Neurokinin 1 receptor signaling mediates sex differences in mu and kappa opioid-induced enhancement of contact hypersensitivity.
Contact hypersensitivity (CHS) is a type of cutaneous inflammation that is exacerbated by neurogenic factors. Both mu- and kappa-opioids enhance CHS to a greater extent in females than males. It was hypothesized that potentiated neurokinin 1 (NK1) receptor signaling following opioid treatment accounts for sex differences in the magnitude of CHS. Following morphine or spiradoline treatment the NK1 receptor antagonist SR140,333 significantly attenuated the magnitude of CHS in females but not males. By contrast, the NK2 antagonist SR48968 had no effect on morphine modulation of CHS. Taken together, these data indicate that NK1 receptor signaling is a key mediator of sex differences in opioid-induced enhancement of CHS.
Elliott
Jay C
JC
Department of Psychology, CB # 3270, Davie Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA. elliojc@musc.edu
Wagner
Alison F
AF
Lysle
Donald T
DT
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D013373:Substance P / Q000378:metabolism
D000701:Analgesics, Opioid; D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011759:Pyrrolidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D009020:Morphine; C051272:spiradoline