Chronic post-ischemia pain (CPIP): a novel animal model of complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) produced by prolonged hindpaw ischemia and reperfusion in the rat.
A neuropathic-like pain syndrome was produced in rats following prolonged hindpaw ischemia and reperfusion, creating an animal model of complex regional pain syndrome-Type I (CRPS-I; reflex sympathetic dystrophy) that we call chronic post-ischemia pain (CPIP). The method involves placing a tourniquet (a tight fitting O-ring) on one hindlimb of an anesthetized rat just proximal to the ankle joint for 3 h, and removing it to allow reperfusion prior to termination of the anesthesia. Rats exhibit hyperemia and edema/plasma extravasation of the ischemic hindpaw for a period of 2-4 h after reperfusion. Hyperalgesia to noxious mechanical stimulation (pin prick) and cold (acetone exposure), as well as mechanical allodynia to innocuous mechanical stimulation (von Frey hairs), are evident in the affected hindpaw as early as 8 h after reperfusion, and extend for at least 4 weeks in approximately 70% of the rats. The rats also exhibit spontaneous pain behaviors (hindpaw shaking, licking and favoring), and spread of hyperalgesia/allodynia to the uninjured contralateral hindpaw. Light-microscopic examination of the tibial nerve taken from the region just proximal to the tourniquet reveals no signs of nerve damage. Consistent with the hypothesis that the generation of free radicals may be partly responsible for CRPS-I and CPIP, two free radical scavengers, N-acetyl-L-cysteine (NAC) and 4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl (Tempol), were able to reduce signs of mechanical allodynia in this model.
Coderre
Terence J
TJ
Department of Anesthesia, Anesthesia Research Unit, McGill University, Room 1203, McIntyre Bldg, 3655 Drummond St., Montreal, Que., Canada H3G 1Y6. terrence.coderre@mcgill.ca
Xanthos
Dimitris N
DN
Francis
Laura
L
Bennett
Gary J
GJ
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000473:pathology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D012019:Reflex Sympathetic Dystrophy / Q000188:drug therapy / Q000473:pathology*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology*
D016166:Free Radical Scavengers