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


CONCLUSIONS
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.
Nozaki-Taguchi
Natsuko
N
Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
Yaksh
Tony L
TL
D000287:Administration, Topical; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D002056:Burns / Q000150:complications / Q000503:physiopathology*; D006614:Hindlimb; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D007278:Injections, Spinal; D008139:Loperamide / Q000008:administration & dosage; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects*; D009475:Neurons, Afferent / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D000077208:Remifentanil; D013116:Spinal Cord / Q000378:metabolism*; D014110:Touch
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010880:Piperidines; D017450:Receptors, Opioid, mu; D009270:Naloxone; D008139:Loperamide; D009020:Morphine; D000077208:Remifentanil