Antinociceptive effects of spinally administered nociceptin/orphanin FQ and its N-terminal fragments on capsaicin-induced nociception

  title={Antinociceptive effects of spinally administered nociceptin/orphanin FQ and its N-terminal fragments on capsaicin-induced nociception},
  author={Soh Katsuyama and Hirokazu Mizoguchi and Takaaki Komatsu and Chikai Sakurada and Minoru Tsuzuki and Shinobu Sakurada and Tsukasa Sakurada},
Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand for the N/OFQ peptide (NOP) receptors, has been shown to be metabolized into some fragments. We examined to determine whether intrathecal (i.t.) N/OFQ (1-13), (1-11) and (1-7) have antinociceptive activity in the pain-related behavior after intraplantar injection of capsaicin. The i.t. administration of N/OFQ (0.3-1.2 nmol) produced an appreciable and dose-dependent inhibition of capsaicin-induced paw-licking/biting response. The N-terminal… 
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A series of (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] analogs was designed, synthesized, and biologically evaluated in vitro to seek and identify potent and selective, small-molecules of nonpeptide NOP receptor antagonists, which resulted in the discovery of novel potent small- molecule 15 with high human Nop receptor selectivity over human μ receptor.
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The nociceptin/orphanin FQ receptor system as a target to alleviate cancer‐induced bone pain in rats: Model validation and pharmacological evaluation
The analgesic potential of NOP receptor activation in a rodent cancer‐induced bone pain model is investigated and broad analgesic properties in Nociceptin/orphanin FQ peptide (NOP) receptor agonists are demonstrated.
Expression patterns of nociceptin in rats following experimental tooth movement.
The expression levels of nociceptin were elevated following experimental tooth movement due to bilateral innervation of anterior teeth and bilateral projection of nerve fibers, and the expression levels were similar between ipsilateral and contralateral sides.
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Effects of intraplantar injections of nociceptin and its N-terminal fragments on nociceptive and desensitized responses induced by capsaicin in mice
The present results indicate that not only nociceptin but also the N-terminal fragment (1-13) possesses a local peripheral antinociceptive action, which may be mediated by peripheral ORL1 receptors.
The putative OP4 antagonist, [Nphe1]nociceptin(1-13)NH2, prevents the effects of nociceptin in neuropathic rats
Results further support, for the first time in a chronic model of pain, the specific antagonistic profile of [Nphe(1]N/OFQ(1-13)NH(2)vs the OP(4) receptor, and this pseudopeptide is an interesting pharmacological tool to better clarify the role of N/OF Q in pathophysiology.
Antinociceptive effects of nociceptin/orphanin FQ administered intrathecally in monkeys.
  • M. Ko, N. Naughton
  • Medicine
    The journal of pain : official journal of the American Pain Society
  • 2009
This study is the first to provide a unique functional profile of intrathecal N/OFQ over a wide dose range in primates, indicating that N/ OFQ or NOP receptor agonists represent a promising target as spinal analgesics for clinical trials.
Spinal analgesic activity of orphanin FQ/nociceptin and its fragments
Antisense probes targeting the second and third coding exons, but not the first exon, of the cloned mouse OFQ/nociceptin receptor (KOR-3) partially block OfQ/N analgesia.
Involvement of tachykinin NK1 receptors in nociceptin-induced hyperalgesia in mice
The results obtained suggest that the hyperalgesic effect of nociceptin may be mediated through tachykinin NK1 receptors in the spinal cord.
Pharmacological characterization of orphanin FQ/nociceptin and its fragments.
The results suggest that OFQ/N elicits both analgesia and hyperalgesia through pharmacologically distinct receptors that do not correspond to traditional opioid receptors.
Metabolic fate of nociceptin/orphanin FQ in the rat spinal cord and biological activity of its released fragment
Biologic activity of shorter nociceptin fragments still possess their biologic activity though possibly acting via receptors other than ORL1, as indicated by results of metabolism of orphanin FQ/nocice leptin in rats.
Evidence that N-terminal fragments of nociceptin modulate nociceptin-induced scratching, biting and licking in mice
The results suggest that N-terminal fragments formed endogenously in the spinal cord may have an antagonistic effect on nociceptin-induced behavioral responses.
Orphanin FQ acts as a supraspinal, but not a spinal, anti‐opioid peptide
The findings indicate that the anti-opioid actions of OFQ are restricted to supraspinal central nervous system sites, and not to systemic morphine antinociception induced by i.c.t. morphine.
Intrathecal [Nphe1]nociceptin( 1-13)NH2 selectively reduces the spinal inhibitory effect of nociceptin.
It is concluded that [Nphe1]nocicept(1-13)NH2 is a selective antagonist of the spinal receptor mediating the inhibitory action of nociceptin and it can be further suggested that the spinal inhibitory effect of nOCiceptin may be tonically active.