Title: intrathecal administered high-dose baclofen did not induce histological change in rats

Background: Intrathecal infusion of baclofen (ITB) therapy for spasticity was approved application of insuarance in Japan at 2006. Recently, ITB is reported to be analgesic effect for chronic pain 1, central pain 2, or CRPS 3 regardless of spasticity. However, there is only little information on baclofen-related neurotoxicity. Therefore, we examined intrathecal baclofen neurotoxicity by histological and neurofunctional analyses. 

Methods: Thirty-three rats were each randomly injected intrathecally with 0.12μl/g body weight of either of 400 (400B), 800 (800B), 2000 (2000B), 3000 (3000B), 4000 (4000B), or 8000 (8000B) μg/ml of baclofen dissolved in saline. Control rats received saline alone. Seven days after the injection, the L2 spinal cord with the anterior and posterior roots, dorsal ganglion, and cauda equina were extracted for microscopy. The hind limbs were evaluated neurologically by walking behavior.

Results: Neurohistopathological examination showed no evidence of neurotoxic damage in all groups. Immediately after intrathecal baclofen injection, all rats displayed lower limbs weakness, and couldn’t keep normal posture. However, all rats of each group could walk normally within 0.25, 0.25, 1, 1, 4, and 4h after injection in 400B, 800B, 2000B, 3000B, 4000B, and 8000B groups, respectively. None of the rats showed irreversible palsy or required tracheal intubation, even at 8000B. The sensory threshold was no significant difference among the baclofen and control groups at 7 days post-injection.

Discussion and Conclusion: Intrathecal baclofen produced no histological or neurofunctional neurotoxicity even at 8000B. Our previous studies on 4% bupivacaine neurotoxicity using the same experimental protocol showed nerve damage in rats, and posterior nerve lesions at concentrations approximately 8 times higher than the clinically-used concentration 4, while 8000B is approximately 50 times higher concentration than clinical concentration. These results indicate that intrathecal baclofen is a safe treatment option for chronic intractable pain. However, further investigation is necessary to determine the effects of continuous long-term infusion of baclofen. 
 
References:1.RAPM 2004;29:269  2.Anesthesiology 2000;92:876 3.RAPM 2002;27:90   4.RAPM 2005;30:464

Intrathecal administered high-dose baclofen did not induce histological change in rats