Intrathecal injection of lysine acetylsalicylic acid in the rat: a neurotoxicological study.
Lysine acetylsalicylic acid has been reported to induce analgesic effects in humans after intrathecal (i.t.) injection. Before conducting further studies in humans with this drug, it is important to evaluate potential toxicological effects on the spinal cord in animals. In the present study the effects of chronic intrathecal administration of provocative doses of lysine acetylsalicylic acid (L-ASA) on the rat spinal cord were evaluated using light and electron microscopy and a quantitative morphometric method. We also investigated the effects of single doses of the drug on the spinal cord blood flow (SCBF) using the laser-Doppler flowmetry technique. No histopathological changes or differences in number or density of neuronal cells could be seen after chronic administration of L-ASA as compared to controls. The SCBF decreased immediately after i.t. injection of a large dose (4 mg) of L-ASA and returned to predrug levels within 10 min. At the end of the experiment metabolic acidosis was detected, indicating a systemic effect of acetylsalicylic acid. It is concluded that no neurotoxic effects on the spinal cord were seen after chronic i.t. injection of L-ASA. From a neurotoxicological point of view, our findings do not contraindicate the spinal use of L-ASA in humans.
Svensson
B A
BA
Department of Anatomy, Uppsala University, Sweden.
Karlsten
R
R
Kristensen
J D
JD
Sottile
A
A
Bennett
A
A
Gordh
T
T
D000700:Analgesics / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007278:Injections, Spinal; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects*
D000700:Analgesics; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate