Peripheral stimulation of NOP receptors inhibits capsaicin-sensitive afferent neurons in humans and non-human primates

Abstract

Nociceptin, a 17-amino-acid neuropeptide, was originally named because of its pro-nociceptive or hyperalgesic effects in rodent models; however, subsequent studies determined that nociceptin also exerts antinociceptive effects in various paradigms, including capsaicin-induced allodynia. Although nociceptin is known to induce its effects by activating N/OFQ peptide (NOP) receptors (previously known as OP4 or ORL1 receptors), experimental evidence suggests the existence of nociceptin-induced, non-NOP-receptor-mediated nociception-related effects. In addition, it is unknown whether the inhibitory modulation of capsaicin-sensitive neurons by nociceptin can occur in humans. Two recent studies have addressed these issues, and have demonstrated that a therapeutic effect can be achieved by the peripheral modulation of capsaicin-sensitive neurons.