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  • Title: Nociceptin (orphanin FQ), an endogenous ligand for the QRL1 (opioid-receptor-like1) receptor; modulates responses of trigeminal neurons evoked by excitatory amino acids and somatosensory stimuli.
    Author: Wang XM, Zhang KM, Mokha SS.
    Journal: J Neurophysiol; 1996 Nov; 76(5):3568-72. PubMed ID: 8930296.
    Abstract:
    1. This is the first in vivo electrophysiological evidence demonstrating the effects of Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln (nociceptin or orphanin FQ), an endogenous ligand for the orphan ORL1 receptor, on nociceptive neurons in the CNS. The effects of nociceptin were tested on the responses of neurons recorded in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in the rat. 2. Nociceptin applied microiontophoretically produced a predominantly long-lasting (5-30 min) inhibitory modulation of the N-methyl-D-aspartic acid (NMDA)-evoked responses of 24 of 31 nociceptive and 12 of 12 nonnociceptive neurons. Excitatory or biphasic effects of nociceptin were also observed in 6 of 43 neurons. Responses evoked by (+/-)-alpha-amino-3-hydroxy-5-methylisox-azole-4-propionic acid (AMPA) were reduced in eight of nine nociceptive and nonnociceptive neurons. 3. The inhibitory effect of nociceptin was not modality specific; responses to both noxious and nonnoxious stimuli were reduced. 4. Although naloxone applied iontophoretically blocked or reduced the peak inhibitory effect of [D-Ala2,N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or trans-(+/-)-3,4-dicholoro-N-methyl-N-(2-1-pyrrolidinyl-cyclo hexyl)-benzene acetamide (U50, 488H), it did not produce a significant alteration in the peak inhibitory effect of nociceptin. 5. Nociceptin administered intracerebroventricularly produced a long-lasting (20-35 min) reduction in the NMDA-evoked responses of three of three nociceptive neurons. 6. Nociceptin produces a predominantly antinociceptive action in the trigeminal system.
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