Abstract |
Spinal norepinephrine release and activation of spinal alpha(2)-adrenergic receptors represent important components of descending control of nociception. Recent studies have shown that nitric oxide is capable of stimulating neuronal norepinephrine release in the presence of thiol-containing compounds such as L-cysteine. In the present study, we tested a hypothesis in a rodent model of neuropathic pain that intrathecal injection of the nitric oxide donor S-nitroso-N-acetylpenicillamine and L-cysteine produces an antiallodynic action mediated by the spinal alpha(2)-adrenergic receptors. Allodynia was induced in rats by ligation of the left lumbar L5/L6 spinal nerves. Mechanical allodynia was quantified by application of von Frey filaments to the left hindpaw. Intrathecal injection of 20-100microg of S-nitroso-N-acetylpenicillamine in the presence of 200microg of L-cysteine, but not D- cysteine, dose-dependently attenuated the allodynia. Intrathecal injection of a combination of 100microg of S-nitroso-N-acetylpenicillamine and 50-200microg of L-cysteine also inhibited the allodynia in a dose-dependent manner. Pretreatment with a nitric oxide scavenger, carboxy-PTIO, or depletion of norepinephrine with a specific neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, prevented the antiallodynic action of intrathecal S-nitroso-N-acetylpenicillamine and L-cysteine. Furthermore, the antiallodynic effect produced by intrathecal injection of a combination of S-nitroso-N-acetylpenicillamine and L-cysteine was abolished by pretreatment with intrathecal injection of a non-specific alpha-adrenergic receptor antagonist, phentolamine, or an alpha(2) receptor antagonist, idazoxan. This study provides the first functional evidence that spinal nitric oxide interacts with the thiol-containing compounds to produce an antiallodynic effect in neuropathic pain. We propose that such an action is mediated by endogenous norepinephrine and spinal alpha(2)-adrenergic receptors.
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Authors | S R Chen, J C Eisenach, H L Pan |
Journal | Neuroscience
(Neuroscience)
Vol. 101
Issue 3
Pg. 759-65
( 2000)
ISSN: 0306-4522 [Print] United States |
PMID | 11113324
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Nitric Oxide Donors
- Nitroso Compounds
- Receptors, Adrenergic, alpha-2
- S-Nitrosothiols
- S-nitro-N-acetylpenicillamine
- Nitric Oxide
- Mercaptoethanol
- S-nitrosomercaptoethanol
- Penicillamine
- Cysteine
- Norepinephrine
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Topics |
- Animals
- Cysteine
(pharmacology)
- Hyperalgesia
(drug therapy, metabolism, physiopathology)
- Injections, Spinal
(statistics & numerical data)
- Male
- Mechanoreceptors
(drug effects, metabolism, physiopathology)
- Mercaptoethanol
- Nitric Oxide
(metabolism)
- Nitric Oxide Donors
(pharmacology)
- Nitroso Compounds
(metabolism)
- Norepinephrine
(metabolism)
- Pain Threshold
(drug effects, physiology)
- Penicillamine
(analogs & derivatives, pharmacology)
- Peripheral Nerve Injuries
- Peripheral Nerves
(pathology, physiopathology)
- Peripheral Nervous System Diseases
(drug therapy, metabolism, physiopathology)
- Physical Stimulation
(adverse effects)
- Rats
- Rats, Sprague-Dawley
- Receptors, Adrenergic, alpha-2
(drug effects, metabolism)
- S-Nitrosothiols
- Spinal Cord
(drug effects, metabolism, physiopathology)
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