Pain
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Randomized Controlled Trial Multicenter Study
Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study.
Phase 2a of the PUCCINI study was a placebo-controlled, double-blind, parallel-group, multicenter, proof-of-concept study evaluating the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with diabetic neuropathic pain (DNP) ( ClinicalTrials.gov NCT04641273). Adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain were enrolled and randomized 1:1 to 150 mg oral eliapixant twice daily or placebo for 8 weeks. The primary endpoint was change from baseline in weekly mean 24-hour average pain intensity score at week 8. ⋯ As the primary endpoint was not met, the PUCCINI study was terminated after completion of phase 2a and did not proceed to phase 2b. In conclusion, selective P2X3 antagonism in patients with DNP did not translate to any relevant improvement in different pain intensity outcomes compared with placebo. Funding: Bayer AG.
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Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that contribute to these effects could help in the development of strategies for optimizing treatment of chronic pain conditions. We systematically reviewed and meta-analyzed the literature on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning (OL). ⋯ Overall, the meta-analysis demonstrates that OL can shape placebo hypoalgesia and nocebo hyperalgesia. More research is needed to identify predictors of these effects and to study them in clinical populations. In the future, OL could be an important tool to help maximize placebo hypoalgesia in clinical settings.
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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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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 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.
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Randomized Controlled Trial
The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: a large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL).
A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL-Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. ⋯ There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U. S. adults.