ANTINOCICEPTIVE EFFECT OF THE S(-ENANTIOMER OF KETAMINE ON CARRAGEENAN HYPERALGESIA AFTER INTRATHECAL ADMINISTRATION IN RATS())

Ketamine exerts antinociceptive effects in many pain tests. We investi gated the antinociceptive effect of intrathecally administered racemic ketamine and its S(+)- and R(-)-enantiomer on carrageenan-induced the rmal hyperalgesia with a paw withdrawal test and acute pain (hot plate and tailflick) tests. Rats were prepared with a chronic lumbar intrat hecal catheter to receive either saline or ketamine enantiomers in cum ulative doses. None of the ketamines (10, 50, or 100 mu g) had any eff ect on the withdrawal latency of the contralateral, noninjected paw. I n the injected paw, intrathecal saline did not alter carrageenan-induc ed thermal hyperalgesia, whereas intrathecally applied S(+)-, R(-)-, a nd racemic ketamine decreased thermal hyperalgesia. However, compared with saline, racemic ketamine had a higher efficacy than S(+)-ketamine , whereas R(-)-ketamine did not achieve statistical significance. Neit her S(+)- nor R(-)-ketamine had a significant effect in the tailflick test (10, 100, or 500 mu g). In the hot plate test, only the largest d ose of ketamine (500 mu g) caused a non-stereospecific, significant in crease in hot plate latency; this dose caused supraspinal effects as w ell. The results demonstrate that the behavioral hyperalgesia associat ed with carrageenan-induced hindpaw inflammation in rats is attenuated by the intrathecal administration of racemic and S(+)-ketamine, but n ot R(-)-ketamine, which only displayed an insignificant trend toward a dose-response relationship. This finding warrants further studies to investigate a possible clinical advantage of preservative-free S(+)-ke tamine over the currently used preservative containing racemic mixture . Implications: In rats, intrathecal S(+)-ketamine was effective for t reating inflammatory pain. Although racemic ketamine has a greater eff icacy, S(+)-ketamine is available as a preservative-free drug and migh t be of clinical interest for future neuraxial administration in diffe rent pain states.