Role of satellite cell-derived L-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

Neuroscience. 2011 Feb 3;174:190-9. doi: 10.1016/j.neuroscience.2010.11.046. Epub 2010 Nov 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Cold Temperature
  • Ganglia, Spinal / metabolism*
  • Hyperalgesia / chemically induced
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Male
  • Neural Conduction
  • Paclitaxel / adverse effects*
  • Pain / chemically induced
  • Pain / metabolism*
  • Pain / physiopathology
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / metabolism*
  • Peripheral Nervous System Diseases / physiopathology
  • Phosphoglycerate Dehydrogenase / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Satellite Cells, Perineuronal / metabolism*
  • Serine / biosynthesis*
  • Serine / chemistry
  • Serine / pharmacology
  • Stereoisomerism
  • Tail / innervation
  • Touch


  • Antineoplastic Agents, Phytogenic
  • Serine
  • Phosphoglycerate Dehydrogenase
  • Paclitaxel