Spinal and peripheral μ opioids and the development of secondary tactile allodynia after thermal injury

Local thermal injury to the pay leads to an increased sensitivity to a noxious stimulus applied to the site (primary thermal hyperalgesia) and an increased sensitivity to tactile stimuli in skin sites adjacent to the primary injury (secondary tactile allodynia; 2degreesTA). We sought to define the peripheral and spinal actions of mu opioids in regulating 2degreesTA. First, a mild thermal injury was induced on one heel, producing 2degreesTA. This 2degreesTA was blocked by pretreatment, but not posttreatment, with a topical mu-opioid agonist, loperamide (1.7-5%). Second, 2degreesTA was blocked by intrathecal morphine (0.1-10 mug) pre- and postinjury. 2degreesTA reappeared when systemic naloxone was given before, but not after, injury in intrathecal morphine-pretreated rats. Intrathecal remifentanil, a short-lasting mu-opioid agonist, infused periinjury (3 mug/min), did not block subsequent primary thermal hyporalgesia, but it produced a dose-dependent (0.3-3 mug/min) abolition of 2degreesTA. Local tissue injury leads to 2degreesTA by die activation of opiate-sensitive afferents and the initiation of a cascade that persists in the absence of that initiating injury-induced stimulus.