Hyperemia of injured peripheral nerve: sensitivity to CGRP antagonism.
Intrinsic mechanisms of vasodilatation may prevent injury-related ischemia in peripheral nerve endoneurium. We examined local perfusion up to 10 days following local crush, partial injury or simple exposure of the rat sciatic nerve. By employing epineurial hCGRP(8-37), a receptor antagonist of CGRP, and serial hydrogen clearance measurements, we estimated the component of post-injury blood flow related to local CGRP action. Injury-related ischemia was not observed at any of the time points studied at or proximal to injury. Instead, endoneurial blood flow (EBF) increased at 24 h proximal to crush or partial injury, and at 48 h within the crush zone when compared to sham operated controls or to a pooled reference range of EBF. Composite blood flow (F) was also elevated at 48 h and 5 days within the crush zone suggesting hyperemia involving the epineurial plexus, perineurial vessels and AV shunts. hCGRP(8-37) constricted vasa nervorum at most time points but its effect on EBF was maximum and exceeded controls within the crush zone at 48 h. The findings indicate that certain types of nerve injury, including focal crush, are associated with hyperemia, not ischemia. CGRP vasodilatation may account for part of this response, implying a local peptidergic afferent fiber response to nerve trunk injury.
Zochodne
D W
DW
Peripheral Nerve Research Laboratory, Queen's University, Kingston, Ont., Canada.
Ho
L T
LT
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D006940:Hyperemia / Q000209:etiology*; D008297:Male; D008657:Metabolic Clearance Rate; D008833:Microcirculation / Q000187:drug effects; D008839:Microelectrodes; D009409:Nerve Crush; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D012584:Sciatic Nerve / Q000293:injuries*; D012680:Sensitivity and Specificity; D014655:Vascular Resistance / Q000187:drug effects
D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide