INTRATHECAL INJECTION OF LYSINE ACETYLSALICYLIC-ACID IN THE RAT - A NEUROTOXICOLOGICAL STUDY

Lysine acetylsalicylic acid has been reported to induce analgesic effe cts in humans after intrathecal (i.t.) injection. Before conducting fu rther studies in humans with this drug, it is important to evaluate po tential toxicological effects on the spinal cord in animals. In the pr esent study the effects of chronic intrathecal administration of provo cative doses of lysine acetylsalicylic acid (L-ASA) on the rat spinal cord were evaluated using light and electron microscopy and a quantita tive morphometric method. We also investigated the effects of single d oses of the drug on the spinal cord blood flow (SCBF) using the laser- Doppler flowmetry technique. No histopathological changes or differenc es in number or density of neuronal cells could be seen after chronic administration of L-ASA as compared to controls. The SCBF decreased im mediately after i.t. injection of a large dose (4 mg) of L-ASA and ret urned to predrug levels within 10 min. At the end of the experiment me tabolic acidosis was detected, indicating a systemic effect of acetyls alicylic acid. It is concluded that no neurotoxic effects on the spina l cord were seen after chronic i.t. injection of L-ASA. From a neuroto xicological point of view, our findings do not contraindicate the spin al use of L-ASA in humans.