The present study is designed to investigate gender differences in pain and analgesia in the elderly and characterize the role of morphine glucuronides and gonadal steroids in responses to pain and opioids in the elderly. Research efforts will focus on three specific aims.
Aim 1 : Characterize dynamic changes in pain threshold, pain tolerance, pain intensity, and pain relief in elderly women and men. Male and female human subjects will be evaluated for their responses to experimental pain and to morphine.
Aim 2 : Characterize effects of gender on pharmacokinetics of morphine, and its two active metabolites, morphine-3-glucuronide (M3G), in the elderly. The pharmacokinetic parameters will be used to establish specific ratios between morphine and each of the glucuronides. These ratios will be analyzed in respect to gender-specific responses to pain and to hormonal status.
Aim 3 : Attempt to correlate gender-related variability in pain threshold, pain tolerance, pain intensity, and pain relief (characterized in Aim 1) with specific ratios of morphine, M3G, and M6G (estimated in Aim 2). An association between gender, gonadal steroids, and the extent of M3G and M6G involvement in responses to pain and analgesia will be analyzed. The completion of these investigations will develop new knowledge on gender differences in responses to pain and analgesia in the elderly. Furthermore, the results will provide data on contributions of factors such as active morphine metabolites and gonadal steroids to gender- specific responses to pain the elderly. Findings from this study will make an important contribution to our understanding of pain problems in the old, and will positively impact age-related research as well as clinical pain management.
