perampanel and Neuralgia

¿Existe evidencia científica para el empleo de perampanel en el dolor neuropático?

Topics: Humans; Neuralgia; Nitriles; Pyridones

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.

Topics: Animals; Chronic Pain; Disease Models, Animal; Humans; Injections, Spinal; Male; Neuralgia; Nitriles; Nociception; Peripheral Nerve Injuries; Pyridones; Rats; Receptors, AMPA; Sciatic Nerve; Spinal Cord

The present study explores the pain attenuating effect of perampanel, AMPA receptor antagonist, in chronic constriction injury-induced neuropathic pain. Chronic Constriction Injury was performed by putting four loose ligatures around the sciatic nerve. Pain was assessed by determining mechanical hyperalgesia, cold allodynia and heat hyperalgesia on 7th and 14th day post surgery. Perampanel (3mg and 6mg/kg, p.o.) was administered 30min before pain assessment test on 14th day post-surgery. CCI led to significant development of pain and peak symptoms were observed on 14th day. Perampanel significantly attenuated CCI-induced mechanical hyperalgesia, cold allodynia and heat hyperalgesia, at different time intervals 30, 60, 90, 120min, with more substantial effect observed at dose of 6mg/kgNaloxone was administered in CCI subjected rats before perampanel treatment to explore the potential role of opioids in anti-nociceptive effects of perampanel. Naloxone decreased the pain attenuating effects of perampanel significantly, indicating a critical role of opioid system in anti-nociceptive potential of perampanel. Perampanel has pain attenuating potential in CCI-induced neuropathic pain, which may be due to partly mediated through the opioid system.

Topics: Animals; Chronic Disease; Constriction; Disease Models, Animal; Female; Hyperalgesia; Male; Motor Activity; Naloxone; Neuralgia; Nitriles; Pyridones; Rats, Wistar