Pain
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Mitochondria are present at high concentration at the site of sensory transduction in the peripheral terminals of nociceptors. Because nerve growth factor (NGF), which induces nociceptor sensitization by acting on the high-affinity tropomyosin receptor kinase A (TrkA) receptor, also produces local recruitment of mitochondria in DRG neurons, we evaluated the role of mitochondria in NGF-induced mechanical hyperalgesia. ⋯ Disruption of microtubules, which are required for the trafficking and subcellular localization of mitochondria, also attenuated NGF-induced hyperalgesia. Our results suggest a contribution of mitochondrial localization and function to NGF-dependent pain syndromes.
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In this study, we report that α,β-amyrin, a plant-derived pentacyclic triterpene, reduced persistent inflammatory and neuropathic hyperalgesia in mice by a direct activation of the CB(1) and CB(2) cannabinoid receptors (CB(1)R and CB(2)R). The oral treatment with α,β-amyrin (30 mg/kg) significantly reduced mechanical and thermal hyperalgesia and inflammation induced by complete Freund's adjuvant (CFA) and by partial sciatic nerve ligation (PSNL). The pretreatment with either CB(1)R or CB(2)R antagonists and the knockdown gene of the receptors significantly reverted the antinociceptive effect of α,β-amyrin. ⋯ In addition, α,β-amyrin largely decreased interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), keratinocyte-derived chemokine (KC) and interleukin 6 (IL-6) levels, and myeloperoxidase activity. Likewise, α,β-amyrin prevented the activation of the transcriptional factors: nuclear factor κB (NF-κB) and cyclic adenosine monophosphate response element binding (CREB) and the expression of cyclooxygenase 2 in mice footpads and spinal cords. The present results demonstrated that α,β-amyrin exhibits long-lasting antinociceptive and anti-inflammatory properties in 2 models of persistent nociception via activation of cannabinoid receptors and by inhibiting the production of cytokines and expression of NF-κB, CREB and cyclooxygenase 2.
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Review Meta Analysis
Systematic review of movement-evoked pain versus pain at rest in postsurgical clinical trials and meta-analyses: a fundamental distinction requiring standardized measurement.
To estimate frequency of movement-evoked pain (MEP) measurement in human postsurgical investigations, we reviewed thoracotomy, knee arthroplasty, and hysterectomy clinical trials and meta-analyses. Only 39% of trials measured MEP and 52% failed to identify pain outcome as pain at rest (PAR) or MEP. Temporal trending did not suggest that MEP measurement is becoming more frequent. ⋯ This is an important problem because MEP is usually more severe than PAR; MEP exerts a more direct adverse impact on postsurgical functional recovery and several current and novel pain treatments differentially affect MEP vs PAR. Failure to distinguish between PAR and MEP and standardize their measurement threatens trial precision and ability to identify interventions with the most clinically relevant effects on pain. We therefore recommend developing consistent terminology regarding PAR and MEP, considering inclusion of MEP as a pain outcome in every postsurgical trial, and standardizing measurement of PAR and MEP on a procedure-specific basis.