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

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.
AuthorsH Wei, E Jyväsjärvi, S Niissalo, M Hukkanen, E Waris, Y T Konttinen, A Pertovaara
JournalNeuroscience (Neuroscience) Vol. 114 Issue 3 Pg. 655-68 ( 2002) ISSN: 0306-4522 [Print] United States
PMID12220567 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2002 IBRO
Chemical References
  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Analgesics
  • Imidazoles
  • Indans
  • Receptors, Adrenergic, alpha-2
  • radolmidine
  • 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)

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