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Attempting to Separate Placebo Effects from Exercise in Chronic Pain: A Systematic Review and Meta-analysis.
Miller, CT, Owen, PJ, Than, CA, Ball, J, Sadler, K, Piedimonte, A, Benedetti, F, Belavy, DL
Sports medicine (Auckland, N.Z.). 2022;(4):789-816
Abstract
BACKGROUND Pain is the most disabling characteristic of musculoskeletal disorders, and while exercise is promoted as an important treatment modality for chronic musculoskeletal conditions, the relative contribution of the specific effects of exercise training, placebo effects and non-specific effects such as natural history are not clear. The aim of this systematic review and meta-analysis was to determine the relative contribution of these factors to better understand the true effect of exercise training for reducing pain in chronic primary musculoskeletal pain conditions. DESIGN Systematic review with meta-analysis DATA SOURCES MEDLINE, CINAHL, SPORTDiscus, EMBASE and CENTRAL from inception to February 2021. Reference lists of prior systematic reviews. ELIGIBILITY CRITERIA Randomised controlled trials of interventions that used exercise training compared to placebo, true control or usual care in adults with chronic primary musculoskeletal pain. The review was registered prospectively with PROSPERO (CRD42019141096). RESULTS We identified 79 eligible trials for quantitative analysis. Pairwise meta-analysis showed very low-quality evidence (GRADE criteria) that exercise training was not more effective than placebo (g [95% CI]: 0.94 [- 0.17, 2.06], P = 0.098, I2 = 92.46%, studies: n = 4). Exercise training was more effective than true, no intervention controls (g [95% CI]: 0.99 [0.66, 1.32], P < 0.001, I2 = 92.43%, studies: n = 42), usual care controls (g [95% CI]: 0.64 [0.44, 0.83], P < 0.001, I2 = 76.52%, studies: n = 33), and when all controls combined (g [95% CI]: 0.84 [0.64, 1.04], P < 0.001, I2 = 90.02%, studies: n = 79). CONCLUSIONS There is very low-quality evidence that exercise training is not more effective than non-exercise placebo treatments in chronic pain. Exercise training and the associated clinical encounter are more effective than true control or standard medical care for reductions in pain for adults with chronic musculoskeletal pain, with very low quality of evidence based on GRADE criteria.
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Dual Enkephalinase Inhibitors and Their Role in Chronic Pain Management.
Southerland, WA, Gillis, J, Kuppalli, S, Fonseca, A, Mendelson, A, Horine, SV, Bansal, N, Gulati, A
Current pain and headache reports. 2021;(5):29
Abstract
PURPOSE OF REVIEW Dual enkephalinase inhibitors (DENKIs) are pain medications that indirectly activate opioid receptors and can be used as an alternative to traditional opioids. Understanding the physiology of enkephalins and their inhibitors and the pharmacology of these drugs will allow for proper clinical application for chronic pain patients in the future. RECENT FINDINGS DENKIs can be used as an alternative mode of analgesia for patients suffering from chronic pain by preventing the degradation of endogenous opioid ligands. By inhibiting the two major enkephalin-degrading enzymes (neprilysin and aminopeptidase N), DENKIs can provide analgesia with less adverse effects than nonendogenous opioids. The purpose of this paper is to review the current literature investigating DENKIs and explore their contribution to chronic pain management.
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Anesthesia Related to Breast Cancer Recurrence and Chronic Pain: A Review of Current Research.
Kujawa, E, Blau, A, Rametta, L
AANA journal. 2021;(4):291-298
Abstract
Patients with breast cancer often require several procedures requiring anesthesia, such as central venous catheter placements, mastectomies, lymph node dissections, and reconstructive surgeries. Recent research findings have suggested there may be a reduced risk of cancer recurrence and chronic pain with specific anesthetic techniques. Regional techniques, total intravenous anesthetics, and select adjuncts have been reviewed to identify their role in breast cancer recurrence and chronic pain. A review of the pathophysiology as it pertains to volatile anesthetics, propofol as a total intravenous anesthetic, paravertebral nerve blocks, dexmedetomidine, and ketorolac, as well as the role each of these plays in the prevention of chronic pain and cancer recurrence is provided. Current research and recommendations for practice are presented in the context of providing anesthesia to mitigate chronic pain and cancer recurrence in patients with breast cancer.
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Antispasmodics for Chronic Abdominal Pain: Analysis of North American Treatment Options.
Brenner, DM, Lacy, BE
The American journal of gastroenterology. 2021;(8):1587-1600
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Abstract
Chronic abdominal pain is a common gastrointestinal (GI) symptom that characterizes many functional GI disorders/disorders of gut-brain interaction, including irritable bowel syndrome, functional dyspepsia, and centrally mediated abdominal pain syndrome. The symptoms of abdominal pain in these highly prevalent disorders are often treated with antispasmodic agents. Antispasmodic treatment includes a broad range of therapeutic classes with different mechanisms of action, including anticholinergic/antimuscarinic agents (inhibition of GI smooth muscle contraction), calcium channel inhibitors (inhibition of calcium transport into GI smooth muscle), and direct smooth muscle relaxants (inhibition of sodium and calcium transport). The aim of this review article was to examine the efficacy and safety of antispasmodics available in North America (e.g., alverine, dicyclomine, hyoscine, hyoscyamine, mebeverine, otilonium, pinaverium, and trimebutine) for the treatment of chronic abdominal pain in patients with common disorders of gut-brain interaction. For the agents examined, comparisons of studies are limited by inconsistencies in treatment dosing and duration, patient profiles, and diagnostic criteria employed. Furthermore, variability in study end points limits comparisons. Risk of selection, performance, detection, attrition, and reporting bias also differed among studies, and in many cases, risks were considered "unclear." The antispasmodics evaluated in this review, which differ in geographic availability, were found to vary dramatically in efficacy and safety. Given these caveats, each agent should be considered on an individual basis, rather than prescribed based on information across the broad class of agents.
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Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain.
Stella, B, Baratta, F, Della Pepa, C, Arpicco, S, Gastaldi, D, Dosio, F
Drugs. 2021;(13):1513-1557
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The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients' quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations.
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Quality of life and functional outcomes with tapentadol prolonged release in chronic musculoskeletal pain: post hoc analysis.
Ferri, CM, Natoli, S, Sanz-Ayan, P, Magni, A, Guerrero, C, Lara-Solares, A, Liedgens, H, Thömmes, G, Karra, R
Pain management. 2021;(2):173-187
Abstract
Aims: To investigate quality of life (QOL) and functionality changes in chronic pain during tapentadol prolonged release (PR) treatment. Patients & methods: Post hoc analysis of data from three Phase III trials in patients with osteoarthritis knee pain or low back pain. QOL and functionality changes were assessed by SF-36 scores. Results: All SF-36 subdomain scores improved progressively to week 3 of tapentadol titration and were sustained during 12-week maintenance treatment. Improvements in SF-36 scores were similar between tapentadol dose groups (e.g., 200 to <300 mg vs ≥500 mg), with no greater effect from higher doses. QOL and functionality improvements were consistently greater with tapentadol PR than oxycodone controlled release. Conclusion: Tapentadol PR provides consistent, clinically relevant improvements in QOL and functionality in chronic pain.
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B vitamins as a treatment for diabetic pain and neuropathy.
Karaganis, S, Song, XJ
Journal of clinical pharmacy and therapeutics. 2021;(5):1199-1212
Abstract
WHAT IS KNOWN AND OBJECTIVE B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this review was to summarize the current evidence for the efficacy of B vitamin therapy in diabetic patients with neuropathy. COMMENT We screened the English literature for clinical studies evaluating B vitamins as a therapy for pain and neuropathy in diabetic patients. We selected 43 relevant studies for qualitative analysis based on our selection criteria. Our survey of the literature revealed substantive heterogeneity with respect to efficacies of reported outcomes, as well as study design. Most beneficial outcomes were reported against baseline measures, with few positive comparisons against placebo. This highlights the need for larger, placebo-controlled studies. WHAT IS NEW AND CONCLUSION B vitamins should be considered a plausible therapy for diabetic neuropathy, but its overall efficacy remains uncertain and requires further study.
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Polygenic risk scores indicates genetic overlap between peripheral pain syndromes and chronic postsurgical pain.
van Reij, RRI, Voncken, JW, Joosten, EAJ, van den Hoogen, NJ
Neurogenetics. 2020;(3):205-215
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Chronic postsurgical pain (CPSP) is a debilitating chronic pain condition that has a substantial effect on quality of life. CPSP shows considerable clinical overlap with different chronic peripheral pain syndromes, suggesting a shared aetiology. This study aims to assess the genetic overlap between different chronic pain syndromes and CPSP, providing relevant biological context for potential chronic pain markers of CPSP. To analyse the genetic overlap between CPSP and chronic peripheral pain syndromes, recent GWAS studies were combined for polygenic risk scores (PRS) analysis, using a cohort of CPSP patients as starting point. Biological contextualisation of genetic marker, overlap between CPSP and chronic pain syndromes, was assessed through Gene Ontology (GO), using Pathway Scoring Algorithm (PASCAL) and REVIGO. PRS analyses suggest a significant genetic overlap between CPSP and 3 chronic pain disorders: chronic widespread pain (CWP, p value threshold = 0.003, R2 0.06, p = 0.003), rheumatoid arthritis (RA, p value threshold = 0.0177, R2 = 0.04, p = 0.017) and possibly sciatica (p value threshold = 0.00025, R2 = 0.03, p = 0.045). Whereas no significant genetic overlap was found with cluster headache and migraine, the outcome for osteoarthritis (OA) was inconsistent between the cohorts. This is likely related to cohort composition, as repeated random reallocation of patients' nullified CPSP/OA outcome variation between the discovery and replication cohorts. GO analyses suggested an aetiological involvement of genetic markers that control neurological signalling (specifically sodium channels) and inflammatory response. The current study reaffirms the impact of sample size, cohort composition and open data accessibility on the unbiased identification of genetic overlap across disorders. In conclusion, this study is the first to report genetic overlap between regulatory processes implicated in CPSP and chronic peripheral pain syndromes. Interaction between neurological signalling and inflammatory response may explain the genetic overlap between CPSP, CWP and RA. Enhanced understanding of mechanisms underlying chronification of pain will aid the development of new therapeutic strategies for CPSP with sodium channel biochemistry as a potential candidate.
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Nutritional factors in chronic musculoskeletal pain: unravelling the underlying mechanisms.
Elma, Ö, Yilmaz, ST, Deliens, T, Coppieters, I, Clarys, P, Nijs, J, Malfliet, A
British journal of anaesthesia. 2020;(2):e231-e233
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Chronic pelvic pain syndrome: Highlighting medicinal plants toward biomolecules discovery for upcoming drugs formulation.
Salehi, B, Butnariu, M, Corneanu, M, Sarac, I, Vlaisavljevic, S, Kitic, D, Rahavian, A, Abedi, A, Karkan, MF, Bhatt, ID, et al
Phytotherapy research : PTR. 2020;(4):769-787
Abstract
Chronic pelvic pain syndrome (CPPS) can be triggered by a various types of gynecological, gastrointestinal, urological, and musculoskeletal disorders. Recently, the role of the central nervous system has proven to be an integral part on the development of any chronic pain syndrome, including CPPS. However, owing to the complex and heterogeneous etiology and pathophysiology of CPPS, the establishment of effective therapeutic interventions remains challenging for both physicians and patients. Nonetheless, recent studies have pointed that medicinal plants and their secondary metabolites can be effectively used in CPPS therapy, besides contributing to restore the patients' quality of life and potentiate the conventional CPPS management. In this sense, this review aims to provide a careful overview on the biomedical data for the use of medicinal plants use and their secondary metabolites on CPPS management.