KAPPA-OPIOID RECEPTORS PARTICIPATE IN NERVE GROWTH FACTOR-INDUCED HYPERALGESIA

It has recently been observed that nerve growth factor induces the rap id onset of thermal hyperalgesia, and the more delayed onset of mechan ical hyperalgesia when administered to mature rats. Though several mec hanisms have been proposed to explain this phenomenon, it is still not well understood. Previous studies have shown that nerve growth factor can directly excite nociceptive sensory ganglion neurons in culture v ia activation of kappa excitatory opioid receptors. The possible invol vement of these excitatory opioid receptors in mediating the hyperalge sia was investigated. Nerve growth factor-induced thermal hyperalgesia in rodents was prevented by co-administration of the non-selective op iate antagonist naloxone, as well as by the kappa-selective antagonist nor-binaltorphimine. Addition of the long-acting opioid antagonist, n altrexone, partially prevented mechanical hyperalgesia. Administration of low dose dynorphin to mice (a selective kappa-receptor agonist) mi micked the hyperalgesic effects of nerve growth factor. Opiate antagon ists and anti-nerve growth factor antibody both interfered with Freund 's adjuvant-induced inflammatory hyperalgesia. Altogether, these obser vations suggest that activation of excitatory opioid receptors plays a role in mediating nerve growth factor-induced hyperalgesia and that, in turn, nerve growth factor contributes to the hyperalgesia associate d with inflammatory states. Since opioid receptor antagonists are well tolerated clinically, they may be useful for patients receiving nerve growth factor as part of ongoing trials of the factor in peripheral n europathy.