Sensory neurons and their supporting cells located in the trigeminal, thoracic and lumbar ganglia differentially express markers of injury following intravenous administration of paclitaxel in the rat

Neurosci Lett. 2006 Sep 11;405(1-2):62-7. doi: 10.1016/j.neulet.2006.06.043. Epub 2006 Jul 18.


Paclitaxel-induced peripheral neuropathy is a sensory neuropathy that affects thousands of cancer patients each year as paclitaxel is commonly used to treat breast, non-small cell lung and ovarian cancer. To begin to define the type and location of sensory neurons most impacted by paclitaxel, we examined rat trigeminal ganglion, thoracic and lumbar dorsal root ganglion (DRG) 10 days following intravenous infusion of clinically relevant doses of paclitaxel. To define the population of cells injured by paclitaxel, we examined the expression of activating transcription factor-3 (ATF3), a marker of cell injury; to define the hypertrophy of satellite cells, we quantified the expression of the intermediate filament protein glial fibrillary acidic protein (GFAP); and to define the activation of macrophages, we examined the expression of the lysosomal protein CD68. Intravenous infusion of paclitaxel induced a significant increase of ATF3 in mainly but not exclusively large and medium sensory neurons in all sensory ganglia. An increase in both GFAP immunofluorescence in satellite cells and the number of activated macrophages occurred in lumbar>thoracic>trigeminal ganglia of paclitaxel-treated rats. This differential expression of cellular markers suggests that the largest sensory cell bodies with the longest axons are the most at risk of being injured by paclitaxel (size and length dependent pathology). These results provide a pathological basis for the anatomical distribution of paclitaxel-induced symptoms in patients receiving therapeutic regimens of paclitaxel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Activating Transcription Factor 3 / biosynthesis
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Biomarkers / metabolism
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Glial Fibrillary Acidic Protein / biosynthesis
  • Injections, Intravenous
  • Lumbosacral Region
  • Male
  • Neurons, Afferent / drug effects*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects*
  • Pain / chemically induced
  • Pain / metabolism
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Thorax
  • Trigeminal Ganglion / drug effects*
  • Trigeminal Ganglion / metabolism


  • Activating Transcription Factor 3
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents, Phytogenic
  • Atf3 protein, rat
  • Biomarkers
  • CD68 antigen, human
  • Glial Fibrillary Acidic Protein
  • Paclitaxel