Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury.

Abstract

Spinal cord injuries (SCI) result in a devastating loss of function and chronic central pain syndromes frequently develop in the majority of these patients. The present study uses a rodent spinal hemisection model of SCI in which mechanical and thermal allodynia develops by 24 days after injury. Post-operative paw withdrawal responses to low threshold and high threshold mechanical stimuli compared to pre-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (p<0.05) for both forelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal accompanied by paw lick occurred was significantly decreased (p<0.05), indicating the development of thermal allodynia. The intrathecal application of either D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the mechanical allodynia and lowered the threshold of response for the high threshold mechanical stimuli in a dose-dependent manner, and these decreases were statistically significant (p<0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodynia behavior in either forelimbs or hindlimbs in the hemisected group. No significant changes in locomotion scores, and thus no sedation, were demonstrated by the hemisected group for the doses tested. These data support the potential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain, particularly where input from low threshold mechanical afferents trigger the onset of the painful sensation. Furthermore, these data suggest a role for both NMDA and non-NMDA receptors in the development of plastic changes in the spinal cord that provide the underlying mechanisms for central neuropathic pain.

• Authors: A D Bennett, A W Everhart, C E Hulsebosch
• Journal: Brain research (Brain Res) Vol. 859 Issue 1 Pg. 72-82 (Mar 17 2000) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10720616 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Excitatory Amino Acid Antagonists
• Quinoxalines
• Receptors, N-Methyl-D-Aspartate
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• 2-amino-5-phosphopentanoic acid
• Valine

Topics

• Animals
• Chronic Disease
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Antagonists (pharmacology)
• Hyperalgesia (drug therapy, physiopathology)
• Injections, Spinal
• Male
• Motor Activity (physiology)
• Pain (drug therapy, physiopathology)
• Physical Stimulation
• Quinoxalines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects, physiology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Spinal Cord (drug effects, physiopathology, surgery)
• Spinal Cord Injuries (drug therapy, physiopathology)
• Valine (analogs & derivatives, pharmacology)