Oxytocin-induced analgesia and scratching are mediated by the vasopressin-1A receptor in the mouse.
The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) contribute to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Here, we characterized the phenotype of oxytocin receptor (OTR) and vasopressin-1A receptor (V1AR) null mutant mice in a battery of pain assays. Surprisingly, OTR knock-out mice displayed a pain phenotype identical to their wild-type littermates. Moreover, systemic administration of OXT dose-dependently produced analgesia in both wild-type and OTR knock-out mice in three different assays, the radiant-heat paw withdrawal test, the von Frey test of mechanical sensitivity, and the formalin test of inflammatory nociception. In contrast, OXT-induced analgesia was completely absent in V1AR knock-out mice. In wild-type mice, OXT-induced analgesia could be fully prevented by pretreatment with a V1AR but not an OTR antagonist. Receptor binding studies demonstrated that the distribution of OXT and AVP binding sites in mouse lumbar spinal cord resembles the pattern observed in rat. AVP binding sites diffusely label the lumbar spinal cord, whereas OXT binding sites cluster in the substantia gelatinosa of the dorsal horn. In contrast, quantitative real-time reverse transcription (RT)-PCR revealed that V1AR but not OTR mRNA is abundantly expressed in mouse dorsal root ganglia, where it localizes to small- and medium-diameter cells as shown by single-cell RT-PCR. Hence, V1ARs expressed in dorsal root ganglia might represent a previously unrecognized target for the analgesic action of OXT and AVP.
Schorscher-Petcu
Ara
A
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 1B1, Canada.
Sotocinal
Susana
S
Ciura
Sorana
S
Dupré
Anouk
A
Ritchie
Jennifer
J
Sorge
Robert E
RE
Crawley
Jacqueline N
JN
Hu
Shuang-Bao
SB
Nishimori
Katsuhiko
K
Young
Larry J
LJ
Tribollet
Eliane
E
Quirion
Rémi
R
Mogil
Jeffrey S
JS
D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000008:administration & dosage; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D007175:Impulsive Behavior / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009951:Ornipressin / Q000031:analogs & derivatives / Q000494:pharmacology; D010121:Oxytocin / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000009:adverse effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000172:deficiency; D017483:Receptors, Vasopressin / Q000172:deficiency / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects
D000700:Analgesics; D065092:Antidiuretic Hormone Receptor Antagonists; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C074541:vasotocin, desGly(NH2)(9)d(CH2)5-Tyr(Me)(2)-Thr(4)-Orn(8)-; D009951:Ornipressin; D010121:Oxytocin