Sympathetic vasoconstrictor antagonism and vasodilatation relieve mechanical allodynia in rats with chronic postischemia pain.

Abstract

UNLABELLED:

Chronic pain that responds to antisympathetic treatments and alpha-adrenergic antagonists is clinically referred to as sympathetically maintained pain. Animal models of neuropathic pain have shown mixed results in terms of antinociceptive effectiveness of antisympathetic agents. The effectiveness of these agents have not been yet investigated in animal models of complex regional pain syndrome-type 1 (CRPS-I). In this study, we examined the effectiveness of antisympathetic agents and sympathetic vasoconstrictor antagonists, as well as agents that are vasodilators, in relieving mechanical allodynia in a recently developed animal model of CRPS-I (chronic postischemia pain or CPIP) produced by 3 hours of hind paw ischemia-reperfusion injury. Systemic guanethidine, phentolamine, clonidine, and prazosin are effective in reducing mechanical allodynia particularly at 2 days after reperfusion, and less so at 7 days after reperfusion. A nitric oxide donor vasodilator, SIN-1, also reduces mechanical allodynia more effectively at 2 days after reperfusion, but not at 7 days after reperfusion. These results suggest that the pain of CPIP, and possibly also CRPS-I, is relieved by reducing sympathetically mediated vasoconstriction, or enhancing vasodilatation.

PERSPECTIVE:

The results of this study indicate that sympathetic block, or administration of alpha(1)-adrenergic antagonists, clonidine, or a nitric oxide donor, relieve allodynia in an animal model of CRPS-I. Thus, the pain of CRPS-I may depend on enhanced vasoconstrictor responsiveness, which may be relieved by blocking sympathetic efferent-dependent vasoconstriction, or by enhancing nitric oxide-dependent vasodilatation.

• Authors: Dimitris N Xanthos, Terence J Coderre
• Journal: The journal of pain (J Pain) Vol. 9 Issue 5 Pg. 423-33 (May 2008) ISSN: 1526-5900 [Print] United States
• PMID: 18262849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Nitric Oxide Donors
• Vasodilator Agents

Topics

• Adrenergic alpha-Agonists (pharmacology, therapeutic use)
• Adrenergic alpha-Antagonists (pharmacology, therapeutic use)
• Animals
• Chronic Disease
• Complex Regional Pain Syndromes (drug therapy, etiology, physiopathology)
• Disease Models, Animal
• Hyperalgesia (drug therapy, etiology, physiopathology)
• Male
• Microcirculation (drug effects, physiopathology)
• Nitric Oxide Donors (pharmacology, therapeutic use)
• Pain Measurement (drug effects)
• Rats
• Rats, Long-Evans
• Regional Blood Flow (drug effects, physiology)
• Reperfusion Injury (complications, physiopathology)
• Sympathetic Fibers, Postganglionic (drug effects, physiopathology)
• Treatment Outcome
• Vasoconstriction (drug effects, physiology)
• Vasodilator Agents (pharmacology, therapeutic use)