Articles: hyperalgesia.
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Neuropathic pain is a common side-effect of chemotherapy. Although precise mechanisms are unclear, oxidative stress and mitochondrial damage are involved. We investigated whether the mitochondria targeted antioxidant, MitoVitE, provided better protection against paclitaxel-induced mitochondrial damage in rat dorsal root ganglion (DRG) cells, than a non-targeted form of vitamin E, Trolox. We also determined whether MitoVitE, compared with duloxetine, could limit paclitaxel-induced mechanical hypersensitivity in rats. ⋯ Paclitaxel affected mitochondrial function and glutathione in DRG cells, which was abrogated by MitoVitE but not Trolox, without decreasing cancer cell cytotoxicity. In rats, paclitaxel-induced mechanical hypersensitivity was ameliorated by MitoVitE treatment to an extent similar to duloxetine. These data confirm mitochondria as a mechanistic target for paclitaxel-induced damage and suggest mitochondria targeted antioxidants as future therapeutic strategies.
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Centhaquin has been shown to produce antinociception in the mouse hot plate and tail flick assays through the opioid, the α2A and α2B adrenoceptors. Present study was conducted to determine the effects of centhaquin in a rat model of postoperative pain. Involvement of opioid, and adrenergic receptors was assessed by pretreating rats with antagonists at the opioid (naloxone), α2-(atipamezole) or α2B-(imiloxan) adrenergic receptors. ⋯ This is the first report demonstrating centhaquin antinociception in the rat postoperative pain model. Opioid, α2 adrenergic, and particularly α2B adrenergic receptors are involved in mediating antihyperalgesia while attenuation of nonevoked guarding is mediated by α2B/α2 adrenergic receptors. Centhaquin could be an effective non-sedating alternative in treating postoperative pain in ambulatory surgeries.
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Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. This study assessed CPM to evoked thermal pain in 140 youth (ages 10-17), 63 of whom had FAP and 77 of whom were healthy controls. ⋯ Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in youth with FAP were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth.
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Peripheral nerve injury-induced gene alterations in the dorsal root ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis. Histone methylation gates gene expression. Whether the suppressor of variegation 3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury-induced nociceptive hypersensitivity is unknown. ⋯ The findings of this study suggest that SUV39H1 contributes to nerve injury-induced allodynia and hyperalgesia through gating MOR expression in the injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of nerve injury-induced nociceptive hypersensitivity.
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Preclinical drug discovery for the treatment of chronic pain is at present challenged by the difficulty to study behaviours comparable to the complex human pain experience in animals. Several reports have demonstrated a frequent association of chronic pain in humans with affective disorders, such as anxiety and depression, and impaired cognitive functions, including memory and decision making, and motivation for goal-directed behaviours. In this study, we validated different behavioural outcomes to measure the emotional and cognitive manifestations of neuropathic pain induced in mice by partial sciatic nerve ligation. ⋯ These results indicate that some emotional manifestations of chronic pain do not necessarily resolve when pain is relieved and underline the relevance to evaluate multiple behavioural responses associated with chronic pain, including the affective-motivational and cognitive behaviours, to increase the predictive value of preclinical drug discovery. WHAT DOES THIS STUDY ADD?: In this study, we have validated different behavioural outcomes allowing a reliable measurement of the emotional and cognitive manifestations of neuropathic pain induced in mice by partial sciatic nerve ligation. These results underline the relevance to evaluate these multiple pain-related alterations to improve the predictive value of preclinical drug discovery.