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 anti-neoplastic 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.
Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
T
T
Kiya
T
T
Kawamata
A
A
Namiki
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M
Yamakage
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009431:Neural Conduction; D017239:Paclitaxel / Q000009:adverse effects*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D050543:Phosphoglycerate Dehydrogenase / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D027161:Satellite Cells, Perineuronal / Q000378:metabolism*; D012694:Serine / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013623:Tail / Q000294:innervation; D014110:Touch
D000972:Antineoplastic Agents, Phytogenic; D012694:Serine; D050543:Phosphoglycerate Dehydrogenase; D017239:Paclitaxel