Amitriptyline prevents thermal hyperalgesia and modifications in rat spinal cord GABA(B) receptor expression and function in an animal model of neuropathic pain.
Using an animal model of neuropathic pain, behavioral and biochemical experiments were performed to assess the effects of this condition on pain threshold and GABA(B) receptor sensitivity and subunit gene expression in the rat lumbar spinal cord. The results indicate that partial sciatic nerve ligation decreases thermal and mechanical pain withdrawal latencies, and increases baclofen-stimulated [35S]GTPgammaS binding and GABA(B) receptor subunit gene expression in the rat lumbar spinal cord, suggesting that neuropathic pain may be due, in part, to a deficiency in GABAergic transmission. The experiments also demonstrate that daily administration (10 mg/kg, i.p.) of amitriptyline, a tricyclic antidepressant used for the treatment of neuropathic pain, for 1 week after surgery prevents the decline in thermal pain threshold, the increase in GABA(B2) gene expression, and development of increased GABA(B) receptor function in spinal cord resulting from nerve damage. These findings indicate that the efficacy of amitriptyline as a treatment for neuropathic pain may be related to an ability to maintain spinal cord GABA(B) receptor activity.
McCarson
Kenneth E
KE
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 1018, Kansas City, KS 66160, USA.
Ralya
Andrew
A
Reisman
Scott A
SA
Enna
S J
SJ
D000639:Amitriptyline / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D006358:Hot Temperature; D006930:Hyperalgesia / Q000517:prevention & control*; D008297:Male; D017288:Pain Threshold; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism* / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D018080:Receptors, GABA-B; D000639:Amitriptyline