title: Site- and test-dependent antinociceptive efficacy of amitriptyline in rats.
abstract: The antinociceptive efficacy of systemic- (IV), spinal- (IT), and global supraspinal (ICV)-administered amitriptyline (AMIT) was compared in three different tests for nociception: the hot-plate test, the tail-flick test, and the withdrawal reflex test. Systemic AMIT inhibited the responses in each of the three tests, with distinct dose-effect relationships. Spinal AMIT reduced in a dose-dependent fashion the force of withdrawal to noxious electrical stimulation but was ineffective in the hot-plate test and facilitated the responses in the tail-flick test. Supraspinal AMIT inhibited in dose-dependent fashion the response to the stimulus of the hot plate, reduced the force of withdrawal after a dose that was effective by the IV route, and again facilitated the responses in the tail-flick test. The results suggest that spinal sites mediate the inhibition of the withdrawal reflex and the supraspinal site the inhibition of the hot-plate test. Two conclusion are drawn: First, AMIT's site of action varies among the pain modalities; and, second, augmentation of the reactions can occur. The complex interaction accords with the clinical experience that the benefits of AMIT in pain treatment are hard to predict.
authors.affiliation: Institute for Anesthesiology, University of Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Dirksen
authors.forename: D
authors.initials: D
authors.lastname: Van Diejen
authors.forename: E L
authors.initials: EL
authors.lastname: Van Luijtelaar
authors.forename: L H
authors.initials: LH
authors.lastname: Booij
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012879:Skin Physiological Phenomena
chemical_list: D000700:Analgesics; D000639:Amitriptyline