ROLE OF SATELLITE CELL-DERIVED L-SERINE IN THE DORSAL ROOT GANGLION IN PACLITAXEL-INDUCED PAINFUL PERIPHERAL NEUROPATHY

Paclitaxel is one of the most commonly used antineoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of L-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful peripheral neuropathy. Response to von Frey filaments, SNCV, 3-phosphoglycerate dehydrogenase (3PGDH) expression, and L-serine concentration were examined. Effects of L-serine administration were also investigated. Paclitaxel treatment induced mechanical allodynia/hyperalgesia and reduction of SNCV. Paclitaxel also decreased the L-serine concentration in the dorsal root ganglion (DRG) but not in the sciatic nerve or spinal cord. In addition, paclitaxel decreased expression of 3PGDH, a biosynthetic enzyme of L-serine, in the DRG. Immunohistochemistry showed that 3PGDH was localized in satellite cells but not in neurons in the DRG. Intraperitoneal administration of L-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived L-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.