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Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats.

Abstract
This study was conducted to examine the role of nitric oxide (NO) in peripheral neuropathy induced by chronic constriction injury of sciatic nerve of rats by using NO precursor, NO donors and nitric oxide synthase (NOS) inhibitors. Chronic constriction injury of sciatic nerve of rats resulted in peripheral neuropathy as confirmed by nociceptive behavioural tests using mechanical, thermal and cold allodynia. NO precursor, L-arginine and NO donors sodium nitroprusside, S-nitroso-N-acetylpenicillamine potentiated the hyperalgesia and allodynia significantly suggesting proalgesic effect in neuropathic rats. Intracerebroventricular (i.c.v.) administration of rats with NOS inhibitors such as L-N(G)-nitroarginine methyl ester, N-iminoethyl lysine and 7-nitroindazole did not show any effect but i.p. administration of NOS inhibitors aminoguanidine, L-N(G)-nitroarginine methyl ester and 7-nitroindazole caused alleviation of pain. The study confirms the involvement of endogenously synthesized and exogenously administered NO in chronic constriction injury-induced neuropathy in rats. Significant increase in the levels of nitrate and nitrite in ligated sciatic nerve suggest that local up regulation of NO in the production and maintenance of neuropathic pain. In conclusion, initial attempt to manipulate L-arginine: NO pathway is indicative of therapeutic potential of these interventions in the management of neuropathic pain.
AuthorsAjit K Naik, Surendra K Tandan, Dinesh Kumar, Shailesh P Dudhgaonkar
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 530 Issue 1-2 Pg. 59-69 (Jan 13 2006) ISSN: 0014-2999 [Print] Netherlands
PMID16364289 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Nitrates
  • Nitric Oxide Donors
  • Nitrites
  • Nitroprusside
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Arginine
  • Nitric Oxide Synthase
Topics
  • Animals
  • Arginine (pharmacology)
  • Behavior, Animal (drug effects)
  • Cold Temperature (adverse effects)
  • Constriction, Pathologic (complications)
  • Disease Models, Animal
  • Hindlimb (innervation)
  • Hot Temperature (adverse effects)
  • Hyperalgesia (etiology, physiopathology)
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Male
  • Neuralgia (etiology, physiopathology)
  • Nitrates (blood)
  • Nitric Oxide (metabolism, physiology)
  • Nitric Oxide Donors (administration & dosage)
  • Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
  • Nitrites (blood)
  • Nitroprusside (administration & dosage)
  • Pain Threshold (drug effects)
  • Rats
  • Rats, Wistar
  • S-Nitroso-N-Acetylpenicillamine (administration & dosage)
  • Sciatic Nerve (injuries, physiopathology)
  • Stress, Mechanical

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