Advances in pharmacology
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Two decades have passed since the peptide, nociceptin/orphanin FQ (N/OFQ), and its cognate (NOP) receptor were discovered. Although NOP receptor activation causes a similar pattern of intracellular actions as mu-opioid (MOP) receptors, NOP receptor-mediated pain modulation in rodents are more complicated than MOP receptor activation. This review highlights the functional evidence of spinal, supraspinal, and systemic actions of NOP receptor agonists for regulating pain. ⋯ Depending upon their intrinsic efficacies for activating NOP and MOP receptors, bifunctional NOP/MOP receptor agonists warrant additional investigation in primates regarding their side effect profiles. Nevertheless, NOP receptor-related agonists display a much wider therapeutic window as compared to that of MOP receptor agonists in primates. Both selective NOP receptor agonists and bifunctional NOP/MOP receptor agonists hold great potential as effective and safe analgesics without typical opioid-associated side effects in humans.
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Advances in pharmacology · Jan 2016
ReviewSodium Channels in Pain and Cancer: New Therapeutic Opportunities.
Voltage-gated sodium channels (VGSCs) underpin electrical activity in the nervous system through action potential propagation. First predicted by the modeling studies of Hodgkin and Huxley, they were subsequently identified at the molecular level by groups led by Catterall and Numa. VGSC dysfunction has long been linked to neuronal and cardiac disorders with some nonselective sodium channel blockers in current use in the clinic. ⋯ Four channels are potential targets for pain disorders. This conclusion comes from mouse knockout studies and human mutations that prove the involvement of Nav1.3, Nav1.7, Nav1.8, and Nav1.9 in the development and maintenance of acute and chronic pain. In this chapter, we present a short overview of the possible role of Nav1.3, Nav1.7, Nav1.8, and Nav1.9 in human pain and the emerging and unexpected role of sodium channels in cancer pathogenesis.