Introduction

When given systemically, the prototypical opioid analgesic morphine attenuates pain arising from the viscera. Indeed, malignancies and obstructions of the viscera caused by tumors are routinely treated with opioids such as morphine. Although it has long been held that opioids produce analgesia principally by actions in the central nervous system, it is now widely appreciated that opioids also have direct effects in the periphery, particularly in the presence of tissue injury (as detailed in Chapter 5 of this volume). Because of an interest in mechanisms of visceral pain, we undertook development of an appropriate model (colorectal distension in the rat) and then carried out studies to examine the efficacy and potency of opioids in the modulation of responses to colonic distension. That colorectal distension is both an appropriate and useful model for the study of visceral pain in humans and nonhuman animals has been documented (Ness and Gebhart, 1988; Ness et al., 1990; Gebhart and Sengupta, 1995). Balloon distension of the gut produces sensations similar in intensity, quality, and localization to those experienced in functional bowel disorders. In unanesthetized rats, responses to colorectal distension include supraspinally organized visceromotor and pressor responses. Both the visceromotor and pressor responses to distension are attenuated by morphine, whether given systemically or directly into the intrathecal space where afferent fibers innervating the colon terminate (Ness and Gebhart, 1988; Danzebrink et al., 1995; Harada et al., 1995).