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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 -
ACS Omega Jun 2024This study aimed to develop a delivery system for the dried aqueous extract of leaves (RCE) that could improve the neuroprotective potential of RCE by improving the...
This study aimed to develop a delivery system for the dried aqueous extract of leaves (RCE) that could improve the neuroprotective potential of RCE by improving the bioavailability of the chief chemical constituent rubiadin. Rubiadin, an anthraquinone chemically, is a biomarker phytoconstituent of RCE. Rubiadin is reported to have strong antioxidant and neuroprotective activity but demonstrates poor bioavailability. In order to resolve the problem related to bioavailability, RCE and phospholipids were reacted in disparate ratios of 1:1, 1:2, and 1:3 to prepare phytosome formulations PC1, PC2, and PC3, respectively. The formulation PC2 showed particle size of 289.1 ± 0.21 nm, ζ potential of -6.92 ± 0.10 mV, entrapment efficiency of 72.12%, and release of rubiadin of 89.42% at pH 7.4 for a period up to 48 h. The oral bioavailability and neuroprotective potential of PC2 and RCE were assessed to evaluate the benefit of PC2 formulation over the crude extract RCE. Formulation PC2 showed a relative bioavailability of 134.14% with a higher neuroprotective potential and significantly ( < 0.05) augmented the nociceptive threshold against neuropathic pain induced by partial sciatic nerve ligation method. Antioxidant enzyme levels and histopathological studies of the sciatic nerves in various treatment groups significantly divulged that PC2 has enough potential to reverse the damaged nerves into a normal state. Finally, it was concluded that encapsulated RCE as a phytosome is a potential carrier system for enhancing the delivery of RCE for the efficient treatment of neuropathic pain.
PubMed: 38882167
DOI: 10.1021/acsomega.4c03774 -
Journal of Orthopaedic Surgery and... Jun 2024This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC)...
BACKGROUND
This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models.
METHODS
Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated.
RESULTS
The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten-eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups.
CONCLUSIONS
The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.
Topics: DNA Methylation; Animals; Osteoarthritis, Hip; Disease Models, Animal; Male; Rats; Iodoacetic Acid; Synovial Membrane; Leukocytes, Mononuclear; Rats, Sprague-Dawley; DNA Methyltransferase 3A; Pain Threshold
PubMed: 38880910
DOI: 10.1186/s13018-024-04847-0 -
Osteoarthritis and Cartilage Jun 2024To examine associations of vibration sensitivity and pressure pain sensitivity with knee osteoarthritis (OA) outcomes across sex and race, which may relate to known sex...
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/m) 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.
PubMed: 38880428
DOI: 10.1016/j.joca.2024.06.005 -
British Journal of Anaesthesia Jun 2024Preoperative pain sensitivity (PPS) can be associated with postsurgical pain. However, estimates of this association are scarce. Confirming this correlation is essential... (Review)
Review
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).
PubMed: 38879440
DOI: 10.1016/j.bja.2024.05.010 -
Journal of Bodywork and Movement... Jul 2024This study aimed to investigate the effect of sex on regional and widespread pain sensitivity following acute bouts of stretching and to investigate the acute effect of...
INTRODUCTION
This study aimed to investigate the effect of sex on regional and widespread pain sensitivity following acute bouts of stretching and to investigate the acute effect of stretching on regional and widespread pain sensitivity following stretching.
METHODS
73 healthy adults (36 females; mean age 25.6 ± 6.7 years) with an age range from 19 to 62 years were recruited for this experimental study. Regional and distant pain pressure pain thresholds, passive knee extension range of motion and passive resistive torque were measured before and 30 s after four bouts of 30-s static muscle stretching of the knee flexors with 20-s rest between bouts.
RESULTS
No significant sex differences were found for pressure pain thresholds (p > 0.132), range of motion (p = 0.446) or passive resistive torque (p = 0.559) between pre-stretch and post-stretch measures. There were significant increases in pressure pain thresholds (p = 0.010), range of motion (p = 0.001) and passive resistive torque (p = 0.007) between pre-stretch and post-stretch measures.
CONCLUSION
Muscle stretching significantly decreased regional and widespread pain sensitivity, indicating that central pain-modulating mechanisms are engaged during muscle stretching, resulting in stretch-induced hypoalgesia. Moreover, the results showed that the effect of stretching on regional and widespread pain sensitivity is not sex-specific.
Topics: Humans; Adult; Male; Female; Pain Threshold; Muscle Stretching Exercises; Range of Motion, Articular; Young Adult; Sex Factors; Middle Aged; Torque; Muscle, Skeletal; Knee Joint
PubMed: 38876646
DOI: 10.1016/j.jbmt.2024.02.003