Sciatic cryoneurolysis in rats: a model of sympathetically independent pain. Part 2: Adrenergic pharmacology.
The purpose of this study was to investigate the possibility that sympathetic exacerbation of neuropathic pain activity may be mediated in part by the development of abnormal peripheral adrenergic mechanisms at the site of peripheral nerve injury. We evaluated changes in mechanical stimulation withdrawal thresholds before and after the delivery of selected alpha-adrenergic agonists and antagonists to the immediate area of a prior nerve injury in rats that had developed continuous mechanical allodynia subsequent to sciatic cryoneurolysis (SCN). Allodynia was attenuated (thresholds increased) after administration of the alpha 1 antagonist prazosin, but not the alpha 2 antagonist idazoxan. Similar attenuation occurred with infusions of the alpha 2 agonist dexmedetomidine and at the lowest dose (2.0 micrograms) of the mixed alpha agonist clonidine. In contrast, allodynia was exacerbated (thresholds decreased) by infusion of the highest dose of clonidine (20 micrograms). Infusions of the alpha 2 agonist ST-91, a polar analog of clonidine, did not alter withdrawal thresholds. The findings suggest that a minimal peripheral adrenergic modulation of SCN-induced allodynia occurs via mechanisms that are not localized to the prior injury site. However, overall, the SCN model of neuropathic pain appears to be resistant to adrenergic interventions, providing further evidence that SCN in rats is a model of sympathetically independent pain (SIP).
Willenbring
S
S
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, USA.
DeLeo
J A
JA
Coombs
D W
DW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003452:Cryosurgery; D003714:Denervation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology / Q000601:surgery*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists