRODUCTION
The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms.
METHODS
We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined.
RESULTS
Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003).
CONCLUSION
This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.
PubMed: 38889691
DOI: 10.1159/000538971 -
Rheumatology (Oxford, England) Jun 2024Neuropathic-like pain, fatigue, cognitive difficulty, catastrophising, anxiety, sleep disturbance, depression, and widespread pain associate with a single factor in...
BACKGROUND AND AIMS
Neuropathic-like pain, fatigue, cognitive difficulty, catastrophising, anxiety, sleep disturbance, depression, and widespread pain associate with a single factor in people with knee pain. We report the Central Aspects of Pain questionnaire (CAP) to characterise this across painful musculoskeletal conditions.
METHODS
CAP was derived from the 8 item CAP-Knee questionnaire, and completed by participants with joint pain in the Investigating Musculoskeletal Health and Wellbeing survey. Subgroups had osteoarthritis, back pain or fibromyalgia. Acceptability was evaluated by feedback and data missingness. Correlation coefficients informed widespread pain scoring threshold in relation to the other items, and evaluated associations with pain. Factor analysis assessed CAP structure. Intraclass Correlation Coefficient (ICC) between paper and electronic administration assessed reliability. Friedman test assessed score stability over 4 years in people reporting knee osteoarthritis.
RESULTS
Data were from 3579 participants (58% female, median age; 71 years), including subgroups with osteoarthritis (n = 1158), back pain (n = 1292) or fibromyalgia (n = 177). Across the 3 subgroups, ≥10/26 painful sites on the manikin scored widespread pain. Reliability was high (ICC= 0.89 (95% CI: 0.84-0.92)) and CAP scores fit to 1 and 2 factor model, with a total CAP score that was associated with pain severity and quality (r = 0.50-0.72). In people with knee pain, CAP scores were stable over 4 years at the group level, but displayed significant temporal heterogeneity within individual participants.
CONCLUSIONS
Central Aspects of Pain is reliably measured by the CAP questionnaire across a range of painful musculoskeletal conditions, and is a changeable state.
PubMed: 38889286
DOI: 10.1093/rheumatology/keae342 -
Pain Jun 2024Chronic pain in inflammatory arthritis (IA) reflects a complex interplay between active disease in a peripheral joint and central pronociceptive mechanisms. Because...
Chronic pain in inflammatory arthritis (IA) reflects a complex interplay between active disease in a peripheral joint and central pronociceptive mechanisms. Because intra-articular lidocaine may be used to abolish joint-specific peripheral input to the central nervous system, we aimed to validate its use as a clinical tool to identify those patients with IA whose pain likely incorporates centrally mediated mechanisms. We began by investigating whether there was a placebo response of intra-articular injection in patients with IA 1:1 randomised to receive intra-articular lidocaine or control (0.9% saline). After, in a larger patient cohort not randomized to placebo vs lidocaine groups, we tested whether patients with IA could be stratified into 2 cohorts based on their response to intra-articular lidocaine according to markers of centrally mediated pain. To this end, we evaluated postlidocaine pain numerical rating scale (NRS) scores alongside baseline painDETECT, fibromyalgia criteria fulfillment, and quantitative sensory testing outcomes. Numerical rating scale scores were collected at baseline and 3-, 5-, and 10-minutes postinjection. Firstly, the placebo effect of intra-articular injection was low: compared to baseline, the mean pain NRS score 5-minutes postinjection was reduced by 3.5 points in the lidocaine group vs 1.2 points in the control group. Secondly, postlidocaine NRS scores were significantly higher in those with a high (>18) baseline painDETECT score, fibromyalgia, and low-pressure pain threshold at the trapezius (P = 0.002, P = 0.001, P = 0.005, respectively). Persistent high pain after intra-articular lidocaine injection could be used as an indicator of pronociceptive mechanisms that are centrally mediated, informing centrally targeted analgesic strategies.
PubMed: 38888846
DOI: 10.1097/j.pain.0000000000003291 -
The role of spinal neurons targeted by corticospinal neurons in central poststroke neuropathic pain.CNS Neuroscience & Therapeutics Jun 2024Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood.
BACKGROUND
Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood.
METHODS
By lesioning the lateral thalamic nuclei, we first established a CPSP model that exhibits mechanical and thermal hypersensitivity. Innocuous mechanical stimuli following the thalamic lesion evoked robust neural activation in somatosensory corticospinal neurons (CSNs), as well as in the deep dorsal horn, where low threshold mechanosensory afferents terminate. In this study, we used viral-based mapping and intersectional functional manipulations to decipher the role of somatosensory CSNs and their spinal targets in the CPSP pathophysiology.
RESULTS
We first mapped the post-synaptic spinal targets of lumbar innervating CSNs using an anterograde trans-synaptic AAV1-based strategy and showed these spinal interneurons were activated by innocuous tactile stimuli post-thalamic lesion. Functionally, tetanus toxin-based chronic inactivation of spinal neurons targeted by CSNs prevented the development of CPSP. Consistently, transient chemogenetic silencing of these neurons alleviated established mechanical pain hypersensitivity and innocuous tactile stimuli evoked aversion linked to the CPSP. In contrast, chemogenetic activation of these neurons was insufficient to induce robust mechanical allodynia typically observed in the CPSP.
CONCLUSION
The CSNs and their spinal targets are required but insufficient for the establishment of CPSP hypersensitivity. Our study provided novel insights into the neural mechanisms underlying CPSP and potential therapeutic interventions to treat refractory central neuropathic pain conditions.
Topics: Animals; Neuralgia; Pyramidal Tracts; Male; Stroke; Neurons; Hyperalgesia; Rats, Sprague-Dawley; Rats; Disease Models, Animal; Spinal Cord
PubMed: 38887838
DOI: 10.1111/cns.14813 -
Molecular Brain Jun 2024Areca nut, the seed of Areca catechu L., is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. The major effective...
Areca nut, the seed of Areca catechu L., is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. The major effective constituent of A. catechu, arecoline, has been reported to affect the central nervous system. Less is known if it may affect pain and its related emotional responses. In this study, we found that oral application of arecoline alleviated the inflammatory pain and its induced anxiolytic and anti-depressive-like behavior. Arecoline also increased the mechanical nociceptive threshold and alleviated depression-like behavior in naïve mice. In the anterior cingulate cortex (ACC), which acts as a hinge of nociception and its related anxiety and depression, by using the multi-electrode field potential recording and whole-cell patch-clamp recording, we found that the evoked postsynaptic transmission in the ACC of adult mice has been inhibited by the application of arecoline. The muscarinic receptor is the major receptor of the arecoline in the ACC. Our results suggest that arecoline alleviates pain, anxiety, and depression-like behavior in both physiological and pathological conditions, and this new mechanism may help to treat patients with chronic pain and its related anxiety and disorder in the future.
Topics: Animals; Synaptic Transmission; Anxiety; Arecoline; Male; Depression; Behavior, Animal; Nociception; Mice, Inbred C57BL; Gyrus Cinguli; Mice; Cerebral Cortex
PubMed: 38886822
DOI: 10.1186/s13041-024-01106-5 -
Anesthesia and Analgesia Jul 2024Peripheral nerve stimulation with a train-of-four (TOF) pattern can be used intraoperatively to evaluate the depth of neuromuscular block and confirm recovery from... (Comparative Study)
Comparative Study
BACKGROUND
Peripheral nerve stimulation with a train-of-four (TOF) pattern can be used intraoperatively to evaluate the depth of neuromuscular block and confirm recovery from neuromuscular blocking agents (NMBAs). Quantitative monitoring can be challenging in infants and children due to patient size, equipment technology, and limited access to monitoring sites. Although the adductor pollicis muscle is the preferred site of monitoring, the foot is an alternative when the hands are unavailable. However, there is little information on comparative evoked neuromuscular responses at those 2 sites.
METHODS
Pediatric patients undergoing inpatient surgery requiring NMBA administration were studied after informed consent. Electromyographic (EMG) monitoring was performed simultaneously in each participant at the hand (ulnar nerve, adductor pollicis muscle) and the foot (posterior tibial nerve, flexor hallucis brevis muscle).
RESULTS
Fifty patients with a mean age of 3.0 ± standard deviation (SD) 2.9 years were studied. The baseline first twitch amplitude (T1) of TOF at the foot (12.46 mV) was 4.47 mV higher than at the hand (P <.0001). The baseline TOF ratio (TOFR) before NMBA administration and the maximum TOFR after antagonism with sugammadex were not different at the 2 sites. The onset time until the T1 decreased to 10% or 5% of the baseline value (T1) was delayed by approximately 90 seconds (both P =.014) at the foot compared with the hand. The TOFR at the foot recovered (TOFR ≥0.9) 191 seconds later than when this threshold was achieved at the hand (P =.017). After antagonism, T1 did not return to its baseline value, a typical finding with EMG monitoring, but the fractional recovery (maximum T1 at recovery divided by the baseline T1) at the hand and foot was not different, 0.81 and 0.77, respectively (P =.68). The final TOFR achieved at recovery was approximately 100% and was not different between the 2 sites.
CONCLUSIONS
Although this study in young children demonstrated the feasibility of TOF monitoring, interpretation of the depth of neuromuscular block needs to consider the delayed onset and the delayed recovery of TOFR at the foot compared to the hand. The delay in achieving these end points when monitoring the foot may impact the timing of tracheal intubation and assessment of adequate recovery of neuromuscular block to allow tracheal extubation (ie, TOFR ≥0.9).
Topics: Humans; Male; Female; Electromyography; Prospective Studies; Child, Preschool; Muscle, Skeletal; Child; Neuromuscular Blockade; Infant; Foot; Electric Stimulation; Ulnar Nerve; Hand; Neuromuscular Blocking Agents; Neuromuscular Monitoring; Tibial Nerve
PubMed: 38885397
DOI: 10.1213/ANE.0000000000006926 -
Cureus May 2024Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints,...
BACKGROUND
Tenosynovial giant cell tumor (TGCT) is a monoarticular fibrohistiocytic benign or locally aggressive soft tissue tumor that originates from the synovium of joints, bursae, and tendon sheaths. It has an inflammatory neoplastic nature, with a clinical presentation ranging from pain, swelling, stiffness, and limited range of movement to joint instability and blockage. Its uncommon incidence leads to a poorly understood pathogenesis. Localized forms of TGCT (LTGCT) can cause significant morbidity, interfere with daily patient activities, and decrease the patient's quality of life in challenging cases. This study aimed to investigate the immunohistochemical expression of PPARγ (peroxisome proliferator-activated receptor gamma) and P53 in LTGCT to understand the disease better and offer potential therapeutic targets.
METHODS
The study is cross-sectional, in which 27 LTGCT cases were collected from the Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Solitary and multiple LTGCT cases retrieved between January 2018 and December 2022 were included, and immunohistochemically stained with anti-PPARγ and P53 antibodies. The TGCT samples were excluded if they were insufficient for sectioning, processing, and interpretation, over-fixed, had process artifacts, or were of the diffuse TGCT type. Scoring of stain expression was performed by ImageJ (National Institutes of Health, Bethesda, MD) analysis using the threshold method and was expressed in percent area/high power field. Clinicopathological correlations were analyzed.
RESULTS
All the 27 collected LTGCT cases were located in the small joints of patients' hands. Cases with solitary LGTCTs constituted 55.6% (n = 15), while 44.4% (n = 12) had multiple LTGCTs related to one affected site/case (e.g., multiple tumors in one finger). PPARγ was expressed in the cytoplasm of mononuclear and multinucleated tumor cells and foamy histiocytes, while P53 expression was mainly in mononuclear cells' nuclei. PPARγ significantly correlated with P53 expression (r = 0.9 and P = 0.000). PPARγ (r = 0.4 and P = 0.02) and P53 (r = 0.5 and P = 0.01) were positively correlated with tumor size. Only P53 expression was positively correlated with tumor multiplicity (r = 0.4 and P = 0.03). Using the receiver operating characteristic curve test, the P53 cutoff score detecting the multiplicity of TGCTs was ≥20.5%, with a 75% sensitivity and 80% specificity.
CONCLUSION
PPARγ and P53 have a significant role in LTGCT growth, while P53 plays a role in tumor multiplicity. They can be possible targets in LTGCTs unfit for excision.
PubMed: 38882990
DOI: 10.7759/cureus.60377