Analgesia elicited by OFQ/nociceptin and its fragments from the amygdala in rats

The heptadecapeptide, orphanin FQ/nociceptin (OFQ/N), binds with high affin ity to the ORL-1/KOR-3 opioid receptor clone. yet binds poorly with traditi onal opioid receptors. OFQ/N has a complex functional profile with relation to nociceptive processing, displaying pro-nociceptive properties in some s tudies, acting as an inhibitor of stress-induced analgesia in others, yet p roducing both spinal and supraspinal antinociceptive actions in other studi es. Among the intracerebral sites at which OFQ/N might produce one or more of these actions is the amygdala which has been intimately implicated in bo th antinociceptive and stress-related responses. Therefore, the present stu dy assessed whether microinjections into the amygdala of equimolar doses of OFQ/N1-17 or its shorter-chained active fragments, OFQ/N1-11 or OFQ/N1-7, would produce analgesia as measured by either reactivity to high-intensity radiant heat or reactivity to electric shock, and produce hyperalgesia as m easured by reactivity to lower-intensity radiant heat. OFQ/N1-17 in the amy gdala produced a dose-dependent and time-dependent increase in high-intensi ty tail-flick latencies with maximal effects observed at a dose range of 0. 75-3 nmol, and lesser effects at lower (0.015-0.15 nmol) and higher (5.5-30 nmol) doses. Both OFQ/N1-11 and OFQ/N1-7 in the amygdala displayed lower m agnitudes of analgesia than OFQ/N1-17 on this measure, with OFQ/N1-11 displ aying maximal effects at higher (15-30 nmol) doses and OFQ/N1-7 displaying maximal effects at lower (0.15-1.5 nmol) doses. In contrast to traditional mu and kappa opioids and beta -endorphin, none of the OFQ/N fragments in th e amygdala exhibited any analgesic responses on the jump test. Finally, usi ng a low-intensity radiant heat assay capable of detecting hyperalgesic res ponses, each of the OFQ/N fragments in the amygdala increased tail-Rick lat encies on this measure. Therefore, OFQ/N fragments appear to exert only ana lgesic responses in the amygdala with quantitative and qualitative differen ces relative to traditional opioid agonists. (C) 2001 Published by Elsevier Science B.V.