The influence of chemical sympathectomy on pain responsivity and alpha 2-adrenergic antinociception in neuropathic animals.

Abstract

We studied the effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on pain behavior and alpha(2)-adrenergic antinociception in rats with a spinal nerve ligation-induced neuropathy. For assessment of alpha(2)-adrenergic antinociception, the rats were treated systemically with two alpha(2)-adrenoceptor agonists, one of which only poorly (MPV-2426) and the other very well (dexmedetomidine) penetrates the blood-brain barrier. Moreover, the effect of MPV-2426 on spontaneous activity of dorsal root nerve fibers proximal to the nerve injury was determined. Systemic treatment with 6-OHDA produced a marked decrease in immunocytochemical labeling of sympathetic nerve fibers in the skin but it produced no marked change in basal pain sensitivity to mechanical stimulation either in neuropathic or sham-operated animals. Systemic administration of MPV-2426 and dexmedetomidine produced a dose-dependent tactile antiallodynic effect in neuropathic animals. Intraplantar injection of MPV-2426 had an identical antiallodynic effect independent of whether it was injected into the neuropathic or contralateral hindpaw. In a test of mechanical nociception and hyperalgesia, dexmedetomidine markedly attenuated pain responses in all experimental groups, whereas MPV-2426 had a weak but significant pain attenuating effect only in neuropathic animals. In the tail flick test, both alpha(2)-adrenoceptor agonists had a significant antinociceptive effect. The pain attenuating effect of MPV-2426 was enhanced by pretreatment with 6-OHDA, except in a test of tactile allodynia. MPV-2426-induced modulation of spontaneous activity was not a general property of dorsal root fibers proximal to the injury. The results indicate that a chemical destruction of sympathetic postganglionic nerve fibers innervating the skin does not markedly influence cutaneous pain sensitivity nor is it critical for the alpha(2)-adrenoceptor agonist-induced attenuation of pain behavior in neuropathic or non-neuropathic animals. Chemical sympathectomy, independent of neuropathy, enhanced the pain attenuating effect by MPV-2426, probably due to a peripheral action, whereas in non-sympathectomized control and neuropathic animals peripheral mechanisms have only a minor, if any, role in the alpha(2)-adrenoceptor agonist-induced antinociception.

• Authors: H Wei, E Jyväsjärvi, S Niissalo, M Hukkanen, E Waris, Y T Konttinen, A Pertovaara
• Journal: Neuroscience (Neuroscience) Vol. 114 Issue 3 Pg. 655-68 ( 2002) ISSN: 0306-4522 [Print] United States
• PMID: 12220567 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 IBRO

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-Agonists
• Analgesics
• Imidazoles
• Indans
• Receptors, Adrenergic, alpha-2
• radolmidine

Topics

• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-Agonists (pharmacology)
• Analgesics (pharmacology)
• Animals
• Exploratory Behavior (drug effects, physiology)
• Imidazoles (pharmacology)
• Indans (pharmacology)
• Ligation
• Male
• Pain Measurement (drug effects, methods, statistics & numerical data)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, alpha-2 (physiology)
• Spinal Nerves (injuries)
• Sympathectomy, Chemical (methods, statistics & numerical data)
• Sympathetic Fibers, Postganglionic (drug effects, physiology)