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Molecules (Basel, Switzerland) Apr 2024Various plant species from the genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic... (Review)
Review
Various plant species from the genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine species including (1) , (2) , (3) , (4) , (5) , (6) , (7) , (8) and (9) . Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HTR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the plants. Overall, the findings suggested species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.
Topics: Litsea; Analgesics; Animals; Plant Extracts; Pain; Humans
PubMed: 38731572
DOI: 10.3390/molecules29092079 -
Pharmaceuticals (Basel, Switzerland) Nov 2023Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as... (Review)
Review
BACKGROUND
Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans.
METHODS
Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots.
RESULTS
Sixteen eligible articles, including k = 5 studies of pain tolerance ( = 210), k = 5 studies of pain threshold ( = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges' g = 0.28, 95% CI = 0-0.55, Z = 1.99, = 0.05) and pain tolerance (Hedges' g = 0.32, 95% CI = 0.05-0.59, Z = 2.30, = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of -0.37 (95% CI = -0.77 to 0.03, Z = -1.80) but with no statistical significance ( = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges' g = 0.37, 95% CI = 0.29-0.64, Z = 5.33, < 0.01).
CONCLUSION
These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
PubMed: 38139792
DOI: 10.3390/ph16121665 -
Pain May 2024Recent literature suggests that the withdrawal of remifentanil (RF) infusion can be associated with hyperalgesia in clinical and nonclinical settings. We performed a... (Meta-Analysis)
Meta-Analysis
Recent literature suggests that the withdrawal of remifentanil (RF) infusion can be associated with hyperalgesia in clinical and nonclinical settings. We performed a systematic review and a meta-analysis of randomized controlled trials with cross-over design, to assess the effect of discontinuing RF infusion on pain intensity and areas of hyperalgesia and allodynia in healthy volunteers. Nine studies were included. The intervention treatment consisted in RF infusion that was compared with placebo (saline solution). The primary outcome was pain intensity assessment at 30 ± 15 minutes after RF or placebo discontinuation, assessed by any pain scale and using any quantitative sensory testing. Moreover, postwithdrawal pain scores were compared with baseline scores in each treatment. Secondary outcomes included the areas (% of basal values) of hyperalgesia and allodynia. Subjects during RF treatment reported higher pain scores after discontinuation than during treatment with placebo [standardized mean difference (SMD): 0.50, 95% confidence interval (CI): 0.03-0.97; P = 0.04, I 2 = 71%]. A significant decrease in pain scores, compared with baseline values, was found in the placebo treatment (SMD: -0.87, 95% CI: -1.61 to -0.13; P = 0.02, I 2 = 87%), but not in the RF treatment (SMD: -0.28, 95% CI: -1.18 to 0.62; P = 0.54, I 2 = 91%). The area of hyperalgesia was larger after RF withdrawal (SMD: 0.55; 95% CI: 0.27-0.84; P = 0.001; I 2 = 0%). The area of allodynia did not vary between treatments. These findings suggest that the withdrawal of RF induces a mild but nonclinically relevant degree of hyperalgesia in HVs, likely linked to a reduced pain threshold.
Topics: Humans; Remifentanil; Hyperalgesia; Analgesics, Opioid; Piperidines; Randomized Controlled Trials as Topic; Pain
PubMed: 38047761
DOI: 10.1097/j.pain.0000000000003119 -
Neurospine Sep 2023The objective of this systematic review and meta-analysis was to assess the efficacy of exercise in neuropathic pain following traumatic spinal cord injuries.
OBJECTIVE
The objective of this systematic review and meta-analysis was to assess the efficacy of exercise in neuropathic pain following traumatic spinal cord injuries.
METHODS
The search was conducted in MEDLINE, Embase, Scopus, and Web of Science by the end of 2022. Two independent researchers included the articles based on the inclusion and exclusion criteria. A standardized mean difference was calculated for each data and they were pooled to calculate an overall effect size. To assess the heterogeneity between studies, I2 and chi-square tests were utilized. In the case of heterogeneity, meta-regression was performed to identify the potential source.
RESULTS
Fifteen preclinical studies were included. Meta-analysis demonstrated that exercise significantly improves mechanical allodynia (standardized mean difference [SMD], -1.59; 95% confidence interval [CI], -2.16 to -1.02; p < 0.001; I2 = 90.37%), thermal hyperalgesia (SMD, 1.95; 95% CI, 0.96-2.94; p < 0.001), and cold allodynia (SMD, -2.92; 95% CI, -4.4 to -1.43; p < 0.001). The improvement in mechanical allodynia is significantly more in animals with a compression model of SCI (meta-regression coefficient, -1.33; 95% CI, -1.84 to -0.57; p < 0.001) and in mild SCI (p < 0.001). Additionally, the improvement was more prominent if the training was started 7 to 8 days postinjury (coefficient, -2.54; 95% CI, -3.85 to -1.23; p < 0.001) and was continued every day (coefficient, -1.99; 95% CI, -3.07 to -0.9; p < 0.001). Likewise, voluntary exercise demonstrated a significantly more effect size (coefficient, -1.45; 95% CI, -2.67 to -0.23; p = 0.02).
CONCLUSION
Exercise is effective in the amelioration of neuropathic pain. This effect in mechanical allodynia is more prominent if voluntary, continuous training is initiated in the subacute phase of mild SCI.
PubMed: 37798999
DOI: 10.14245/ns.2346588.294 -
Frontiers in Immunology 2023Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of... (Meta-Analysis)
Meta-Analysis Review
The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis.
Pre-clinical evidence shows that neuropathy is associated with complex neuroimmune responses, which in turn are associated with increased intensity and persistence of neuropathic pain. Routine exercise has the potential to mitigate complications of future nerve damage and persistence of pain through neuroimmune regulation. This systematic review aimed to explore the effect of pre-injury exercise on neuroimmune responses, and other physiological and behavioural reactions following peripheral neuropathy in animals. Three electronic databases were searched from inception to July 2022. All controlled animal studies assessing the influence of an active exercise program prior to experimentally-induced traumatic peripheral neuropathy compared to a non-exercise control group on neuroimmune, physiological and behavioural outcomes were selected. The search identified 17,431 records. After screening, 11 articles were included. Meta-analyses showed that pre-injury exercise significantly reduced levels of IL-1β (SMD: -1.06, 95% CI: -1.99 to -0.13, n=40), but not iNOS (SMD: -0.71 95% CI: -1.66 to 0.25, n=82). From 72 comparisons of different neuroimmune outcomes at different anatomical locations, vote counting revealed reductions in 23 pro-inflammatory and increases in 6 anti-inflammatory neuroimmune outcomes. For physiological outcomes, meta-analyses revealed that pre-injury exercise improved one out of six nerve morphometric related outcomes (G-ratio; SMD: 1.95, 95%CI: 0.77 to 3.12, n=20) and one out of two muscle morphometric outcomes (muscle fibre cross-sectional area; SMD: 0.91, 95%CI: 0.27 to 1.54, n=48). For behavioural outcomes, mechanical allodynia was significantly less in the pre-injury exercise group (SMD -1.24, 95%CI: -1.87 to -0.61) whereas no overall effect was seen for sciatic function index. subgroup analysis suggests that timing of outcome measurement may influence the effect of pre-injury exercise on mechanical allodynia. Risk of bias was unclear in most studies, as the design and conduct of the included experiments were poorly reported. Preventative exercise may have potential neuroprotective and immunoregulatory effects limiting the sequalae of nerve injury, but more research in this field is urgently needed.
Topics: Animals; Hyperalgesia; Exercise; Neuralgia
PubMed: 37767095
DOI: 10.3389/fimmu.2023.1215566 -
Brain Research Bulletin Oct 2023Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis... (Review)
Review
Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis in in vivo studies has evolved from simple observations carried out by a trained operator to computerised systems with machine learning that allow the quantification of any variable of interest and the establishment of algorithms for behavioural classification. However, there is not a consensus on gait analysis use in CIPN animal models; therefore, we carried out a systematic review. Of 987 potentially relevant studies, 14 were included, in which different methods were analysed (observation, footprint and CatWalk™). We presented the state-of-the-art of possible approaches to analyse sensory ataxia in rodent models, addressing advantages and disadvantages of different methods available. Semi-automated methods may be of interest when preventive or therapeutic strategies are evaluated, also considering their methodological simplicity and automaticity; up to now, only CatWalk™ analysis has been tested. Future studies should expect that CIPN-affected animals tend to reduce hind paw support due to pain, allodynia or loss of sensation, and an increase in swing phase could or should be observed. Few available studies documented these impairments at the last time point, and only appeared later on respect to other earlier signs of CIPN (such as altered neurophysiological findings). For that reason, gait impairment could be interpreted as late repercussions of loss of sensory.
Topics: Animals; Peripheral Nervous System Diseases; Gait Analysis; Rodentia; Neurotoxicity Syndromes; Antineoplastic Agents; Ataxia
PubMed: 37748696
DOI: 10.1016/j.brainresbull.2023.110769 -
The Korean Journal of Pain Oct 2023: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical...
BACKGROUND
: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain.
METHODS
: Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, I and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source.
RESULTS
: Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; < 0.0001; I = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; < 0.0001; I = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; < 0.0001; I = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia ( < 0 .0001).
CONCLUSIONS
: Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.
PubMed: 37732408
DOI: 10.3344/kjp.23161 -
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 -
Frontiers in Pharmacology 2023Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still...
Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
PubMed: 37426819
DOI: 10.3389/fphar.2023.1199794 -
The Journal of Pain Oct 2023This systematic review and meta-analysis investigated the effects of non-pharmacological manipulations on experimentally induced secondary hypersensitivity in pain-free... (Review)
Review
This systematic review and meta-analysis investigated the effects of non-pharmacological manipulations on experimentally induced secondary hypersensitivity in pain-free humans. We investigated the magnitude (change/difference in follow-up ratings from pre-manipulation ratings) of secondary hypersensitivity (primary outcome), and surface area of secondary hypersensitivity (secondary outcome), in 27 studies representing 847 participants. Risk of bias assessment concluded most studies (23 of 27) had an unclear or high risk of performance and detection bias. Further, 2 (of 27) studies had a high risk of measurement bias. Datasets were pooled by the method of manipulation and outcome. The magnitude of secondary hypersensitivity was decreased by diverting attention, anodal transcranial direct current stimulation, or emotional disclosure; increased by directing attention toward the induction site, nicotine deprivation, or negative suggestion; and unaffected by cathodal transcranial direct current stimulation or thermal change. Area of secondary hypersensitivity was decreased by anodal transcranial direct current stimulation, emotional disclosure, cognitive behavioral therapy, hyperbaric oxygen therapy, placebo analgesia, or spinal manipulation; increased by directing attention to the induction site, nicotine deprivation, or sleep disruption (in males only); and unaffected by cathodal transcranial direct current stimulation, thermal change, acupuncture, or electroacupuncture. Meta-analytical pooling was only appropriate for studies that used transcranial direct current stimulation or hyperbaric oxygen therapy, given the high clinical heterogeneity among the studies and unavailability of data. The evidence base for this question remains small. We discuss opportunities to improve methodological rigor including manipulation checks, structured blinding strategies, control conditions or time points, and public sharing of raw data. PERSPECTIVE: We described the effects of several non-pharmacological manipulations on experimentally induced secondary hypersensitivity in humans. By shedding light on the potential for non-pharmacological therapies to influence secondary hypersensitivity, it provides a foundation for the development and testing of targeted therapies for secondary hypersensitivity.
PubMed: 37356604
DOI: 10.1016/j.jpain.2023.06.013