Pain
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Chronic pain associated with osteoarthritis (OA) remains an intractable problem with few effective treatment options. New approaches are needed to model the disease biology and to drive discovery of therapeutics. We present an in vitro model of OA pain, where dorsal root ganglion (DRG) sensory neurons were sensitized by a defined mixture of disease-relevant inflammatory mediators, here called Sensitizing PAin Reagent Composition or SPARC. ⋯ We screened ∼3000 approved drugs and mechanistically focused compounds, yielding data from over 1.2 million individual neurons with detailed assessment of functional OA-SPARC phenotype rescue and orthogonal "off-target" effects. Analysis of confirmed hits revealed diverse potential analgesic mechanisms including ion channel modulators and other mechanisms including MEK inhibitors and tyrosine kinase modulators. Our results suggest that the Raf-MEK-ERK axis in DRG neurons may integrate the inputs from multiple upstream inflammatory mediators found in osteoarthritis patient joints, and MAPK pathway activation in DRG neurons may contribute to chronic pain in patients with osteoarthritis.
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Randomized Controlled Trial Multicenter Study
Comparison of the analgesic effects of "superficial" and "deep" repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study.
We directly compared the analgesic effects of "superficial" and 'deep" repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham "superficial" (using a figure-of-8 [F8]-coil) or "deep" (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. ⋯ The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated ( r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, "deep" and "superficial" rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.
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Meta Analysis
The effect of experimental emotion induction on experimental pain: a systematic review and meta-analysis.
The idea that emotions can influence pain is generally recognized. However, a synthesis of the numerous individual experimental studies on this subject is lacking. The aim of the present systematic review and meta-analysis was to synthesize the existing evidence on the effect of experimental emotion induction on experimental pain in nonclinical adults. ⋯ Taken together, the findings indicate a pain-attenuating effect of positive emotion induction, while the findings for negative emotion induction are less clear. The findings are discussed with reference to theoretical work emphasizing the role of motivational systems and distraction for pain. Limitations include considerable heterogeneity across studies limiting the generalizability of the findings.
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Procedural anxiety and pain negatively affect surgical outcomes and the patient experience during awake, invasive procedures (AIPs). This systematic review aims to evaluate the effect of using virtual reality (VR) to enhance the intraprocedural patient experience during AIPs. PRISMA, Cochrane, and SWiM Reporting Items guidelines were followed. ⋯ No significant differences in patient experience were identified between the "incision" and "endoscopic" subgroups. This review demonstrates that VR can feasibly be used to enhance the patient experience during AIPs by attenuating subjective perceptions of procedural anxiety and pain. However, further RCTs are required to elucidate the effect of VR on more objective measures of the patient experience.