We studied whether striatal alpha₂-adrenoceptors contribute to regulation of pain-related behavior in neuropathic animals. Neuropathy was induced by ligation of two spinal nerves in the rat. Pain-related behavior was assessed by the monofilament test (tactile allodynia), paw pressure test (mechanical nociception and hyperalgesia) and the tail-flick test (thermal nociception). To assess excitability changes in the motor system, H-reflex was determined in the hind limb of lightly anesthetized animals. Fadolmidine, a selective alpha₂-adrenoceptor agonist, was microinjected via a chronic guide cannula into the dorsal striatum. Fadolmidine in the ipsi- but not contralateral striatum produced a dose-related attenuation of mechanical hypersensitivity in the neuropathic hind limb. When administered at a dose suppressing mechanical hypersensitivity, striatal fadolmidine had no significant effect on mechanical nociception in the non-injured hind limb, thermal nociception in the tail or the H-reflex in the ipsilateral hind limb. The tactile antiallodynic effect induced by fadolmidine in the striatum was attenuated by intrastriatal and systemic but not intrathecal administration of atipamezole, an alpha₂-adrenoceptor antagonist. Additionally, the tactile antiallodynic effect induced by striatal administration of fadolmidine was attenuated by intrastriatal or intrathecal administration of eticlopride, a dopamine D2 receptor antagonist, and intrathecal, but not intrastriatal, administration of WAY-10063, a 5-HT_1A receptor antagonist. The results indicate that activation of ascending noradrenergic pathways and a consequent activation of striatal alpha₂-adrenoceptors may selectively suppress neuropathic hypersensitivity via a circuitry involving striatal dopamine D2 receptors, descending serotoninergic and dopaminergic pathways and spinal 5-HT_1A and dopamine D2 receptors.