Pain
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Review Meta Analysis
Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies.
This review examines evidence for the effectiveness of cannabinoids in chronic noncancer pain (CNCP) and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL, and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. ⋯ Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP.
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Review
Targeting Toll-like Receptor-4 (TLR4) - Emerging Therapeutic Target for Persistent Pain States.
Toll-like receptors (TLRs) are a family of pattern recognition receptors that initiate signaling in innate and adaptive immune pathways. The highly conserved family of transmembrane proteins comprises an extracellular domain that recognizes exogenous and endogenous danger molecules and an ectodomain that activates downstream pathways in response. Recent studies suggest that continuous activation or dysregulation of TLR signaling may contribute to chronic disease states. ⋯ Procedures blocking TLR functionality have shown pronounced effects on pain behavior otherwise observed in models of chronic inflammation and nerve injury. This review addresses the role of TLR4 as an emerging therapeutic target for the evolution of persistent pain and its role in noncanonical signaling, mediating anomalous pro-algesic actions of opiates. Accordingly, molecules targeting inhibition of this receptor have promise as disease-modifying and opioid-sparing alternatives for persistent pain states.
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Review
Pressure-induced referred pain areas are more expansive in individuals with a recovered fracture.
Musculoskeletal trauma and pain can sensitize central pain mechanisms, but whether these normalize on recovery is unknown. This study compared the extent of pain referral in individuals recovered from a musculoskeletal trauma and healthy controls. Twenty pain-free participants recovered from a shoulder fracture and 20 age-/sex-matched controls participated in 2 experimental sessions (day-0 and day-1) separated by 24 hours. ⋯ An expansion of pressure-induced pain referral was found in both groups following the DOMS protocol on day-1 (P = 0.05) with a relatively larger expansion (P = 0.05) and higher frequency of pain in the shoulder (P = 0.04) in the recovered pain group. After complete recovery and absence of pain symptoms after a fracture, central pain mechanisms seem to normalize in the region of the trauma after recovery but when sensitized a heightened response can emerge. Such mechanisms could be important for recurrence of pain conditions.
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The translational potential of analgesic approaches emerging from basic research can be augmented by client-owned dog trials. We report on a peripheral interventional approach that uses intra-articular injection of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) to produce a selective long-term chemoinactivation of nociceptive primary afferent nerve endings for pain control in naturally occurring canine osteoarthritis. A single injection of 10 µg of RTX, produced suppression of pain, improvement in gait, weight bearing, and improvement in the dog's activities of daily living lasting 4 months or longer. ⋯ Some targets for analgesia are highly conserved both in protein sequence and level of expression within a target tissue while others diverge substantially from the human. This knowledge is especially important for development of analgesics aimed at peripheral molecular targets and provides a template for informed translational research. The peripheral site of action, long duration of analgesia, apparent safety, and retention of coordination, all resulting from a single dose suggest that intra-articular RTX may be an effective intervention for osteoarthritis pain with few or no side effects and lead to an improved quality of life.