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Environmental Health and Preventive... 2024Methylmercury (MeHg), the causative agent of Minamata disease, damages the cranial nervous system and causes specific sensory disturbances, especially hypoesthesia, in...
BACKGROUND
Methylmercury (MeHg), the causative agent of Minamata disease, damages the cranial nervous system and causes specific sensory disturbances, especially hypoesthesia, in the extremities. However, recent reports demonstrate that patients with chronic Minamata disease conversely develop neuropathic pain in the lower extremities. Studies on our established Minamata disease model rats showed that MeHg-mediated neurodegeneration might induce neuropathic pain by over time through inducing rewiring with neuronal activation in the somatosensory cortex via microglial activation in the spinal dorsal horn.
METHODS
In this study, the effects of gabapentin, a potentially effective treatment for neuropathic pain, was evaluated using this Minamata disease model rats. To further elucidate the mechanism of its medicinal effects, histochemical and biochemical analyses of the nervous system of Minamata disease model rats were conducted.
RESULTS
Gabapentin treatment restored the reduction in the pain threshold caused by MeHg exposure in rats. Histochemical and biochemical analyses revealed that gabapentin showed no effect on MeHg-induced neurodegeneration in entire nervous system and microglial activation in the spinal dorsal horn. However, it was shown that gabapentin may reduce excessive synaptogenesis through its antagonist action on the alpha2-delta-1 subunit of calcium channels in the somatosensory cortex.
CONCLUSIONS
These results indicate that gabapentin may alleviated neuropathic pain in MeHg poisoning, as typified by Minamata disease, by reversibly modulation synaptic rewiring in the somatosensory cortex.
Topics: Animals; Gabapentin; Neuralgia; Rats; Male; Disease Models, Animal; Methylmercury Compounds; Analgesics; Amines; Cyclohexanecarboxylic Acids; gamma-Aminobutyric Acid; Rats, Wistar
PubMed: 38825526
DOI: 10.1265/ehpm.24-00035 -
The Lancet. Rheumatology Jul 2024Low back pain is prevalent and a leading cause of disability. We aimed to determine the clinical and cost-effectiveness of an accessible, scalable internet intervention... (Randomized Controlled Trial)
Randomized Controlled Trial
Supporting self-management of low back pain with an internet intervention with and without telephone support in primary care (SupportBack 2): a randomised controlled trial of clinical and cost-effectiveness.
BACKGROUND
Low back pain is prevalent and a leading cause of disability. We aimed to determine the clinical and cost-effectiveness of an accessible, scalable internet intervention for supporting behavioural self-management (SupportBack).
METHODS
Participants in UK primary care with low back pain without serious spinal pathology were randomly assigned 1:1:1 using computer algorithms stratified by disability level and telephone-support centre to usual care, usual care and SupportBack, or usual care and SupportBack with physiotherapist telephone-support (three brief calls). The primary outcome was low back pain-related disability (Roland Morris Disability Questionnaire [RMDQ] score) at 6 weeks, 3 months, 6 months, and 12 months using a repeated measures model, analysed by intention to treat using 97·5% CIs. A parallel economic evaluation from a health services perspective was used to estimate cost-effectiveness. People with lived experience of low back pain were involved in this trial from the outset. This completed trial was registered with ISRCTN, ISRCTN14736486.
FINDINGS
Between Nov 29, 2018, and Jan 12, 2021, 825 participants were randomly assigned (274 to usual care, 275 to SupportBack only, 276 to SupportBack with telephone-support). Participants had a mean age of 54 (SD 15), 479 (58%) of 821 were women and 342 (42%) were men, and 591 (92%) of 641 were White. Follow-up rates were 687 (83%) at 6 weeks, 598 (73%) at 3 months, 589 (72%) at 6 months, and 652 (79%) at 12 months. For the primary analysis, 736 participants were analysed (249 usual care, 245 SupportBack, and 242 SupportBack with telephone support). At a significance level of 0·025, there was no difference in RMDQ over 12 months with SupportBack versus usual care (adjusted mean difference -0·5 [97·5% CI -1·2 to 0·2]; p=0·085) or SupportBack with telephone-support versus usual care (-0·6 [-1·2 to 0·1]; p=0·048). There were no treatment-related serious adverse events. The economic evaluation showed that the SupportBack group dominated usual care, being both more effective and less costly. Both interventions were likely to be cost-effective at a threshold of £20 000 per quality adjusted life year compared with usual care.
INTERPRETATION
The SupportBack internet interventions did not significantly reduce low back pain-related disability over 12 months compared with usual care. They were likely to be cost-effective and safe. Clinical effectiveness, cost-effectiveness, and safety should be considered together when determining whether to apply these interventions in clinical practice.
FUNDING
National Institute for Health and Care Research Health Technology Assessment (16/111/78).
Topics: Humans; Low Back Pain; Cost-Benefit Analysis; Female; Male; Middle Aged; Primary Health Care; Self-Management; Telephone; Adult; Internet-Based Intervention; Treatment Outcome; United Kingdom; Disability Evaluation; Internet
PubMed: 38824934
DOI: 10.1016/S2665-9913(24)00086-9 -
Chiropractic & Manual Therapies May 2024Clinical practice guidelines recommend spinal manipulation for patients with low back pain. However, the effects of spinal manipulation have contradictory findings... (Randomized Controlled Trial)
Randomized Controlled Trial
One spinal manipulation session reduces local pain sensitivity but does not affect postural stability in individuals with chronic low back pain: a randomised, placebo-controlled trial.
BACKGROUND
Clinical practice guidelines recommend spinal manipulation for patients with low back pain. However, the effects of spinal manipulation have contradictory findings compared to placebo intervention. Therefore, this study investigated the immediate effects of lumbar spinal manipulation on pressure pain threshold (PPT) and postural stability in people with chronic low back pain (cLBP). Second, we investigated the immediate effect of lumbar spinal manipulation on pain intensity and the interference of the participant beliefs about which treatment was received in the PPT, postural stability, and pain intensity.
METHODS
A two-arm, randomised, placebo-controlled, double-blind trial was performed. Eighty participants with nonspecific cLPB and a minimum score of 3 on the Numeric Pain Rating Scale received one session of lumbar spinal manipulation (n = 40) or simulated lumbar spinal manipulation (n = 40). Primary outcomes were local and remote PPTs and postural stability. Secondary outcomes were pain intensity and participant's perceived treatment allocation. Between-group mean differences and their 95% confidence intervals (CIs) estimated the treatment effect. One-way analysis of covariance (ANCOVA) was performed to assess whether beliefs about which treatment was received influenced the outcomes.
RESULTS
Participants had a mean (SD) age of 34.9 (10.5) years, and 50 (62.5%) were women. Right L5 [between-group mean difference = 0.55 (95%CI 0.19 to 0.90)], left L5 [between-group mean difference = 0.45 (95%CI 0.13 to 0.76)], right L1 [between-group mean difference = 0.41 (95%CI 0.05 to 0.78)], left L1 [between-group mean difference = 0.57 (95%CI 0.15 to 0.99)], left DT [between-group mean difference = 0.35 (95%CI 0.04 to 0.65)], and right LE [between-group mean difference = 0.34 (95%CI 0.08 to 0.60)] showed superior treatment effect in the spinal manipulation group than sham. Neither intervention altered postural stability. Self-reported pain intensity showed clinically significant decreases in both groups after the intervention. A higher proportion of participants in the spinal manipulation group achieved more than two points of pain relief (spinal manipulation = 90%; sham = 60%). The participants' perceived treatment allocation did not affect the outcomes.
CONCLUSION
One spinal manipulation session reduces lumbar pain sensitivity but does not affect postural stability compared to a sham session in individuals with cLPB. Self-reported pain intensity lowered in both groups and a higher proportion of participants in the spinal manipulation group reached clinically significant pain relief. The participant's belief in receiving the manipulation did not appear to have influenced the outcomes since the adjusted model revealed similar findings.
Topics: Humans; Low Back Pain; Female; Manipulation, Spinal; Male; Adult; Double-Blind Method; Postural Balance; Pain Threshold; Middle Aged; Pain Measurement; Chronic Pain; Treatment Outcome
PubMed: 38822395
DOI: 10.1186/s12998-024-00541-4 -
International Journal of Pharmaceutics Jun 2024Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is...
Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is one of the most significant areas of clinical medicine and basic research. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. A medicinal preparation is required that relieves the neuropathic pain and prolongs action time, which has not yet been discovered. In this study, MIL-101 (Fe) was employed as a drug carrier to regulate the release of diclofenac sodium, thereby achieving the effect of analgesia and sustained release. The release curves demonstrated that diclofenac sodium could be continuously released from MIL-101 (Fe) for more than 48 h. There was no toxicity in vitro and in vivo, and the safety of MIL-101 (Fe) was confirmed by hematoxylin and eosin as well as ELISA tests in vivo. The results of behavioral testing, pharmacokinetics, and RNA sequencing analysis showed that MIL-101 (Fe) loaded with diclofenac sodium could enhance the mechanical withdrawal threshold and alleviate cold allodynia induced by Spared Nerve Injury, prolonging the work time by three days. The results indicated that MIL-101 (Fe) exhibited excellent biocompatibility, while the MIL-101 (Fe)-DS demonstrated analgesic and controlled-release properties. These findings provide a scientific foundation for the clinical management of neuropathic pain and the development of a novel formulation.
Topics: Animals; Diclofenac; Neuralgia; Male; Rats, Sprague-Dawley; Spinal Cord; Transcriptome; Nanomedicine; Rats; Drug Carriers; Anti-Inflammatory Agents, Non-Steroidal; Drug Liberation; Delayed-Action Preparations; Disease Models, Animal; Hyperalgesia
PubMed: 38821436
DOI: 10.1016/j.ijpharm.2024.124276 -
PloS One 2024People experiencing homelessness are more likely to experience poor health with physical functioning deficits and frailty commonly reported. It is not well known how... (Clinical Trial)
Clinical Trial
Outcomes of the LEAP feasibility trial-A low-threshold, exercise programme with protein supplementation to target frailty and poor physical functioning in people experiencing homelessness and addiction issues.
BACKGROUND
People experiencing homelessness are more likely to experience poor health with physical functioning deficits and frailty commonly reported. It is not well known how strategies to target physical functioning deficits and frailty work in practice in this group. The primary aim of this study was to explore the feasibility of an exercise intervention with protein supplementation to target physical functioning and frailty in people experiencing homelessness evaluated by recruitment and retention rates, adherence to the exercise sessions and protein supplement, adverse effects, programme feedback and characteristics of non-returners, sporadic and frequent attenders. The secondary aim was to evaluate changes in effectiveness outcomes of grip strength, muscle mass, lower extremity physical function, pain, frailty, and risk of malnutrition.
METHOD
This prospective single-arm study evaluated the feasibility of a 16-week rolling, low-threshold, 'drop-in' once weekly exercise programme with protein supplementation. The main recruitment site was a day-service centre for people who are homeless. Feasibility was assessed by the recruitment and retention rates, adherence to the exercise sessions and protein supplement as well as adverse effects, programme feedback and evaluation of characteristics of non-returners, sporadic (≤50% of available sessions) and frequent attenders (≥50% of available sessions). Effectiveness outcomes included pain (Visual Analogue Scale), physical functioning and performance (hand-grip dynamometry, limb circumference, the Short Physical Performance Battery), frailty (SHARE-FI and Clinical Frailty Scale) and nutritional status (Mini Nutritional Assessment).
RESULTS
Thirty-one participants were recruited mean (SD) age 45(16) years. There was a recruitment rate of a median (IQR) of 2(1-3) new participants per week. The retention rate was 45% (n = 14) to the main recruitment site. Adherence to the exercise sessions and nutritional intervention was 90% and 100% respectively. Three adverse events were recorded during 74 interventions over the 16-week programme. The acceptability of the programme was highlighted in participant feedback. Characteristics of frequent returners (≥50%) were older age, female, more stably housed and more stable in addiction. The programme did not induce any changes in effectiveness outcomes.
CONCLUSION
The feasibility of this programme was demonstrated. Overall, the programme was well received with higher retention rates in older participants, females, those more stably housed and those stable in addiction. A higher powered, more intense programme is needed to demonstrate programme effectiveness.
Topics: Humans; Male; Female; Middle Aged; Feasibility Studies; Exercise Therapy; Dietary Supplements; Frailty; Ill-Housed Persons; Adult; Prospective Studies; Dietary Proteins; Hand Strength; Aged; Exercise
PubMed: 38820432
DOI: 10.1371/journal.pone.0301926 -
Molecular Pain 2024This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an...
This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.
Topics: Animals; Male; Female; Fibromyalgia; Ganglia, Spinal; Rats, Sprague-Dawley; Extracellular Signal-Regulated MAP Kinases; Sex Characteristics; Phosphorylation; Rats; Pain Threshold; Disease Models, Animal; Pain
PubMed: 38818809
DOI: 10.1177/17448069241261940 -
BMC Emergency Medicine May 2024External bleeding is the leading cause of preventable trauma-related death. In certain circumstances, tourniquet application over clothing may be necessary. Therefore,...
INTRODUCTION
External bleeding is the leading cause of preventable trauma-related death. In certain circumstances, tourniquet application over clothing may be necessary. Therefore, the aim of this study was to assess the effectiveness of tourniquets over different clothing setups.
METHODS
Three windlass tourniquets (CAT, SAMXT, SOFTT-W) were applied over nine different clothing setups and without clothing on the Hapmed™ Tourniquet Trainer. We compared each tourniquet in each clothing setup to the tourniquet trainer that was not dressed, and we compared the three tourniquets within each clothing setup concerning blood loss, applied pressure and application time. Regression analysis of the effect of thickness, mean weight, mean deformation, application time, and applied pressure on blood loss was performed.
RESULTS
Although blood loss was significantly greater in the CAT and SAMXT tourniquets when they were applied over leather motorcycle trousers, the overall findings showed that the clothing setups significantly reduced or did not affect blood loss. The mean blood loss was the lowest with CAT and the highest with SOFTT-W. The measured mean pressures were lower than 180 mmHg in four out of nine clothing setups with SOFTT-W, but CAT and SAMXT always exceeded this threshold. CAT had the fastest application time. Blood loss was significantly influenced by applied pressure and application time but was influenced to a far lesser degree by clothing parameters.
CONCLUSION
The effects of the clothing setups were of little clinical relevance, except for leather motorcycle trousers. The effects of rugged protective equipment, e.g., hazard suits, are conceivable and need to be tested for specific garments with the tourniquet intended for use. No clothing parameter for predicting tourniquet effectiveness could be identified.
Topics: Tourniquets; Humans; Clothing; Hemorrhage; Equipment Design
PubMed: 38816683
DOI: 10.1186/s12873-024-01005-x -
Journal of Applied Physiology... May 2024Pain is a naturally occurring phenomenon that consistently inhibits exercise performance by imposing unconscious, neurophysiological alterations (e.g., corticospinal...
Pain is a naturally occurring phenomenon that consistently inhibits exercise performance by imposing unconscious, neurophysiological alterations (e.g., corticospinal changes) as well as conscious, psychophysiological pressures (e.g., shared effort demands). Although, several studies indicate that pain would elicit lower task outputs for a set intensity of perceived effort, no study has tested this. Therefore, this study investigated the impact of elevated muscle pain through a hypertonic saline injection on the power output, psychophysiological, cerebral oxygenation, and perceptual changes during fixed perceived effort exercise. Ten participants completed three visits (one familiarisation + two fixed perceived effort trials). Fixed perceived effort cycling corresponded to 15% above gas exchange threshold (mean RPE = 15; hard). Before the 30-minute fixed perceived effort exercise, participants received a randomised, bilateral hypertonic or isotonic saline injection in the vastus lateralis. Power output, cardiorespiratory, cerebral oxygenation, and perceptual markers (e.g., affective valence) were recorded during exercise. Linear mixed model regression assessed the condition and time effects and condition × time interactions. Significant condition effects showed that power output was significantly lower during hypertonic conditions (t_107= 2.08,p=.040,β=4.77 Watts,95%CI [0.27 to 9.26 Watts]). Meanwhile all physiological variables (e.g., heart rate, oxygen uptake, minute ventilation) demonstrated no significant condition effects. Condition effects were observed for deoxyhaemoglobin changes from baseline (t_107= -3.29,p=.001,β=-1.50 ΔµM,95%CI [-2.40 to-0.61 ΔµM]) and affective valence (t_127= 6.12,p=.001,β=0.93,95%CI [0.63,1.23]). Results infer that pain impacts the self-regulation of fixed perceived effort exercise, as differences in power output mainly occurred when pain ratings were higher after hypertonic versus isotonic saline administration.
PubMed: 38813614
DOI: 10.1152/japplphysiol.00325.2023 -
Turkish Journal of Medical Sciences 2023To compare the effectiveness of instrument-assisted soft tissue mobilization (IASTM) and extracorporeal shock wave therapy (ESWT) used in myofascial pain syndrome (MPS)... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND/AIM
To compare the effectiveness of instrument-assisted soft tissue mobilization (IASTM) and extracorporeal shock wave therapy (ESWT) used in myofascial pain syndrome (MPS) and to determine whether they are superior to conservative treatment (CT).
MATERIALS AND METHODS
A total of 42 female patients (aged 18-60 years) diagnosed with MPS were enrolled and randomly assigned to either the CT (n = 14), CT+IASTM (n = 14), or CT+ESWT group (n = 14). All of the groups received treatment for 3 weeks (CT: 5 sessions per week, 15 sessions in total, ESWT and IASTM: 2 sessions per week, 6 sessions in total). Neck stretching exercises were given to all of the patients as a home program. The pain intensity of the patients was determined using the visual analog scale (VAS). The pressure pain threshold (PPT) was measured with an algometer. Cervical joint range of motion (ROM) was measured with a cervical ROM (CROM) device. Pain, cervical disability, quality of life, and sleep disturbances were evaluated with the Neck Outcome Score (NOOS). Depression and anxiety parameters were evaluated with the Hospital Anxiety and Depression Scale (HADS). Evaluations were made before treatment and 3 days after the last treatment session.
RESULTS
The CT+IASTM group was more successful than the other groups in terms of pain intensity, PPT, and improvements in the ROM parameters (p < 0.05). No significant difference was found between the NOOS and HADS scores of the groups when the posttreatment changes were compared to pretreatment (p > 0.05).
CONCLUSIONS
All 3 of these treatments can be used to alleviate the negative effects of MPS. IASTM treatment can be preferred primarily in the creation of combined treatment programs for patients with ROM limitations and low PPTs.
Topics: Humans; Female; Adult; Extracorporeal Shockwave Therapy; Myofascial Pain Syndromes; Middle Aged; Young Adult; Treatment Outcome; Range of Motion, Articular; Adolescent; Pain Measurement; Quality of Life; Therapy, Soft Tissue
PubMed: 38813497
DOI: 10.55730/1300-0144.5753 -
Journal of Pain Research 2024Central sensitization (CS) has been proposed as a possible contributor to persistent shoulder pain. Measures of sensitivity, such as quantitative sensory tests (QSTs)...
BACKGROUND
Central sensitization (CS) has been proposed as a possible contributor to persistent shoulder pain. Measures of sensitivity, such as quantitative sensory tests (QSTs) and sensitivity to movements evoked pain (SMEP), have been increasingly used to investigate CS in a wide range of painful conditions. However, there is a lack of data on whether QST and SMEP are reliable among individuals with shoulder pain. Therefore, the present study aimed to investigate the intra-rater test-retest reliability of QST and SMEP in individuals with chronic shoulder pain.
MATERIALS AND METHODS
Forty-seven individuals with chronic shoulder pain were enrolled in the study. The QST measures, including pressure pain threshold (PPT) and mechanical temporal summation (MTS), were tested, and SMEP was measured with a lifting task. Relative and absolute reliability were analyzed using intraclass correlation coefficients (ICC 3,1) and standard error of the measurement (SEM), respectively.
RESULTS
The results showed that the ICC coefficients for all sensitivity measures were moderate to good, ranging from 0.63 to 0.86. The SEM% for the QST measures at all sites ranged from 21.4% to 36%, with TS at the forearm demonstrating a high SEM% (greater than 30%). The SMEP measure also showed a high SEM% (46%).
CONCLUSION
The results showed that the sensitivity measures had moderate to good reliability among individuals with shoulder pain. Acceptable limits of accuracy of measurements were demonstrated for TS and PPT measures, while SMEP demonstrated high error, highlighting the need for further refinement of this measure among these populations.
PubMed: 38812821
DOI: 10.2147/JPR.S456551