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International Journal of Molecular... May 2022Currently, myofascial pain has become one of the main problems in healthcare systems. Research into its causes and the structures related to it may help to improve its... (Review)
Review
Currently, myofascial pain has become one of the main problems in healthcare systems. Research into its causes and the structures related to it may help to improve its management. Until some years ago, all the studies were focused on muscle alterations, as trigger points, but recently, fasciae are starting to be considered a new, possible source of pain. This systematic review has been conducted for the purpose of analyze the current evidence of the muscular/deep fasciae innervation from a histological and/or immunohistochemical point of view. A literature search published between 2000 and 2021 was made in PubMed and Google Scholar. Search terms included a combination of fascia, innervation, immunohistochemical, and different immunohistochemical markers. Of the 23 total studies included in the review, five studies were performed in rats, four in mice, two in horses, ten in humans, and two in both humans and rats. There were a great variety of immunohistochemical markers used to detect the innervation of the fasciae; the most used were Protein Gene Marker 9.5 (used in twelve studies), Calcitonin Gene-Related Peptide (ten studies), S100 (ten studies), substance P (seven studies), and tyrosine hydroxylase (six studies). Various areas have been studied, with the thoracolumbar fascia being the most observed. Besides, the papers highlighted diversity in the density and type of innervation in the various fasciae, going from free nerve endings to Pacini and Ruffini corpuscles. Finally, it has been observed that the innervation is increased in the pathological fasciae. From this review, it is evident that fasciae are well innerved, their innervation have a particular distribution and precise localization and is composed especially by proprioceptors and nociceptors, the latter being more numerous in pathological situations. This could contribute to a better comprehension and management of pain.
Topics: Animals; Fascia; Horses; Mechanoreceptors; Mice; Musculoskeletal Physiological Phenomena; Pain; Rats; Sensory Receptor Cells
PubMed: 35628484
DOI: 10.3390/ijms23105674 -
European Spine Journal : Official... Nov 2016Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic... (Review)
Review
PURPOSE
Low back pain (LBP) is the most disabling condition worldwide. Although LBP relates to different spinal pathologies, vertebral bone marrow lesions visualized as Modic changes on MRI have a high specificity for discogenic LBP. This review summarizes the pathobiology of Modic changes and suggests a disease model.
METHODS
Non-systematic literature review.
RESULTS
Chemical and mechanical stimulation of nociceptors adjacent to damaged endplates are likely a source of pain. Modic changes are adjacent to a degenerated intervertebral disc and have three generally interconvertible types suggesting that the different Modic change types represent different stages of the same pathological process, which is characterized by inflammation, high bone turnover, and fibrosis. A disease model is suggested where disc/endplate damage and the persistence of an inflammatory stimulus (i.e., occult discitis or autoimmune response against disc material) create predisposing conditions. The risk to develop Modic changes likely depends on the inflammatory potential of the disc and the capacity of the bone marrow to respond to it. Bone marrow lesions in osteoarthritic knee joints share many characteristics with Modic changes adjacent to degenerated discs and suggest that damage-associated molecular patterns and marrow fat metabolism are important pathogenetic factors. There is no consensus on the ideal therapy. Non-surgical treatment approaches including intradiscal steroid injections, anti-TNF-α antibody, antibiotics, and bisphosphonates have some demonstrated efficacy in mostly non-replicated clinical studies in reducing Modic changes in the short term, but with unknown long-term benefits. New diagnostic tools and animal models are required to improve painful Modic change identification and classification, and to clarify the pathogenesis.
CONCLUSION
Modic changes are likely to be more than just a coincidental imaging finding in LBP patients and rather represent an underlying pathology that should be a target for therapy.
Topics: Bone Marrow; Humans; Intervertebral Disc; Low Back Pain; Lumbar Vertebrae; Magnetic Resonance Imaging; Models, Biological
PubMed: 26914098
DOI: 10.1007/s00586-016-4459-7 -
The Cochrane Database of Systematic... Jan 2017This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin are used to treat peripheral neuropathic pain. Following application to the skin, capsaicin causes enhanced sensitivity, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation. High-concentration (8%) capsaicin patches were developed to increase the amount of capsaicin delivered; rapid delivery was thought to improve tolerability because cutaneous nociceptors are 'defunctionalised' quickly. The single application avoids noncompliance. Only the 8% patch formulation of capsaicin is available, with a capsaicin concentration about 100 times greater than conventional creams. High-concentration topical capsaicin is given as a single patch application to the affected part. It must be applied under highly controlled conditions, often following local anaesthetic, due to the initial intense burning sensation it causes. The benefits are expected to last for about 12 weeks, when another application might be made.
OBJECTIVES
To review the evidence from controlled trials on the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in chronic neuropathic pain in adults.
SEARCH METHODS
For this update, we searched CENTRAL, MEDLINE, Embase, two clinical trials registries, and a pharmaceutical company's website to 10 June 2016.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled studies of at least 6 weeks' duration, using high-concentration (5% or more) topical capsaicin to treat neuropathic pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.Efficacy outcomes reflecting long-duration pain relief after a single drug application were from the Patient Global Impression of Change (PGIC) at specific points, usually 8 and 12 weeks. We also assessed average pain scores over weeks 2 to 8 and 2 to 12 and the number of participants with pain intensity reduction of at least 30% or at least 50% over baseline, and information on adverse events and withdrawals.We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We included eight studies, involving 2488 participants, two more studies and 415 more participants than the previous version of this review. Studies were of generally good methodological quality; we judged only one study at high risk of bias, due to small size. Two studies used a placebo control and six used 0.04% topical capsaicin as an 'active' placebo to help maintain blinding. Efficacy outcomes were inconsistently reported, resulting in analyses for most outcomes being based on less than complete data.For postherpetic neuralgia, we found four studies (1272 participants). At both 8 and 12 weeks about 10% more participants reported themselves much or very much improved with high-concentration capsaicin than with 'active' placebo, with point estimates of numbers needed to treat for an additional beneficial outcome (NNTs) of 8.8 (95% confidence interval (CI) 5.3 to 26) with high-concentration capsaicin and 7.0 (95% CI 4.6 to 15) with 'active' placebo (2 studies, 571 participants; moderate quality evidence). More participants (about 10%) had average 2 to 8-week and 2 to 12-week pain intensity reductions over baseline of at least 30% and at least 50% with capsaicin than control, with NNT values between 10 and 12 (2 to 4 studies, 571 to 1272 participants; very low quality evidence).For painful HIV-neuropathy, we found two studies (801 participants). One study reported the proportion of participants who were much or very much improved at 12 weeks (27% with high-concentration capsaicin and 10% with 'active' placebo). For both studies, more participants (about 10%) had average 2 to 12-week pain intensity reductions over baseline of at least 30% with capsaicin than control, with an NNT of 11 (very low quality evidence).For peripheral diabetic neuropathy, we found one study (369 participants). It reported about 10% more participants who were much or very much improved at 8 and 12 weeks. One small study of 46 participants with persistent pain following inguinal herniorrhaphy did not show a difference between capsaicin and placebo for pain reduction (very low quality evidence).We downgraded the quality of the evidence for efficacy outcomes by one to three levels due to sparse data, imprecision, possible effects of imputation methods, and susceptibility to publication bias.Local adverse events were common, but not consistently reported. Serious adverse events were no more common with active treatment (3.5%) than control (3.2%). Adverse event withdrawals did not differ between groups, but lack of efficacy withdrawals were somewhat more common with control than active treatment, based on small numbers of events (six to eight studies, 21 to 67 events; moderate quality evidence, downgraded due to few events). No deaths were judged to be related to study medication.
AUTHORS' CONCLUSIONS
High-concentration topical capsaicin used to treat postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy generated more participants with moderate or substantial levels of pain relief than control treatment using a much lower concentration of capsaicin. These results should be interpreted with caution as the quality of the evidence was moderate or very low. The additional proportion who benefited over control was not large, but for those who did obtain high levels of pain relief, there were usually additional improvements in sleep, fatigue, depression, and quality of life. High-concentration topical capsaicin is similar in its effects to other therapies for chronic pain.
Topics: Administration, Topical; Adult; Analgesics; Capsaicin; Chronic Pain; Diabetic Neuropathies; HIV Infections; Humans; Neuralgia; Neuralgia, Postherpetic; Numbers Needed To Treat; Ointments; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 28085183
DOI: 10.1002/14651858.CD007393.pub4 -
Journal of Dairy Science Nov 2022The objectives of this systematic review were to investigate the association between nonsteroidal anti-inflammatory drug (NSAID) use during the treatment of claw horn...
Graduate Student Literature Review: A systematic review on the associations between nonsteroidal anti-inflammatory drug use at the time of diagnosis and treatment of claw horn lameness in dairy cattle and lameness scores, algometer readings, and lying times.
The objectives of this systematic review were to investigate the association between nonsteroidal anti-inflammatory drug (NSAID) use during the treatment of claw horn lameness in dairy cattle and locomotion score (LS), nociceptive threshold, and lying times. A total of 229 studies were initially identified and had their title and abstract screened. From this, we screened the full text of 23 articles, identifying 6 articles for inclusion in the systematic review. Of these 6, 5 reported LS, 2 reported nociceptor thresholds, and 1 reported lying times. The quality of evidence was assessed using a Cochrane risk-of-bias tool and CONSORT items reported for each included study. Due to heterogeneity between the studies, data were reported following Cochrane's Synthesis without meta-analysis guidelines. Identified heterogeneity between the studies included differences in LS systems and statistical analyses, length of time from enrollment to outcome reported, the NSAID used, concomitant treatments administered, and severity and chronicity of lameness. Recommendations are made with respect to consistency of LS reporting and analysis, along with improvements that may be noted with compulsory reporting guidelines. There were at least some concerns over the risk of bias in 4 of the studies, with risks of bias present in missing outcome data between the study groups. Within the 5 studies included with LS outcomes, there were 22 different pairwise comparisons with either NSAID or NSAID + block as the intervention, with measures of association with presence or absence of lameness as the outcome available for 20 of these comparisons. Animals in the NSAID intervention groups had a lower point estimate lameness risk than animals in the comparison groups in 3 of 8 and 9 of 14 analyses for LS outcomes <10 and ≥10 d post-treatment, respectively. However, there was no difference identified between animals in the NSAID intervention groups compared with the animals in the control group in any of these pairwise comparisons with lameness as the outcome. Twelve pairwise comparisons were reported in the 2 studies with nociceptor threshold as an outcome. Animals in the NSAID intervention groups had a greater nociceptor threshold point estimate compared with animals in the comparison groups in 6 of 6 and 1 of 6 analyses for outcomes <10 and ≥10 d post-treatment, respectively. However, no differences were identified between animals in the NSAID intervention groups and those in the comparison groups. All 4 pairwise comparisons reported in the study with lying times as an outcome found no differences between animals in the NSAID groups and those in the comparison groups. Despite the widespread use of NSAID in the treatment of claw horn lameness, there is a lack of studies of NSAID association with LS, nociceptive thresholds, or lying times. The limited evidence is consistent with no association with NSAID use and those parameters, but comparability across studies was limited by heterogeneity.
Topics: Cattle; Animals; Humans; Lameness, Animal; Hoof and Claw; Cattle Diseases; Anti-Inflammatory Agents, Non-Steroidal; Students
PubMed: 36114054
DOI: 10.3168/jds.2022-22127 -
British Medical Bulletin Jun 2023Chronic low back pain, common from the sixth decade, negatively impacts the quality of life of patients and health care systems. Recently, mesenchymal stem cells (MSCs)...
BACKGROUND
Chronic low back pain, common from the sixth decade, negatively impacts the quality of life of patients and health care systems. Recently, mesenchymal stem cells (MSCs) have been introduced in the management of degenerative discogenic pain. The present study summarizes the current knowledge on the effectiveness of MSCs in patients with discogenic back pain.
SOURCES OF DATA
We performed a systematic review of the literature following the PRISMA guidelines. We searched PubMed and Google Scholar database, and identified 14 articles about management of chronic low back pain with MSCs injection therapy. We recorded information on type of stem cells employed, culture medium, clinical scores and MRI outcomes.
AREAS OF AGREEMENT
We identified a total of 303 patients. Ten studies used bone marrow stem cells. In the other four studies, different stem cells were used (of adipose, umbilical, or chondrocytic origin and a pre-packaged product). The most commonly used scores were Visual Analogue Scale and Oswestry Disability Index.
AREAS OF CONTROVERSY
There are few studies with many missing data.
GROWING POINTS
The studies analysed demonstrate that intradiscal injections of MSCs are effective on discogenic low-back pain. This effect may result from inhibition of nociceptors, reduction of catabolism and repair of injured or degenerated tissues.
AREAS TIMELY FOR DEVELOPING RESEARCH
Further research should define the most effective procedure, trying to standardize a single method.
Topics: Humans; Low Back Pain; Quality of Life; Treatment Outcome; Mesenchymal Stem Cells; Magnetic Resonance Imaging
PubMed: 37164906
DOI: 10.1093/bmb/ldad008 -
Scandinavian Journal of Pain Oct 2021The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial nociceptors is suggested as a potential mechanism and injections of botulinum toxin (BONTA) have thus been used in the treatment for both headache conditions. BONTA inhibits the release of acetylcholine at the neuromuscular junction and inhibits contraction of skeletal muscles. If the pain is precipitated by increased tone in cervical muscles, local injections of BONTA could represent a prophylactic measure. However, the treatment is still controversial, and a thorough assessment of the current evidence is required. This review aims to assess the evidence of BONTA injection as a prophylactic treatment for CTTH and CEH by reviewing and examining the quality of placebo-controlled, randomized trials.
METHODS
Data sources: we searched in the following databases: PubMed (including Medline), Embase, Cochrane Central register of Controlled Trials, Cinahl, Amed, SCOPUS and Google Scholar including other repository sources. Both MeSH and free keywords were used in conducting the systematic search in the databases. The search covered publications from the root of the databases to November 2020.
STUDY ELIGIBILITY CRITERIA
The review included RCTs, comparing single treatment of BONTA with placebo on patients with CTTH or CEH above 18 years of age, by measuring pain severity/relief or headache frequency.
DATA EXTRACTION
The following data were extracted: year of publication, country, setting, trial design, number of participants, injection procedure, BONTA dosages, and clinical outcome measures.
STUDY APPRAISAL
To assess validity and quality, and risk of bias, the Oxford Pain Validity Scale, Modified Jadad Scale, last version of Cochrane Collaboration's tool for assessing risk of bias (RoB 2), and the CONSORT 2010 Checklist were used. The trials were assessed, and quality scored independently by two of the reviewers. A quantitative synthesis and meta-analyses of headache frequency and intensity were performed.
RESULTS
We extracted 16 trials, 12 on prophylactic BONTA treatment for CTTH and four on CEH. Of these 12 trials (8 on CTTH and 4 on CEH) were included in the quantitative synthesis. A majority of the trials found no significant difference on the primary outcome measure when BONTA treatment was compared with placebo. Three "positive" trials, reporting significant difference in favor of BONTA treatment, but two of these were hampered by low validity and quality scores and high risk of bias.
CONCLUSIONS
There is no clear clinical evidence supporting prophylactic treatment with BONTA for CTTH or CEH.
Topics: Botulinum Toxins, Type A; Headache; Headache Disorders; Humans; Post-Traumatic Headache; Randomized Controlled Trials as Topic; Tension-Type Headache
PubMed: 34090319
DOI: 10.1515/sjpain-2021-0038 -
The Cochrane Database of Systematic... Oct 2013This is an update of the original Cochrane review published in Issue 2, 2007. The cause of postherpetic neuralgia is damage to peripheral neurons, dorsal root ganglia,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original Cochrane review published in Issue 2, 2007. The cause of postherpetic neuralgia is damage to peripheral neurons, dorsal root ganglia, and the dorsal horn of the spinal cord, secondary to herpes zoster infection (shingles). In postherpetic neuralgia, peripheral neurons discharge spontaneously and have lowered activation thresholds, and exhibit an exaggerated response to stimuli. Topical lidocaine dampens peripheral nociceptor sensitisation and central nervous system hyperexcitability, and may benefit patients with postherpetic neuralgia.
OBJECTIVES
To examine efficacy and safety of topical lidocaine in the treatment of postherpetic neuralgia.
SEARCH METHODS
We searched the Cochrane Pain, Palliative and Supportive Care Group Trials Register, CENTRAL, MEDLINE, EMBASE, LILACS, SIGLE, Citation Index, the reference lists of all eligible trials, key textbooks, and previous systematic reviews. Last search conducted April 2011.
SELECTION CRITERIA
Randomised or quasi‐randomised trials comparing topical applications of lidocaine in patients of all ages with postherpetic neuralgia (pain persisting at the site of shingles at least one month after the onset of the acute rash).
DATA COLLECTION AND ANALYSIS
Two review authors extracted data, and a third checked them.
MAIN RESULTS
In the original review three studies involving 182 topical lidocaine treated participants and 132 control participants were included. Two studies gave data on pain relief, and the remaining study provided data on secondary outcome measures. The largest study published as an abstract compared topical lidocaine patch to a placebo patch and accounted for 150 of the 314 participants (48%). A meta‐analysis combining two studies identified a significant difference between topical lidocaine and control groups for the primary outcome measure: a mean improvement in pain relief according to a pain relief scale. Topical lidocaine relieved pain better than placebo (P = 0.003). There was a statistical difference between the groups for the secondary outcome measure of mean VAS score reduction (P = 0.03), but this was only for a single small study. There were a similar number of adverse skin reactions in both treatment and placebo groups. The highest recorded blood lidocaine concentration varied between 59 ng/ml and 431 ng/ml between studies. The latter figure is high and the authors of the study suggest that the sample had been contaminated during the assay procedure.
AUTHORS' CONCLUSIONS
Since the last version of this review in Issue 2, 2007 no new studies have been found and the results therefore remain the same. There is still insufficient evidence to recommend topical lidocaine as a first‐line agent in the treatment of postherpetic neuralgia with allodynia. Further research should be undertaken on the efficacy of topical lidocaine for other chronic neuropathic pain disorders, and also to compare different classes of drugs (e.g. topical anaesthetic applications versus anti‐epileptic drugs).
Topics: Administration, Topical; Anesthetics, Local; Humans; Lidocaine; Neuralgia, Postherpetic
PubMed: 24166584
DOI: 10.1002/14651858.CD004846.pub3 -
Reviews in the Neurosciences May 2017Upregulation of defensive reflexes such as the nociceptive flexion reflex (NFR) has been attributed to sensitisation of peripheral and spinal nociceptors and is often... (Meta-Analysis)
Meta-Analysis Review
Upregulation of defensive reflexes such as the nociceptive flexion reflex (NFR) has been attributed to sensitisation of peripheral and spinal nociceptors and is often considered biomarkers of pain. Experimental modulation of defensive reflexes raises the possibility that they might be better conceptualised as markers of descending cognitive control. Despite strongly held views on both sides and several narrative reviews, there has been no attempt to evaluate the evidence in a systematic manner. We undertook a meta-analytical systematic review of the extant English-language literature from inception. Thirty-six studies satisfied our a priori criteria. Seventeen were included in the meta-analysis. Reflexive threshold was lower in people with clinical pain than it was in pain-free controls, but reflex size, latency, and duration were unaffected. The pattern of difference was not consistent with sensitisation of nociceptive neurones, as these changes were not isolated to the affected body part but was more consistent with top-down cognitive control reflective of heightened protection of body tissue. The pattern of modulation is dependent on potentially complex evaluative mechanisms. We offer recommendations for future investigations and suggest that defensive reflex threshold may reflect a biomarker of a broader psychological construct related to bodily protection, rather than sensitisation of primary nociceptors, spinal nociceptors, or pain.
Topics: Central Nervous System Sensitization; Humans; Nociception; Pain; Perceptual Defense; Reflex; Sensory Thresholds
PubMed: 28475100
DOI: 10.1515/revneuro-2016-0057 -
Pain Physician Sep 2018Epidural injection is performed for treatment of back and radicular pain in patients with lumbosacral disc herniation (LDH). Steroids are usually administered to... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Epidural injection is performed for treatment of back and radicular pain in patients with lumbosacral disc herniation (LDH). Steroids are usually administered to effectively remove inflammatory mediators, and local anesthetics or saline also contribute to pain reduction by washing out chemical mediators or blocking the nociceptor activity. Controversy exists regarding whether steroids produce superior clinical effects compared with local anesthetics or saline.
OBJECTIVES
This study investigated whether epidural injection of steroids produces better clinical effects than local anesthetics or saline in the treatment of LDH.
STUDY DESIGN
A literature search was performed in MEDLINE, EMBASE, Cochrane review, and KoreaMed for studies published from January 1996 until July 2017. From among the studies fulfilling the search criteria, those that compared the clinical efficacy of steroids and control agents, such as local anesthetics or saline, in terms of pain control and functional improvement were included in this study. Exclusion criteria included a previous history of lumbosacral surgery, non-specific low back pain, severe spinal stenosis, and severe disc degeneration.
SETTING
A systematic review and meta-analysis using a random effects model on randomized controlled studies (RCTs).
METHODS
After reviewing titles, abstracts, and full texts of 6,711 studies that were chosen following removal of duplicates after the initial database search, 15 randomized controlled studies were included in our qualitative synthesis. Data including pain score, functional score, and follow-up period were extracted from 14 studies and analyzed using a random effects model to calculate the effect size and its corresponding statistical significance. Quality and level of evidence were established in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
RESULTS
Steroids and local anesthetics were shown to be effective. Steroid showed significantly better pain control than control agents at 1 month, 3 months, and 6 months. The superiority of steroid in pain control was more prominent at one month, but diminished from 3 months to 1 year, showing no significant superiority in terms of mean difference, With respect to functional score, no significant difference was observed between steroids and control agents. The subgroup analysis showed that steroid revealed significant superiority in pain and functional score at 1 month to saline rather than local anesthetics. Generally, the quality of included studies was evaluated as high-grade, but the evidence level was determined to be moderate, due to inconsistencies.
LIMITATION
Analyses of safety or adverse effects could not be performed due to a lack of available data from the included studies.
CONCLUSIONS
Steroid is recommended over local anesthetics or saline for pain control in patients with LDH, with a weak strength of recommendation. The superiority of steroids was remarkable, especially at relatively short-term follow-ups, and maintained until the 1 year follow-up. The clinical benefits of steroids at 1 month were more prominent when compared with saline, than when compared with local anesthetics.
KEY WORDS
Steroid, local anesthetics, saline, epidural injection, pain, function, meta-analysis, systemic review.
Topics: Anesthetics, Local; Humans; Injections, Epidural; Intervertebral Disc Displacement; Low Back Pain; Lumbosacral Region; Pain; Pain Management; Radiculopathy; Steroids; Treatment Outcome
PubMed: 30282390
DOI: No ID Found