Partial peripheral neuropathy and denervation induced adrenoceptor supersensitivity. Functional studies in an experimental model.
Sciatic nerve ligation in rats (chronic constriction injury (CCI)) induces clinical signs and symptoms that mimic human conditions of neuropathic origin, such as reflex sympathetic dystrophy (RSD). Denervation-induced supersensitivity to (circulating) catecholamines has been implicated in sympathetic dysfunction in the CCI model as well as in RSD. In the present paper we studied functional properties of sympathetic innervation in subcutaneous resistance arteries, isolated from the hind paw of rats 3 weeks after ligation. Contractile responses to electric field stimulation of adrenergic nerves and exogenously administered cumulative doses of various adrenergic agonists were studied using a myograph. As compared to the contralateral side, subcutaneous arteries from the ligated side were less responsive to electrical field stimulation. Besides, as compared to the contralateral side, subcutaneous arteries from the ligated side showed increased sensitivity to alpha 1-adrenoceptor stimulation. This study demonstrates that sympathetic dysfunction in an experimental model of neuropathic pain consists of denervation-induced supersensitivity to catecholamines rather than of an afferently-induced increase in efferent sympathetic nerve impulses.
Kurvers
H
H
Department of Surgery, University Hospital Maastricht, The Netherlands.
Daemen
M
M
Slaaf
D
D
Stassen
F
F
van den Wildenberg
F
F
Kitslaar
P
P
de Mey
J
J
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D001381:Azepines / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood / Q000502:physiology; D003714:Denervation; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation; D006801:Humans; D008026:Ligation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D012019:Reflex Sympathetic Dystrophy / Q000209:etiology / Q000503:physiopathology*; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002395:Catecholamines; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C015603:azepexole; D009638:Norepinephrine