Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions.
Central pain syndrome (CPS) is defined as pain associated with a lesion of the CNS and is a common consequence of spinal cord injuries. We generated a rodent model of CPS by making unilateral electrolytic or demyelinating lesions centered on the spinothalamic tract in rats. Thermal hyperalgesia and mechanical allodynia occurred in both hind paws and forepaws by 7 d postlesion and were maintained >31 d. Field potentials in the ventral posterior lateral nucleus (VPL) in thalamic brain slices from lesioned animals displayed an increased probability of burst responses. Ethosuximide, a T-type calcium channel blocker, eliminated busting in lesioned thalamic slices and attenuated lesion-induced hyperalgesia and allodynia. We conclude that CPS in this model results from an increase in the excitability of thalamic nuclei that have lost normal ascending inputs as the result of a spinal cord injury and suggest that ethosuximide will relieve human CPS by restoring normal thalamic excitability.
Wang
Gexin
G
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. gwang003@umaryland.edu
Thompson
Scott M
SM
D000200:Action Potentials / Q000502:physiology; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism; D002422:Causalgia / Q000209:etiology / Q000503:physiopathology*; D003714:Denervation; D004195:Disease Models, Animal; D005013:Ethosuximide / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D010148:Intractable Pain / Q000209:etiology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D013133:Spinothalamic Tracts / Q000276:immunology / Q000503:physiopathology*; D013577:Syndrome; D013788:Thalamus / Q000503:physiopathology*; D020651:Ventral Thalamic Nuclei / Q000503:physiopathology
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D005013:Ethosuximide