Blockade of μ-opioid receptors reveals the hyperalgesic effect of orphanin FQ/nociceptin in the rat hot plate test

• Orphanin FQ (OFQ, also known as nociceptin) has been proposed to oppose the antinociceptive effect of endogenous opioid peptides in the brain. We sought to determine whether, conversely, the endogenous opioid peptides counteract a pronociceptive action of OFQ.

• In testing this hypothesis, naloxone, a non-selective opioid receptor antagonist, was used to block the action of endogenous opioid peptides. We then examined whether OFQ would produce hyperalgesia in the absence of such an endogenous opioidergic tone.

• Neither naloxone (1 mg kg⁻¹; s.c.) nor OFQ (up to 30 nmol; i.c.v.) alone induced any significant change in mean hot plate latency. However, OFQ dose-dependently produced hyperalgesia in rats pretreated with naloxone, implying that OFQ can indeed produce hyperalgesia once an endogenous opioidergic tone is inhibited.

• In subsequent studies, we used subtype selective opioid receptor antagonists to determine which class of opioid receptor is involved in this response. The effect of naloxone was reproduced using the selective μ-opioid receptor antagonist CTOP (D-Phe-Cyc-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2), but not by administration of the δ-opioid receptor antagonist, naltrindole (NTI) or the κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI).

• These results suggest that endogenous opioid peptides acting at the μ-, but not κ- or δ-opioid receptor may be counteracting the hyperalgesic effect of OFQ in rats.

British Journal of Pharmacology (2000) 131, 1684–1688; doi:10.1038/sj.bjp.0703746