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Pflugers Archiv : European Journal of... Oct 2023To advance evidence-based practice and targeted treatments of low back pain (LBP), a better pathophysiological understanding and reliable outcome measures are required....
To advance evidence-based practice and targeted treatments of low back pain (LBP), a better pathophysiological understanding and reliable outcome measures are required. The processing of nociceptive information from deeper somatic structures (e.g., muscle, fascia) might play an essential role in the pathophysiology of LBP. In this study, we measured the intra- and inter-session reliability of electrical detection and pain thresholds of cutaneous and muscle primary afferents of the lower back. Twenty healthy participants attended two study visits separated by 27.7 ± 1.7 days. To determine the location-specific electrical detection threshold (EDT) and pain threshold (EPT), needle electrodes were inserted in the epidermal layer over, and in the lumbar erector spinae muscle. Additionally, established quantitative sensory testing (QST) parameters were assessed. Reliability was determined by differences between measurements, intraclass correlation coefficients (ICC), Bland-Altman plots, and standard error of measurement (SEM). Correspondence between QST parameters and electrical thresholds was assessed using Pearson's correlation. Except for cutaneous EPT, no significant (p ≤ 0.05) intra- and inter-session differences were observed. Excellent intra-session reliability was shown for cutaneous and intramuscular electrical stimulations and all QST parameters (ICC: 0.76-0.93). Inter-session reliabilities were good (ICC: 0.74-0.75) except for electrical stimulations (ICC: 0.08-0.36). Limits of agreement and SEM were higher for inter-session than intra-session. A medium to strong relationship was found between electrical and mechanical/pressure pain thresholds. In conclusion, cutaneous and intramuscular electrical stimulation will potentially close an important diagnostic gap regarding the selective examination of deep tissue afferents and provide location-specific information for the excitability of non-nociceptive and nociceptive afferents.
Topics: Humans; Pain Threshold; Reproducibility of Results; Muscles; Low Back Pain; Electric Stimulation
PubMed: 37624386
DOI: 10.1007/s00424-023-02851-7 -
Brain Research Jul 2023Bone cancer pain (BCP) remains a clinical challenge due to the limited and side effects of therapeutic methods. Folic acid has been known as an FDA approved dietary...
BACKGROUND
Bone cancer pain (BCP) remains a clinical challenge due to the limited and side effects of therapeutic methods. Folic acid has been known as an FDA approved dietary supplement and proved to have an analgesic effect in neuropathic pain. Here we investigate the role and mechanism of folic acid in bone cancer pain of a rat model.
METHODS
Walker 256 tumor cells were inoculated into the left tibia of rats to induce bone cancer pain model. Pain reflex were assessed by paw withdrawal threshold (PWT) response to Von Frey filaments and paw withdrawal latency (PWL) response to thermal stimulation. Folic acid was injected intraperitoneally to evaluate its analgesic effect in rats with bone cancer pain. Western blotting and qPCR were used to determine P2X2/3 receptor protein and mRNA levels in ipsilateral L4-6 dorsal root ganglion (DRG) and spinal dorsal horn (SDH).
RESULTS
The PWT and PWL of rats with bone cancer pain were obviously decreased compared to the naïve and sham rats. Interestingly, continuous folic acid treatment significantly increased the PWT and PWL of rats with bone cancer pain. P2X2 and P2X3 receptors were clearly upregulated at both mRNA and protein expression in L4-6 DRG and SDH of rats with bone cancer pain. P2X2 and P2X3 receptors were mainly localized with CGRP (calcitonin gene-related peptide) or IB4 (isolectin B4) positive neurons in L4-6 DRG of rats with bone cancer pain. Notably, continuous folic acid treatment significantly reduced the expression of P2X2 and P2X3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Finally, intrathecal injection of A317491 (a selective antagonist of P2X2/3 receptors) markedly elevated the PWT and PWL of rats with bone cancer pain.
CONCLUSION
These results suggest that folic acid has an effective antinociceptive effect on bone cancer pain, which is mediated by downregulating P2X2/3 receptors in L4-6 DRG and SDH of rats with bone cancer pain. Folic acid may be a novel therapeutic strategy in cancer patients for pain relief.
Topics: Rats; Animals; Cancer Pain; Rats, Sprague-Dawley; Folic Acid; Neuralgia; Bone Neoplasms; Analgesics; RNA, Messenger; Ganglia, Spinal; Hyperalgesia
PubMed: 37164174
DOI: 10.1016/j.brainres.2023.148405 -
Journal of Orthopaedic Surgery and... Aug 2023Neuropathic pain (NP) is the most prevalent form of chronic pain resulting from nerve damage or injury. Despite the widespread use of Duhuo Jisheng decoction (DHJSD) in...
BACKGROUND
Neuropathic pain (NP) is the most prevalent form of chronic pain resulting from nerve damage or injury. Despite the widespread use of Duhuo Jisheng decoction (DHJSD) in traditional Chinese medicine (TCM) to treat chronic pain, the mechanism underlying its analgesic action remains unclear.
METHODS
Using network pharmacology, we obtained DHJSD and NP-related target information from public databases to construct protein-protein interactions (PPI) and compound-target networks based on common target genes. These networks were further analyzed using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). The interaction between molecules was verified through molecular docking using AutoDock Tools software. Additionally, we treated a chronic constriction injury (CCI) rat model with DHJSD and determined the mechanical withdrawal threshold (MWT). We used an enzyme-linked immunosorbent assay kit to determine the levels of inflammatory cytokines. Furthermore, qRT-PCR was employed to analyze ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA expression, and immunofluorescence was used to evaluate changes in microglia.
RESULTS
Our screening of compounds and targets identified 252 potential targets of DHJSD associated with NP. PPI analysis, along with GO and KEGG analyses, revealed that the potential mechanism of DHJSD in NP treatment may be related to inflammatory reactions, the IL-17 signaling pathway, MAP kinase activity, and endocrine activity. Based on molecular docking, the core target showed significant affinity for DHJSD's active components. Moreover, DHJSD treatment repaired the CCI-induced inflammatory reaction in the spinal cord while regulating the expression of ACHE, NOS2, MAPK3, PTGS2, AKT1, and PPARG mRNA. Immunofluorescence results indicated that the active components of DHJSD may regulate microglial M1 polarization to improve neuroinflammation, PPARG may have been involved in the process.
CONCLUSION
The multi-component, multi-target, and multi-pathway actions of DHJSD provide new insights into its therapeutic mechanism in NP.
Topics: Animals; Rats; Neuroinflammatory Diseases; Microglia; Chronic Pain; Cyclooxygenase 2; Molecular Docking Simulation; Network Pharmacology; PPAR gamma; Neuralgia; Inflammation
PubMed: 37635236
DOI: 10.1186/s13018-023-04121-9 -
Journal of Back and Musculoskeletal... 2024Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed... (Review)
Review
BACKGROUND
Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed to relate to central sensitization in humans, that is, Human Assumed Central Sensitization (HACS). The aims of this systematic review were to identify non-invasive objective markers of HACS and the instruments to assess these markers in patients with fibromyalgia (FM).
METHODS
A systematic review was conducted with the following inclusion criteria: (1) adults, (2) diagnosed with FM, and (3) markers and instruments for HACS had to be non-invasive. Data were subsequently extracted, and studies were assessed for risk of bias using the quality assessment tools developed by the National Institute of Health.
RESULTS
78 studies (n= 5234 participants) were included and the findings were categorized in markers identified to assess peripheral and central manifestations of HACS. The identified markers for peripheral manifestations of HACS, with at least moderate evidence, were pain after-sensation decline rates, mechanical pain thresholds, pressure pain threshold, sound 'pressure' pain threshold, cutaneous silent period, slowly repeated evoked pain sensitization and nociceptive flexion reflex threshold. The identified markers for central manifestations of HACS were efficacy of conditioned pain modulation with pressure pain conditioning and brain perfusion analysis. Instruments to assess these markers are: pin-prick stimulators, cuff-algometry, repetitive pressure stimulation using a pressure algometer, sound, electrodes and neuroimaging techniques.
CONCLUSIONS
This review provides an overview of non-invasive markers and instruments for the assessment of HACS in patients with FM. Implementing these findings into clinical settings may help to identify HACS in patients with FM.
Topics: Fibromyalgia; Humans; Central Nervous System Sensitization; Pain Threshold; Biomarkers; Pain Measurement
PubMed: 38073369
DOI: 10.3233/BMR-220430 -
International Journal of Oral Science Jan 2024Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed...
Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.
Topics: Humans; Bone Remodeling; Cell Differentiation; Osteogenesis; Semaphorin-3A; Trigeminal Ganglion
PubMed: 38238300
DOI: 10.1038/s41368-023-00269-6 -
Cureus Apr 2024Temporomandibular disorders (TMDs) represent a multifactorial condition involving a multitude of symptoms of the temporomandibular joint that emanates a series of...
BACKGROUND
Temporomandibular disorders (TMDs) represent a multifactorial condition involving a multitude of symptoms of the temporomandibular joint that emanates a series of distress. Understanding the relationship between these lifestyle factors and pain perception in TMD patients is essential for optimizing their management and care. This study delves into the intricate interplay between sleep, caffeine consumption, body mass index (BMI), and the potential effect on pressure pain threshold (PPT) values among individuals with TMDs.
MATERIALS AND METHODS
This is an observational study. Data were collected from a convenient sample of female patients at a single center in Riyadh city, between the ages of 20 and 50 years. The variables collected were based on an operator-designed questionnaire, the symptom questionnaire, and the Diagnostic Criteria for Temporomandibular Joint Disorders (DC/TMD).
RESULTS
A total of 139 participants were included in the study, appraising the occurrence of TMD and pain as per reports of caffeine intake and sleep duration. The observed outcomes indicate that the amount of sleep has a significant effect on the PPT values in TMD patients. This study highlights the substantial impact of sleep duration on lowering PPT values in individuals with TMDs. The findings highlight the importance of considering sleep duration and caffeine intake in the comprehensive management of TMD patients. There was no effect of BMI on this particular sample.
CONCLUSION
This study shows a positive correlation between sleep and pain and TMD, caffeine, and pain. A deeper understanding of these relationships could pave the way for more effective pain management strategies and personalized treatment approaches tailored to the unique needs of TMD patients. BMI had no effect.
PubMed: 38711687
DOI: 10.7759/cureus.57703 -
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 -
Clinical Rehabilitation Aug 2023To investigate the effects of multidirectional elastic tape on pain and function in individuals with lateral elbow tendinopathy. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the effects of multidirectional elastic tape on pain and function in individuals with lateral elbow tendinopathy.
STUDY DESIGN
Randomised crossover trial.
SETTING
Biomechanics laboratory.
SUBJECTS
27 participants (11 females, mean (SD) age: 48.6 (11.9) years) with clinically diagnosed lateral elbow tendinopathy of at least six weeks' duration.
INTERVENTIONS
Tensioned multidirectional elastic tape applied over the wrist, compared to control tape (untensioned), and no tape conditions.
MAIN MEASURES
Pain-free grip strength and pressure pain threshold were recorded at three timepoints for each condition: baseline, post-application, and following an exercise circuit. Change scores were calculated as the post-application or post-exercise value minus baseline. Repeated-measure analyses of variance were used to examine differences between conditions.
RESULTS
There were no statistically significant differences in pain-free grip strength between conditions (flexed position: F = 0.02, = 0.98; extended position: F = 2.26, = 0.12) or across timepoints (post-application vs post-exercise) (flexed position: F = 0.94, = 0.34; extended position: F = 0.79, = 0.38). Seven participants (26%) increased pain-free grip strength above the minimal detectable change following application of multidirectional elastic tape. There were no statistically significant differences in pressure pain threshold between conditions (affected lateral epicondyle: F = 0.54, = 0.54) or across timepoints (affected lateral epicondyle: F = 0.94, = 0.34).
CONCLUSION
Tensioned multidirectional elastic tape may not immediately improve pain-free grip strength or pressure pain threshold in our lateral elbow tendinopathy population; however, individual variation may exist.
Topics: Female; Humans; Middle Aged; Elbow Tendinopathy; Cross-Over Studies; Tennis Elbow; Pain; Elbow; Musculoskeletal Diseases; Hand Strength
PubMed: 36727206
DOI: 10.1177/02692155231152817 -
Cell Reports Methods Dec 2023Pain in rodents is often inferred from their withdrawal from noxious stimulation. Threshold stimulus intensity or response latency is used to quantify pain sensitivity....
Pain in rodents is often inferred from their withdrawal from noxious stimulation. Threshold stimulus intensity or response latency is used to quantify pain sensitivity. This usually involves applying stimuli by hand and measuring responses by eye, which limits reproducibility and throughput. We describe a device that standardizes and automates pain testing by providing computer-controlled aiming, stimulation, and response measurement. Optogenetic and thermal stimuli are applied using blue and infrared light, respectively. Precise mechanical stimulation is also demonstrated. Reflectance of red light is used to measure paw withdrawal with millisecond precision. We show that consistent stimulus delivery is crucial for resolving stimulus-dependent variations in withdrawal and for testing with sustained stimuli. Moreover, substage video reveals "spontaneous" behaviors for consideration alongside withdrawal metrics to better assess the pain experience. The entire process was automated using machine learning. RAMalgo (reproducible automated multimodal algometry) improves the standardization, comprehensiveness, and throughput of preclinical pain testing.
Topics: Mice; Animals; Pain Measurement; Reproducibility of Results; Pain; Pain Threshold; Behavior, Animal
PubMed: 37992707
DOI: 10.1016/j.crmeth.2023.100650 -
Pain Research & Management 2023Chronic pelvic inflammatory disease (CPID) is a clinically common gynecological disease. Patients experience chronic pelvic pain and often accompany with emotional...
BACKGROUND
Chronic pelvic inflammatory disease (CPID) is a clinically common gynecological disease. Patients experience chronic pelvic pain and often accompany with emotional dysfunction. However, the impact and correlation of anxiety and depression on pain sensitization is not completely known.
OBJECTIVE
To explore the differences and correlations among anxiety, depression, and pressure pain threshold (PPT) of acupoints in patients with CPID.
METHODS
One hundred and forty-seven patients with CPID were recruited. The Visual Analog Scale (VAS) and short-form McGill Pain Questionnaire (SF-MPQ) were used to assess pain. Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to evaluate the emotional state of patients. The PPT of acupoints was collected using an electronic Von Frey by two licensed acupuncturists.
RESULTS
The CPID patients were divided into anxiety-depression group (group A) or nonanxiety-depression group (group B), according to the SAS and SDS scores. Finally, there were 73 patients in group A and 74 patients in group B. Group A had significantly higher SAS, SDS, VAS, and SF-MPQ scores than group B ( < 0.05). In addition, significant differences were observed in the PPTs of ST28 (R), ST29 (R), SP10 (R), SP9 (R), SP9 (L), ST36 (R), and LR3 (L) between the two groups ( < 0.05). No considerable differences in PPTs at the other acupoints were observed between the two groups. SAS scores showed a positive correlation with PPTs of ST29 (R), SP10 (R), SP9 (L), ST36 (R), and LR3 (L). No remarkable correlation was observed between the SDS scores and PPTs.
CONCLUSION
Anxiety and depression can affect the PPT of some acupoints in CPID patients, which may provide a reference for acupoint selection for acupuncture treatment of CPID with emotional disorders. This trial is registered with ChiCTR2100052632.
Topics: Female; Humans; Depression; Pain Threshold; Acupuncture Points; Pelvic Inflammatory Disease; Anxiety; Chronic Pain
PubMed: 38033371
DOI: 10.1155/2023/3315090