Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats

• Published in: Journal of neuroscience research Vol. 85; no. 11; pp. 2352 - 2359
• Main Authors: Gwak, Young Seob, Kang, Jonghoon, Leem, Joong Woo, Hulsebosch, Claire E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-08-2007
• Subjects: Animals; Axotomy; central neuropathic pain; Excitatory Amino Acid Antagonists - administration & dosage; Hindlimb - innervation; Injections, Spinal; Male; mechanical threshold; NBQX; Neuralgia - drug therapy; Neuralgia - etiology; Neuralgia - physiopathology; Physical Stimulation; Posterior Horn Cells - drug effects; Posterior Horn Cells - metabolism; Quinoxalines - administration & dosage; Rats; Rats, Sprague-Dawley; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - drug effects; Recovery of Function - drug effects; Spinal Cord Injuries - complications; Spinal Cord Injuries - physiopathology; spinal cord injury; WDR neurons
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21379

In this study, we examined whether a competitive AMPA receptor antagonist, NBQX, attenuates mechanical allodynia and hyperexcitability of spinal neurons in remote, caudal regions in persistent central neuropathic pain following spinal cord injury in rats. Spinal cord injury was produced by unilateral T13 transverse spinal hemisection, from dorsal to ventral, in male Sprague Dawley rats (200–250 g). Mechanical thresholds were measured behaviorally, and the excitability of wide‐dynamic‐range (WDR) dorsal horn neurons in the lumbar cord (L4–L5) was measured to assess central neuropathicpain. On postoperation day (POD) 28 after spinalhemisection, mechanical thresholds were significantly decreased in both injured (ipsilateral) and noninjured (contralateral) hindpaws compared with preinjury and sham control, respectively (P < 0.05). Intrathecal administration of NBQX (0.25, 0.5, 1 mM) significantly reversed the decreased mechanical thresholds in both hindpaws, dose dependently (P < 0.05). The excitability of WDR neurons was significantly enhanced on both sides of the lumbar dorsal horn 28 days following spinal hemisection (P < 0.05). The hyperexcitability of WDR neurons was attenuated by topical administration of NBQX (0.125, 0.25, 0.5, 1 mM), dose dependently (P < 0.05). Regression analysis indicated that at least three molecules of NBQX bond per receptor complex, and are needed to achieve inhibition of WDR hyperexcitability. In conclusion, our study demonstrates that the AMPA receptor plays an important role in behaviors related to the maintenance of central neuropathic pain below the level of spinal cord injury. © 2007 Wiley‐Liss, Inc.