Intrathecally administered perampanel alleviates neuropathic and inflammatory pain in rats

Abstract

Chronic pain conditions such as neuropathic pain and persistent inflammatory pain are difficult to manage. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate nociceptive processing at the spinal dorsal horn. Previous studies have shown that intrathecal AMPA receptor antagonists exert antinociception in various pain states. Perampanel is a selective, noncompetitive inhibitor of the AMPA receptor and used clinically as an antiepileptic drug. Little is known about antinociceptive action of perampanel in the spinal cord. Here, we explored whether intrathecal perampanel attenuates neuropathic and inflammatory pain. A chronic constriction injury (CCI) to the sciatic nerve was induced in male Sprague-Dawley rats. We evaluated the effects of intrathecal perampanel (10, 30, or 100 μg) on mechanical and cold hyperalgesia using the electronic von Frey and cold plate tests, respectively. Normal rats were assessed in terms of inflammatory nociception using the formalin test, and motor function employing the rotarod test. In the CCI rats, spinally applied perampanel inhibited mechanical and cold hyperalgesia dose-dependently. In normal rats, perampanel remarkably suppressed the early- and late-phase responses in the formalin test, and it weakly affected motor performance for a short period at the highest dose. These results suggest that perampanel exerts antinociceptive actions on neuropathic and persistent inflammatory pain in the spinal cord. Perampanel may be safe and beneficial remedy for patients with such pain conditions. In addition, AMPA receptor can be a promising target for treatment of chronic pain.