Pain
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Randomized Controlled Trial
Education can reassure people with rotator cuff-related shoulder pain: a 3-arm, randomised, online experiment.
We aimed to investigate the immediate effect of best practice education (with and without pain science messages) and structure-focused education on reassurance among people with rotator cuff-related shoulder pain. We conducted a 3-arm, parallel-group, randomised experiment. People with rotator cuff-related shoulder pain were randomised (1:1:1) to (1) best practice education (highlights that most shoulder pain is not serious or a good indicator of tissue damage and recommends simple self-management strategies); (2) best practice education plus pain science messages (which attempt to improve understanding of pain); and (3) structure-focused education (highlighting that structural changes are responsible for pain and should be targeted with treatment). ⋯ Adding pain science messages to best practice education slightly increased both measures of reassurance (0.2, 95% CI 0.0-0.4). Clinicians treating patients with rotator cuff-related shoulder pain should highlight that most shoulder pain is not serious or a good indicator of tissue damage and recommend simple self-management strategies. The benefit of adding pain science messages is small.
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Virtual reality (VR) has been shown to be effective in pain management. However, to date, little is known about the mechanisms by which immersive experiences influence pain processing. The aim of this study was to investigate the direct effects of an immersive VR environment on the perception of experimental pain in individuals with chronic pain and pain-free controls. ⋯ This applies for participants with chronic pain and pain-free controls. These VR effects exceeded the effects of mental imagery on the nonimmersive control condition. This indicates that VR effectively modulates pain perception in both patients and controls irrespective of differences in pain perception.
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Nociceptor cell bodies generate "spontaneous" discharge that can promote ongoing pain in persistent pain conditions. Little is known about the underlying mechanisms. Recordings from nociceptor cell bodies (somata) dissociated from rodent and human dorsal root ganglia have shown that previous pain in vivo is associated with low-frequency discharge controlled by irregular depolarizing spontaneous fluctuations of membrane potential (DSFs), likely produced by transient inward currents across the somal input resistance. ⋯ Partial reduction of the amplitude or frequency of DSFs by perfusion of pharmacological inhibitors indicated small but significant contributions from Nav1.7, Nav1.8, TRPV1, TRPA1, TRPM4, and N-type Ca 2+ channels. Less specific blockers suggested a contribution from NALCN channels, and global knockout suggested a role for Nav1.9. The combination of high somal input resistance plus background activity of diverse ion channels permeable to Na + or Ca 2+ produces DSFs that are poised to reach AP threshold if resting membrane potential depolarizes, AP threshold decreases, or DSFs become enhanced-all of which can occur under painful neuropathic and inflammatory conditions.
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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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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.