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 mu and kappa opioids and beta-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.
Shane
R
R
Department of Psychology and Neuropsychology Doctoral Subprogram, Queens College, CUNY, 65-30 Kissena Blvd., Flushing, NY 11367, USA.
Lazar
D A
DA
Rossi
G C
GC
Pasternak
G W
GW
Bodnar
R J
RJ
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004597:Electroshock; D006358:Hot Temperature; D008297:Male; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D000097629:Nociceptin
D018712:Analgesics, Non-Narcotic; D018847:Opioid Peptides; D010446:Peptide Fragments; D000097629:Nociceptin