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Anti-allodynic effects following intrathecal administration of α1- and α2-adrenergic receptor agonists in a rat model of trigeminal neuropathic pain

Kunihiro Nakai, Aya Nakae, Sosuke Oba, Ko Hosokawa, Takashi Mashimo, Koichi Ueda


The descending noradrenergic system inhibits nociception in the spinal cord. Spinal nerve injury triggers ectopic sprouting of sympathetic nerve fibers within dorsal root ganglia. Spinal α2-adrenoceptors, but not α1-adrenoceptors, exert an inhibitory effect in a rat model of spinal nerve ligation. However, trigeminal nerve injury does not induce sprouting of sympathetic nerve fibers in the trigeminal ganglion. In the present study, we analyzed the roles of α1- and α2-adrenoceptors in anti-allodynic effects following trigeminal nerve injury.

Chronic constriction injury to the infraorbital nerve (ION-CCI) with loose ligatures was used to establish a trigeminal neuropathic pain model. Allodynia was evaluated by applying von Frey filaments. The anti-allodynic effects after intrathecal administration of α1- and α2-adrenoceptor agonists and antagonists were examined.

Administration of the α1-adrenoceptor agonist phenylephrine (3, 10, and 30 μg) and α2-adrenoceptor agonist clonidine (3, 10, and 30 μg) resulted in dose-dependent anti-allodynic effects. Intrathecal administration of the α1-adrenoceptor antagonist prazosin (30 μg) and α2-adrenoceptor antagonist yohimbine (30 μg) did not alter the mechanical thresholds. Intrathecal pretreatment with prazosin (3 and 10 μg) reduced the anti-allodynic effects of the highest phenylephrine dose, while intrathecal pretreatment with yohimbine (3 and 10 μg) reduced the anti-allodynic effects of the highest clonidine dose.

Peripheral adrenergic modulation following nerve injury did not aggravate trigeminal neuropathic pain. These results differ from a previous rat neuropathic pain model of spinal nerve injury. In the ION-CCI rat model, the spinal α1- and α2-adrenoceptors played roles in spinal inhibition of trigeminal neuropathic pain.


infraorbital nerve, trigeminal nerve, α1- and α2-adrenergic receptor, orofacial neuropathic pain, nerve injury, sympathetic sprouting

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DOI: http://dx.doi.org/10.18103/mra.v2i3.387


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