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

Abstract

Local thermal injury to the paw 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; 2 degrees TA). We sought to define the peripheral and spinal actions of mu opioids in regulating 2 degrees TA. First, a mild thermal injury was induced on one heel, producing 2 degrees TA. This 2 degrees TA was blocked by pretreatment, but not posttreatment, with a topical mu-opioid agonist, loperamide (1.7%-5%). Second, 2 degrees TA was blocked by intrathecal morphine (0.1-10 microg) pre- and postinjury. 2 degrees TA 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 microg/min), did not block subsequent primary thermal hyperalgesia, but it produced a dose-dependent (0.3-3 microg/min) abolition of 2 degrees TA. Local tissue injury leads to 2 degrees TA by the activation of opiate-sensitive afferents and the initiation of a cascade that persists in the absence of that initiating injury-induced stimulus. Sensitivity to touch observed in areas adjacent to injury is blocked by opioids applied before, but not after, injury. This suggests that injury-activated opioid-sensitive fibers are responsible for sensitization and reveals a cascade that is diminished by pretreatment but not posttreatment, providing a rationale for adequate analgesia before injury (surgery) has occurred.