Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in regulating pain and itch in non-human primates.
OBJECTIVE
Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non-human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans.


METHODS
Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail-withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses.


RESULTS
Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal μ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses.


CONCLUSIONS
Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ-NOP receptor system in pain processing but also supports the therapeutic potential of NOP-related ligands as analgesics.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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H
Ding
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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K
Hayashida
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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T
Suto
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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DD
Sukhtankar
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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M
Kimura
Preclinical Translational Services, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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V
Mendenhall
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.|Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.|Center for Comparative Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
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http://orcid.org/0000-0003-2436-4506
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Ko
D000818:Animals; D001522:Behavior, Animal; D002404:Catheterization; D002946:Cisterna Magna; D005260:Female; D007278:Injections, Spinal; D008161:Lumbosacral Region; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D011537:Pruritus / Q000378:metabolism*; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009020:Morphine; D018847:Opioid Peptides; D011957:Receptors, Opioid; D013373:Substance P; D000094942:Nociceptin Receptor; D000097629:Nociceptin