Effects of estrogen and progesterone on acute nociception responses and the development of opioid tolerance.

摘要

A growing body of anatomical, endocrinological and behavioral data suggests that there are significant differences between males and females in their responses to nociceptive stimuli and that steroidal hormones play an important role in modulating the response to such stimuli in females. We tested this possibility by experiments using ovariectomized (OVX) rats and administering estrogen, progesterone or estrogen plus progesterone with acute pain treatments. Estradiol increased and progesterone decreased the latency of responses to acute pain (hot water tail flick test) and the co-administration of estradiol and progesterone had dose-dependent effects. We then examined the latency when using morphine, U50, 488 and SNC80.; Overall, morphine increased the latency. Similarly, U50, 488 also increased the latency. SNC80, a delta opioid agonist affected latency to tail flick in a temperature and dose-dependant manner. To the degree that gonadal hormones influence nociceptive responses, this finding suggest that the K and delta-opioid receptors might be more sensitive to gonadal hormone treatments that the mu-opioid receptors. Estrogen and progesterone did not affect the acquisition of tolerance; levels of morphine-induced anti-nociception were similar between experimental groups. Furthermore, co-administration of both steroids did not alter the formation of tolerance in OVX rats. Administration of progesterone during the acquisition phase had no effect on the development of tolerance. However, when progesterone was administered during the expression phase, the latencies were significantly reduced when compared to rats receiving estrogen alone. Based on the complexity of the responses found in our study, this suggest that the roles of progesterone and estradiol as they vary throughout the estrus/menstrual cycle will not be uncovered until we are able to replicate the cycle rather than model the cycle with constant hormone levels.