Sex differences in opioid-induced immune alterations

Opioids produce sexually dimorphic effects on a variety of behavioral and physiological outcomes, however putative sex differences in the immune altering effects of opioids remain largely unexplored. One previous report documented that morphine and other mu-opioids produced greater enhancement of the cutaneous contact hypersensitivity response in females than males. To extend the findings of this initial study, this investigation tested whether activation of other opioid receptor subtypes also produced sex differences in their effects on contact hypersensitivity. A second major aim was to explore the immunological and neurogenic determinants of morphine-induced sex differences in contact hypersensitivity. Experiments employed pinna swelling and molecular biological assessments of immune status as primary endpoints.; The experiments presented in Chapter 2 revealed that the kappa-opioid spiradoline but not the delta-opioid SNC80 produced greater increases in pinna swelling in females than males when administered prior to elicitation of contact hypersensitivity. This pattern of results contrasted with the effects of kappa- and delta-opioids on nociceptive responses, urine output, and locomotor activity.; Chapter 3 summarizes experiments conducted to determine the immunological underpinnings of sex differences in morphine enhancement of contact hypersensitivity. Realtime reverse transcriptase polymerase chain reaction was conducted on inflamed pinna tissue from 6--72 hours following elicitation of contact hypersensitivity.{09}The observed pattern of results indicated that sex differences in morphine enhancement of contact hypersensitivity are due to preferential recruitment of CD8+ T-lymphocytes to the pinnae of females and subsequent activation of these cells.; The experiments outlined in Chapter 4 tested whether the peripheral neurokinin 1 receptor system is a mediator of morphine-induced sex differences in contact hypersensitivity. Treatment with the neurokinin 1 receptor antagonist SR140,333 selectively antagonized the proinflammatory effects of morphine in females but not males.; These experiments demonstrate the specificity of sex differences in opioid effects on contact hypersensitivity to agonists at mu and kappa receptors. The data also implicate CD8+ T-lymphocytes and peripheral NK1 receptors as key mediators underlying sex differences in opioid modulation of contact hypersensitivity. Overall, the present report highlights the need to consider sex as a determinant of opioid-induced immune alterations.