Abstract
Nociceptin/orphanin FQ (N/OFQ) is involved in many behavioural patterns; in particular, it exerts a modulating effect on nociception. Like other proposed antiopiates, nociceptin/orphanin FQ has been shown to have analgesic, hyperalgesic as well as antianalgesic properties. Among the various effects proposed on nociceptive sensitivity at supraspinal level, the antagonistic activity toward morphine analgesia seems to be of interest. Therefore, we decided to investigate whether nociceptin/orphanin FQ and [Arg 14, Lys 15] nociceptin/orphanin FQ (R-K, a nociceptin analogue) can have the same effect on the analgesia produced by nonopioid analgesics. In this study, we examined the antianalgesic effect of nociceptin/orphanin FQ and its analogue R-K on paracetamol-induced analgesia and evaluated by means of the hot plate test in rats. Nociceptin/orphanin FQ was intracerebroventricularly administered, and, after 5 min, a dose of 400 mg/kg paracetamol was injected intraperitoneally, 30 min before the hot plate test. Nociceptin/orphanin FQ and R-K showed a dose-dependent antagonism on the antinociceptive effect of paracetamol, and the activity of both drugs was significantly reduced by the antagonist [Nphe 1] Arg 14, Lys 15–N/OFQ–NH 2 (UFP-101). These data indicate that nociceptin/orphanin FQ and R-K have an antianalgesic effect on the analgesia produced by a nonopioid analgesic drug, like paracetamol, that seems to develop within the brain.
Highlights
Nociceptin/orphanin has been identified as a potent endogenous agonist of ORL1 receptors currently named as NOP receptor (Cox et al, 2000)
The highest dose used of nociceptin/orphanin FQ completely abolished the effect of paracetamol
We have demonstrated that nociceptin/orphanin FQ and its analogue R-K are able to antagonize in a dose-dependent manner the antinociceptive effect of paracetamol in the hot plate test
Summary
Nociceptin/orphanin has been identified as a potent endogenous agonist of ORL1 receptors currently named as NOP receptor (Cox et al, 2000). This 17-amino acid peptide shares a structure related to the peptide dynorphin A 1–17 (Julius, 1995). NOP receptor signalling is involved in several spinal and supraspinal actions, including opiate tolerance, dependence/withdrawal, adaptive response to anxiety and stress, reward, memory and pain (for a review, see Meis, 2003). The action on pain modulation seems to differ at spinal and supraspinal levels, creating in turn hyperalgesia, analgesia or antianalgesia, evidence of the reported phenomena is not robust (Mogil and Pasternak, 2001). A functional antiopioid activity of nociceptin/orphanin FQ has been described (Mogil et al, 1996); when intracerebroventricularly (i.c.v.) injected, nociceptin/orphanin FQ can
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