Morphine-induced analgesia, hypotension, and bradycardia are enhanced in hypertensive rats

Several studies have emphasized an opioidergic link between the central regulation of cardiovascular function and acute noninflammatory pain. By contrast, relatively few studies have investigated the relationships between opioids, hypertension, and inflammatory pain. We used the formalin model of acute inflammatory pain to compare morphine antinociception among spontaneously hypertensive (SHR) rats, their genetic normotensive controls, Wistar-Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. Measures of nociception included both behavioral and cardiovascular end-points (increased mean arterial blood pressure and heart rate). Morphine (3.0 mg/kg subcutaneously) produced greater hypotension and bradycardia in SHR than in WKY or SD rats. We next administered formalin (5%;50 μL) and observed greater nociception during both Phase 1 and Phase 2 in SHR controls than in WKY controls. The morphine-treated groups did not differ, suggesting that morphine attenuates hypersensitivity to formalin pain in the SHR. Morphine inhibited edema but not paw hyperthermia to a greater degree in SHR, whereas Phase 1 remifentanil produced a relatively shorter delay in the onset of Phase 2 in SHR. We suggest that the presentation of essential hypertension be considered when opioid regimens are planned both during surgery (to minimize cardiovascular complications) and during the postoperative period (to optimize analgesic effects).