The Effect of alpha2 Adrenoceptors and Imidazoline Receptors on the Mechanical Allodynia in Rats with Nerve Ligation Injury / 대한마취과학회지

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.

The Effect of Brimonidine Premedication on the Sympathetic Nervous System during Ketamine Anesthesia in the Ratv / 대한마취과학회지

BACKGROUND: The use of ketamine as the sole anesthetic induces marked central sympathetic stimulation, causing an increase of heart rate and blood pressure. alpha2-receptor agonist has been demonstrated to attenuate many of these undesirable effects when used as a premedicant. Brimonidine is a new and highly selective alpha2-receptor agonist, and rauwolscine is a selective alpha2-receptor antagonist with little affinity for imidazoline receptors. Using power spectral analysis of heart rate variability, this study examines the effect of brimonidine premedication during ketamine anesthesia on the changes in the autonomic nervous system. METHODS: From 57 Sprague-Dawley rats, 12 rats were anesthetized by urethane (U Group, 1.5 g/kg), 18 rats by ketamine (K Group, 100 mg/kg, 2 mg/kg/min continuous infusion) intraperitoneal injection after saline premedication. Brimonidine (BK Group, 30 microgram/kg, n=15), brimonidine with rauwolscine (BRK Group, 30 microgram/kg, 20 mg/kg, n=12) were adminstered as a premedicant before induction of ketamine anesthesia. ECG signals were recorded for 5 min after a period of 10 min of anesthetic stabilization. Power spectal analysis of the data was computed, using short-time Fourier transform. The spectral peaks within each measurement were calculated; a low frequency area (0.04~1.0 Hz), a high frequency area (1.0~5.0 Hz), and a total frequency area (0.04~5.0 Hz) were measured. RESULTS: The results documented that the K Group showed sympathetic activation as compared with the U Group (p<0.001). The BK Group showed sympathetic depression compared with the K and BRK Groups (p<0.001). There were no significant differences in sympatho-vagal balance between the K and BRK Groups. CONCLUSIONS: These results suggest that premedication with brimonidine is effective in attenuating the sympathetic stimulatory effect of ketamine.

Relationship between Central alpha2-Adrenoceptors and Pressor Response to Raised Intracranial Pressure in Rabbits

The effects of intraventricular alpha2-adrenoceptor agonist and antagonist, clonidine and rauwolscine, on changes of blood pressure induced by the rise of intracranial pressure were investigated in urethane-anesthetized rabbits. 2) The rise of ICP, induced by the infusion of saline into a balloon placed in the epidural space, was comparatively slow in the beginning of the infusion but became sharp as the infusion proceeded. Corresponding with the gradual increase of ICP, there was a slight decrease in BP. An abrupt rise of BP was observed when ICP showed a sharp increase. 3) Intraventricular rauwolscine 5(microgram) by itself did not affect BP. In these rauwolscine-treated rabbits the increase of both ICP and BP by the infusion was similar to that of the control animals. 4) The pretreatment with rauwolscine 50(microgram) did hardly affect BP, but this made the increase of ICP and BP by the infusion different from that of the control animals. The slight hypotensive response in the beginning of the infusion did not appear and the pressor response to the raised ICP was markedly facilitated. The volume of saline inused into the infusing balloon to cause the same increase of ICP as in the control animals was much smaller than in the control ones, and the magnitude of the maximal increase of BP was much greater. 5) The pretreatment with 500 microgram of intraventricular rauwolscine produced an increase of BP. In these animals the increase of both ICP and BP by the infusion seemed to be slightly facilitated than in the control animals. 6) Intraventricular clonidine 30(microgram) markedly decreased BP. In these clonidine-treated animals the slight hypotensive response in the beginning was more distinct than in the control animals, and the pressor response was hardly seen. 7) The hypotensive response to intraventricular clonidine 30(microgram) was weakened in the animals pretreated with intraventricular rauwolscine 500(microgram). In these animals the increase of both ICP and BP by the infusion appeared as in the control animals. 8) The above results suggest that the pressor response to the raised ICP in rabbits was inhibited under the condition of stimulation of central alpha2-adrenoceptors and facilitated under the condition of blockade of the receptors. It seems that the rise of blood pressure takes place when the activity of alpha2-adrenoceptors is impared by the increased pressure of the balloon placed in the epidural space.