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

The heptadecapeptide, orphanin FQ/nociceptin (OFQ/N), binds with high affinity to the ORL-1/KOR-3 opioid receptor clone, yet binds poorly with traditional opioid receptors. OFQ/N has a complex functional profile with relation to nociceptive processing, displaying pro-nociceptive properties in some studies, acting as an inhibitor of stress-induced analgesia in others, yet producing both spinal and supraspinal antinociceptive actions in other studies. 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 both antinociceptive and stress-related responses. Therefore, the present study assessed whether microinjections into the amygdala of equimolar doses of OFQ/N_1–17 or its shorter-chained active fragments, OFQ/N_1–11 or OFQ/N_1–7, would produce analgesia as measured by either reactivity to high-intensity radiant heat or reactivity to electric shock, and produce hyperalgesia as measured by reactivity to lower-intensity radiant heat. OFQ/N_1–17 in the amygdala produced a dose-dependent and time-dependent increase in high-intensity 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/N_1–11 and OFQ/N_1–7 in the amygdala displayed lower magnitudes of analgesia than OFQ/N_1–17 on this measure, with OFQ/N_1–11 displaying maximal effects at higher (15–30 nmol) doses and OFQ/N_1–7 displaying maximal effects at lower (0.15–1.5 nmol) doses. In contrast to traditional μ and κ opioids and β-endorphin, none of the OFQ/N fragments in the amygdala exhibited any analgesic responses on the jump test. Finally, using a low-intensity radiant heat assay capable of detecting hyperalgesic responses, each of the OFQ/N fragments in the amygdala increased tail-flick latencies on this measure. Therefore, OFQ/N fragments appear to exert only analgesic responses in the amygdala with quantitative and qualitative differences relative to traditional opioid agonists.