Regulation of galanin gene expression in human keratinocytes

Morphine produces an exacerbation of DNFB-induced cutaneous inflammation when administered prior to antigen challenge in a rat model of contact hypersensitivity (CHS). Recent evidence indicates that this exacerbation of inflammation is significantly greater in females than that in males. This sex difference in morphine modulation of CHS is due to the activation of central μ-opioid receptor pathways and appears to be corticosterone independent. Furthermore, the presence of female gonadal hormones may account for observed the sex differences, because ovariectomy largely eliminates morphine's enhancement of CHS inflammation without affecting the basal CHS response. Given the involvement of substance P in the pathological exacerbation of CHS, we hypothesized that sex differences in NK1 receptor activation might account for morphine's greater effect on the expression of CHS in females. To that end, male and female CDF rats were treated with the selective NK1 receptor antagonist SR140 333 (1 mg/kg, subcutaneously) 150 min prior to and after DNFB challenge. SR140 333 treatment significantly reduced the magnitude of morphine's enhancement of CHS in female, but not male rats without affecting the baseline CHS response in either sex. Preliminary data suggest that neuropeptide depletion of the skin using capsaicin produces a similar pattern of sex-dependent effects on morphine modulation of CHS. Taken together, these experiments support the hypothesis that greater activity of the peripheral NK1 receptor system in females may in part account for sex differences in the magnitude of CHS following morphine treatment.
This project was supported by NIH grants DA15709 (D.T.L.) and DA016836 (J.C.E). SR140 333 was generously provided by Sanofi-Synthelabo.