Neurokinin 1 receptor signaling mediates sex differences in μ and κ opioid-induced enhancement of contact hypersensitivity

Contact hypersensitivity (CHS) is a type of cutaneous inflammation that is exacerbated by neurogenic factors. Both μ- and κ-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.