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The Journal of Headache and Pain Mar 2024Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK)...
BACKGROUND
Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM.
METHODS
Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention.
RESULTS
Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1β, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway.
CONCLUSIONS
AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.
Topics: Mice; Animals; Nitroglycerin; Microglia; AMP-Activated Protein Kinases; NF-kappa B; Calcitonin Gene-Related Peptide; Central Nervous System Sensitization; Neurogenic Inflammation; Pain; Migraine Disorders
PubMed: 38454376
DOI: 10.1186/s10194-024-01739-w -
British Journal of Sports Medicine Jul 2023The primary aim was to investigate the effectiveness of adding more resistance exercise to usual care on pain mechanisms (including temporal summation, conditioned pain... (Randomized Controlled Trial)
Randomized Controlled Trial
Level of pain catastrophising determines if patients with long-standing subacromial impingement benefit from more resistance exercise: predefined secondary analyses from a pragmatic randomised controlled trial (the SExSI Trial).
OBJECTIVE
The primary aim was to investigate the effectiveness of adding more resistance exercise to usual care on pain mechanisms (including temporal summation, conditioned pain modulation (CPM) and local pain sensitivity) and pain catastrophising in people with subacromial impingement at 16 weeks follow-up. Second, to investigate the modifying effect of pain mechanisms and pain catastrophising on the interventions' effectiveness in improving shoulder strength and disability METHODS: 200 consecutive patients were randomly allocated to usual exercise-based care or the same plus additional elastic band exercise to increase total exercise dose. Completed add-on exercise dose was captured using an elastic band sensor. Outcome measures recorded at baseline, 5 weeks, 10 weeks and 16 (primary end point) weeks included temporal summation of pain (TSP) and CPM assessed at the lower leg, pressure pain threshold at the deltoid muscle (PPT-deltoid), pain catastrophising and the Shoulder Pain and Disability Index.
RESULTS
Additional elastic band exercise was not superior to usual exercise-based care in improving pain mechanisms (TSP, CPM and PPT-deltoid) or pain catastrophising after 16 weeks. Interaction analyses showed that pain catastrophising (median split) modified the effectiveness of additional exercises (effect size 14 points, 95% CI 2 to 25), with superior results in the additional exercise group compared with the usual care group in patients with less pain catastrophising.
CONCLUSION
Additional resistance exercise added to usual care was not superior to usual care alone in improving pain mechanisms or pain catastrophising. Additional exercise was, however, superior in improving self-reported disability in patients with lower levels of pain catastrophising at baseline.
TRIAL REGISTRATION NUMBER
NCT02747251.
Topics: Humans; Resistance Training; Shoulder Impingement Syndrome; Exercise Therapy; Physical Therapy Modalities; Shoulder Pain
PubMed: 36898767
DOI: 10.1136/bjsports-2022-106383 -
Musculoskeletal Science & Practice Aug 2023Office workers are specifically vulnerable to headache conditions. Neck pain is reported by almost 80% of patients with headaches. Associations between currently... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Office workers are specifically vulnerable to headache conditions. Neck pain is reported by almost 80% of patients with headaches. Associations between currently recommended tests to examine cervical musculoskeletal impairments, pressure pain sensitivity and self-reported variables in headache, are unknown. The aim of this study is to evaluate whether cervical musculoskeletal impairments and pressure pain sensitivity are associated with self-reported headache variables in office workers.
METHODS
This study reports a cross-sectional analysis using baseline data of a randomized controlled trial. Office workers with headache were included in this analysis. Multivariate associations, controlled for age, sex and neck pain, between cervical musculoskeletal variables (strength, endurance, range of motion, movement control) and pressure pain threshold (PPT) over the neck and self-reported headache variables, such as frequency, intensity, and the Headache-Impact-Test-6, were examined.
RESULTS
Eighty-eight office workers with a 4-week headache frequency of 4.8 (±5.1) days, a moderate average headache intensity (4.5 ± 2.1 on the NRS), and "some impact" (mean score: 53.7 ± 7.9) on the headache-impact-test-6, were included. Range of motion and PPT tested over the upper cervical spine were found to be most consistently associated with any headache variable. An adjusted R of 0.26 was found to explain headache intensity and the score on the Headache-Impact-Test-6 by several cervical musculoskeletal and PPT variables.
DISCUSSION
Cervical musculoskeletal impairments can explain, irrespective of coexisting neck pain, only little variability of the presence of headache in office workers. Neck pain is likely a symptom of the headache condition, and not a separate entity.
Topics: Humans; Pain Threshold; Neck Pain; Cross-Sectional Studies; Headache; Cervical Vertebrae
PubMed: 37394322
DOI: 10.1016/j.msksp.2023.102816 -
Pain Reports Jan 2024Fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) are distinct pain conditions that share commonalities and may be challenging as for differential diagnosis.
INTRODUCTION
Fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) are distinct pain conditions that share commonalities and may be challenging as for differential diagnosis.
OBJECTIVE
To comprehensively investigate clinical characteristics of women with FMS and SFN to determine clinically applicable parameters for differentiation.
METHODS
We retrospectively analyzed medical records of 158 women with FMS and 53 with SFN focusing on pain-specific medical and family history, accompanying symptoms, additional diseases, and treatment. We investigated data obtained using standardized pain, depression, and anxiety questionnaires. We further analyzed test results and findings obtained in standardized small fiber tests.
RESULTS
FMS patients were on average ten years younger at symptom onset, described higher pain intensities requiring frequent change of pharmaceutics, and reported generalized pain compared to SFN. Pain in FMS was accompanied by irritable bowel or sleep disturbances, and in SFN by paresthesias, numbness, and impaired glucose metabolism ( < 0.01 each). Family history was informative for chronic pain and affective disorders in FMS ( < 0.001) and for neurological disorders in SFN patients ( < 0.001). Small fiber pathology in terms of skin denervation and/or thermal sensory threshold elevation was present in 110/158 (69.7 %) FMS patients and 39/53 (73.6 %) SFN patients. FMS patients mainly showed proximally reduced skin innervation and higher corneal nerve branch densities (p<0.001) whereas SFN patients were characterized by reduced cold detection and prolonged electrical A-delta conduction latencies ( < 0.05).
CONCLUSIONS
Our data show that FMS and SFN differ substantially. Detailed pain, drug and family history, investigating blood glucose metabolism, and applying differential small fiber tests may help to improve diagnostic differentiation and targeted therapy.
PubMed: 38283649
DOI: 10.1097/PR9.0000000000001136 -
Gerontology & Geriatric Medicine 2023The prevalence of chronic pain increases with age. It has been reported that chronic pain is associated with sarcopenia and obesity. Age-related skeletal muscle loss...
The prevalence of chronic pain increases with age. It has been reported that chronic pain is associated with sarcopenia and obesity. Age-related skeletal muscle loss and fat gain are known to occur due to chronic inflammation. The aim of this study was to analyze how skeletal muscle and fat, caused by chronic inflammation due to aging, regulate the development of geriatric chronic pain. The results of skeletal muscle and fat mass, 412 participants aged ≥65 years with non-specific chronic pain lasting ≥6 months, including low back, neck, and knee pain, was compared with the control without chronic pain. Body composition threshold regulating chronic pain was calculated. A significantly lower skeletal muscle mass index and higher body fat percentage were observed in patients with chronic pain than that in the control. The muscle fat ratio (MFR) was significantly lower in the chronic pain group than in the control group. When the MFR threshold related to chronic pain was calculated by sex, it was 2.984 for men and 1.867 for women. Evaluation of the body composition of elderly patients with non-specific chronic pain revealed that the MFR was useful as an index related to chronic pain.
PubMed: 37533769
DOI: 10.1177/23337214231190146 -
BMC Women's Health Nov 2023The purpose was to compare the effects of manual lymphatic drainage and soft tissue mobilization on pain threshold, shoulder mobility and quality of life in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparative effects of lymphatic drainage and soft tissue mobilization on pain threshold, shoulder mobility and quality of life in patients with axillary web syndrome after mastectomy.
PURPOSE
The purpose was to compare the effects of manual lymphatic drainage and soft tissue mobilization on pain threshold, shoulder mobility and quality of life in patients with axillary web syndrome.
METHODS
This randomized clinical trial was conducted on 36 breast cancer patients with developed axillary web; participants were randomly divided into two groups. One group was treated with manual lymphatic drainage; the other group was treated with soft tissue mobilizations in addition to therapeutic exercises, i.e., stretching, strengthening and range of motion (ROM) exercises. The duration of treatment was four weeks (5 sessions/week), with therapeutic exercises as a common treatment protocol. Outcome measures were Breast-Cancer specific quality of life questionnaires, Disabilities of the Arm, Shoulder and Hand (DASH), Numeric Pain Rating Scale (NPRS), Patient Specific Functional Scale (PSFS), Dynamometer and Goniometer. All outcome measure readings were recorded at baseline and the end (4th week) of the treatment.
RESULTS
The compliance of the variable distribution with normal distribution was verified using the Shaphiro-Wilk test. Parametric tests were applied, and both groups showed significant effects (p < 0.05) in pairwise comparison (paired t-test). The comparison group analysis (independent t-test) showed that there was no significant difference in pain, upper limb strength, range of motions and fatigue component of quality of life questionnaire parameters (p > 0.05). Two parameters (DASH, PSFS) and one component of the quality of life questionnaire (global health) showed a significant difference (p < 0.05).
CONCLUSION
Manual lymphatic drainage showed more improvement in functional movements. It was concluded that both groups, manual lymphatic drainage and soft tissue mobilization groups were clinically equally effective.
TRIAL REGISTRATION NUMBER
This trial is registered at ClinicalTrial.gov PRS under trial number NCT05463185 on date 18/07/2022.
Topics: Humans; Female; Shoulder; Mastectomy; Breast Neoplasms; Pain Threshold; Quality of Life; Upper Extremity; Pain; Range of Motion, Articular; Treatment Outcome
PubMed: 37950230
DOI: 10.1186/s12905-023-02762-w -
Journal of Pain Research 2023To assess the inhibitory effect of acupuncture on pain symptoms in migraine models, and to further summarize the potential mechanisms of acupuncture in regulating... (Review)
Review
PURPOSE
To assess the inhibitory effect of acupuncture on pain symptoms in migraine models, and to further summarize the potential mechanisms of acupuncture in regulating hyperalgesia in the treatment of migraine.
MATERIALS AND METHODS
Literature search in databases such as China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science (WOS) etc. The quality was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) bias risk assessment tool and Collaborative Approach to Meta-analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Meta-analyses were performed using Stata 17.0 software.
RESULTS
Twenty-one studies involving 489 animals were identified. The qualitative score ranged from 3 to 9 points. Facial mechanical withdrawal threshold (FMWT) and paw mechanical withdrawal threshold (PMWT) measured by Von Frey filaments were selected as major outcomes, and serum calcitonin gene-related peptide (CGRP) levels measured by ELISA were selected as secondary outcome. Meta-analysis results revealed that true acupuncture (TA) group significantly increased FMWT, PMWT and CGRP compared to model group. TA group showed superior effect in FMWT, PMWT relative to sham acupuncture (SA) group. Subgroup analysis results showed that high risk of bias scores may be responsible for the high heterogeneity of FMWT; additionally, CGRP analysis suggests that acupoint selection and blood collection sites may be sources of heterogeneity. In the treatment of migraine pain symptoms, the underlying mechanism of acupuncture treatment is either the regulation of hyperalgesia and neurotransmitters, or the reduction of inflammatory factors.
CONCLUSION
The results indicate that TA treatment effectively increased the pain threshold and reduced hyperalgesia in migraine rats. In summary, our study highlights the potential of TA as an effective treatment for migraine, but further investigation is required to fully comprehend its mechanism of action and optimize its clinical application.
PubMed: 37521010
DOI: 10.2147/JPR.S422050 -
Complementary Therapies in Medicine Oct 2023Clarifying the effect of music on pain endurance in an experimental design could aid in how music should be applied during both surgical and non-surgical interventions.... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Clarifying the effect of music on pain endurance in an experimental design could aid in how music should be applied during both surgical and non-surgical interventions. This study aims to investigate the effect of music on pain endurance and the involvement of the sympathetic adrenomedullary axis (SAM) and the hypothalamic-pituitary-adrenocortical axis (HPA).
MATERIALS AND METHODS
In this randomized controlled trial all participants received increasing electric stimuli through their non-dominant index finger. Participants were randomly assigned to the music group (M) receiving a 20-minute music intervention or control group (C) receiving a 20-minute resting period. The primary outcome was pain endurance, defined as amount milliampere tolerated. Secondary outcomes included anxiety level, SAM-axis based on heart rate variability (HRV) and salivary alpha-amylase, and HPA-axis activity based on salivary cortisol.
RESULTS
In the intention-to-treat analysis, the effect of music on pain tolerance did not statistically differ between the M and C group. A significant positive effect of music on pain endurance was noted after excluding participants with a high skin impedance (p = 0.013, CI 0.35; 2.85). Increased HRV was observed in the M-group compared to the C-group for SDNN (B/95%CI:13.80/2.22;25.39, p = 0.022), RMSSD (B/95%CI:15.97/1.64;30.31, p = 0.032), VLF (B/95%CI:212.08/60.49;363.67, p = 0.008) and HF (B/95%CI:821.15/150.78;1491.52, p = 0.0190). No statistical significance was observed in other secondary outcomes.
CONCLUSIONS
The effect of the music intervention on pain endurance was not statistically significant in the intention-to-treat analysis. The subgroup analyses revealed an increase in pain endurance in the music group after correcting for skin impedance, which could be attributed to increased parasympathetic activation.
Topics: Humans; Music; Pain; Music Therapy; Heart Rate; Pain Threshold; Anxiety
PubMed: 37579996
DOI: 10.1016/j.ctim.2023.102969 -
Physiotherapy Jun 2024Every second human will experience a phase of neck pain in their lifetime and a high rate of chronicity exists. Because of the complexity and multiple influencing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Every second human will experience a phase of neck pain in their lifetime and a high rate of chronicity exists. Because of the complexity and multiple influencing factors, chronic pain conditions are associated with a long treatment and diagnostic process. This leads to a prolonged healing process and high costs.
OBJECTIVE
To evaluate the effect of myofascial release on the variables of pain and range of motion in patients with chronic neck pain.
METHOD
Selection criteria were set to create a search algorithm for a systematic search in the databases: PubMed, Google Scholar, EBM Reviews, Medline, CINAHL, PEDro, and Science Direct. The risk of bias and the methodological quality was analyzed with the PEDro scale.
RESULT
Ten randomized controlled trials, with 549 participants met the eligibility criteria. The methodological quality was ranked from good to excellent. The myofascial release showed a significant difference in pain (p = 0.03), rotation to the right (p = 0.05), and lateral flexion to the right (p = 0.04), compared to other treatment methods. No significant effect was found for improvements in pressure pain threshold.
CONCLUSION
Modest effects are observed in pain reduction, suggesting potential benefits of myofascial release in managing chronic neck pain. Further research with standardized protocols and direct comparisons to established therapies is crucial for a comprehensive understanding of myofascial release efficacy.
CONTRIBUTION OF THE PAPER
What does the meta-analysis add to the current literature.
Topics: Humans; Neck Pain; Chronic Pain; Range of Motion, Articular; Randomized Controlled Trials as Topic; Adult; Pain Measurement
PubMed: 38290198
DOI: 10.1016/j.physio.2023.12.002 -
Brazilian Oral Research 2023This study aimed to evaluate the association of pain-related disability with biopsychosocial factors in temporomandibular disorders (TMD) patients. The study was carried...
This study aimed to evaluate the association of pain-related disability with biopsychosocial factors in temporomandibular disorders (TMD) patients. The study was carried out at the Orofacial Pain Outpatient Clinic of the State University of Feira de Santana, Bahia, from September 2018 to March 2020. The sociodemographic aspects, TMD subtypes, presence of pain-induced disability, pressure pain threshold, perceived stress, anxiety, depression, and catastrophizing were evaluated in 61 patients. The studied variables were compared between patients with and without pain-induced disability. Crude and adjusted logistic regression were performed to obtain estimates of odds ratios (OR) and 95% confidence intervals. With the exception of catastrophizing, there was no association between the biopsychosocial factors and pain-induced disability. The presence of catastrophizing increased the chance of having chronic pain-induced disability by 4.02 times. The results of this study indicate a strong association between pain catastrophizing and disability in individuals with chronic painful TMD.
Topics: Humans; Catastrophization; Chronic Pain; Anxiety; Pain Measurement; Temporomandibular Joint Disorders
PubMed: 37436293
DOI: 10.1590/1807-3107bor-2023.vol37.0070