Metabolism: clinical and experimental
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Therapeutic management of chronic pain has not been widely successful owing to a lack of understanding of factors that initiate and maintain the chronic pain condition. Efforts to delineate the mechanisms underlying pain long have focused on neuronal elements of pain pathways, and both opiate- and non-opiate-based therapeutics are thought largely to target neurons. Abnormal neuronal activity at the level of spinal cord "pain centers" in the dorsal horn leads to hypersensitivity or a hyperalgesic response subsequent to the initial painful stimulus. ⋯ Recent evidence even suggests that opioid tolerance and withdrawal hyperalgesia may be initiated and maintained via actions of microglia and astroglia. Together, these recent findings suggest that glia will serve as novel therapeutic targets for the treatment of chronic pain. To fully exploit glia as novel therapeutic targets will require a greater understanding of glial biology, as well as the identification of agents able to control the glial reactions involved in chronic pain, without interfering with beneficial glial functions.
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Pain is an integral part of the defense mechanisms required for survival. Several hereditary syndromes of complete or almost complete insensitivity to pain have been identified and include channelopathy-associated pain insensitivity, of which the most likely candidate gene is the α-subunit of the voltage-gated sodium channel known as Na(v)1.7. Five hereditary sensory and autonomic neuropathy syndromes have been described. ⋯ Most current knowledge on the genetic regulation of pain has been derived from animal models developed mainly in mice. Genomics has the potential to contribute to therapeutic advances with the promising approach of using small interfering RNA in the control of neuropathic pain. Knowledge of the genetic factors that affect opioid efficacy, metabolism, and adverse effects has the potential for personalizing both acute and chronic pain management, and for designing more useful opiate pain medications with lower adverse event profiles.