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PAIN MEDICINE

Spinal and Peripheral µ Opioids and the Development of Secondary Tactile Allodynia After Thermal Injury

Department of Anesthesiology, University of California, San Diego

Address correspondence and reprint requests to T. L. Yaksh, PhD, Department of Anesthesiology, University of California–San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0818. Address e-mail to tyaksh{at}ucsd.edu

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°TA). We sought to define the peripheral and spinal actions of µ opioids in regulating 2°TA. First, a mild thermal injury was induced on one heel, producing 2°TA. This 2°TA was blocked by pretreatment, but not posttreatment, with a topical µ-opioid agonist, loperamide (1.7%–5%). Second, 2°TA was blocked by intrathecal morphine (0.1–10 µg) pre- and postinjury. 2°TA reappeared when systemic naloxone was given before, but not after, injury in intrathecal morphine-pretreated rats. Intrathecal remifentanil, a short-lasting µ-opioid agonist, infused periinjury (3 µg/min), did not block subsequent primary thermal hyperalgesia, but it produced a dose-dependent (0.3–3 µg/min) abolition of 2°TA. Local tissue injury leads to 2°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.

IMPLICATIONS: 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.

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