The Effect of alpha2 Adrenoceptors and Imidazoline Receptors on the Mechanical Allodynia in Rats with Nerve Ligation Injury. |
Jai Hyun Hwang, Young Kook Kim, Jong Yeon Park, Hee Jung Jun |
Department of Anesthesiology, College of Medicine, University of Ulsan, Seoul, Korea. |
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Abstract |
BACKGROUND Clonidine, an alpha2 adrenoceptor agonist, has been known to have an antiallodynic effect in many animal and human studies. Clonidine, however, acts on imidazoline receptors as well as alpha2 adrenoceptors. Recently, the effect of clonidine on the symapthetic nervous system was reported to be mediated via the activation of the imidazoline receptor system but not the alpha2 adrenergic receptor system. Therefore, we conducted a behavioral test to investigate the effects of alpha2 adrenoceptors and imidazoline receptors on mechanical allodynia in rats with spinal nerve ligation (SNL) injury. METHODS Male Sprague Dawley rats were prepared with tight ligation of the left lumbar 5th and 6th spinal nerves and chronic lumbar intrathecal catheter implantation for drug administration. Using a von Frey hair (VFH) test, we examined the effects of intrathecal (IT) brimonidine (0.03 - 3 microgram), clonidine (3 - 10 microgram), and rilmenidine (1 - 30 microgram) in SNL rats. Measurements of the baseline value VFH test was conducted at each dose to compare with the preoperative state. In addition, an antagonistic study with rauwolscine or yohimbine was performed to investigate the reversal of antiallodynic effects of each agonist. Allodynic thresholds for the withdrawal response of the left lesioned hindpaw to VFH stimuli were assessed and converted to %MPE. RESULTS The antiallodynic effects of brimonidine, clonidine, and rilmenidine were produced in a dose dependent manner. The antiallodynic effects of IT brimonidine but not rilmenidine were significantly antagonized by alpha2 antgonists rauwolscine and yohimbine (P < 0.05). CONCLUSIONS The results suggest that mechanical allodynia produced by a SNL injury is reduced by an imidazoline receptor agonist as well as alpha2 adrenergic receptor agonists and sympathetic activation is more likely mediated by spinal imidazoline receptors. |
Key Words:
Agonist: brimonidine; clonidine; rilmenidine; Antagonist: rauwolscine; yohimbine; Injection: intrathecal; intraperitoneal; Receptor: alpha2 adrenergic; imidazoline; Pain: allodynia |
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