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Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells.
Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells.
- Source :
-
Experimental neurology [Exp Neurol] 2007 Jan; Vol. 203 (1), pp. 42-54. Date of Electronic Publication: 2006 Sep 26. - Publication Year :
- 2007
-
Abstract
- Paclitaxel-induced peripheral neuropathy (PN) can be a significant problem for patients receiving chemotherapeutic regimens for the treatment of breast, ovarian, and lung cancer as PN can influence the quality of life and survivorship in these patients. To begin to understand the cellular changes that occur within the peripheral and central nervous system as PN develops, we intravenously infused rats with clinically relevant doses of paclitaxel. Ten days later, behavioral changes indicative of PN became evident that included mechanical allodynia, cold hyperalgesia, and deficits in ambulation/coordination. These behaviors were accompanied by increased expression of activating transcription factor 3 (ATF3; a marker of cellular injury) in a population of large>medium>small diameter sensory neurons, a population of satellite cells in the lumbar dorsal root ganglia (DRG) and in myelinating Schwann cells in the sciatic nerve. In addition, there was an increase in the expression of glial fibrillary acidic protein (GFAP) in DRG satellite cells and an increase in the number of CD68 positive activated macrophages within the DRG and peripheral nerve. Within lamina III-IV of the lumbar spinal cord, there was an increase in OX42 positive microglia. These data suggest that intravenous infusion of paclitaxel induces a peripheral neuropathy characterized by injury of neuronal and non-neuronal cells in the peripheral nervous system, macrophage activation in both the DRG and peripheral nerve, and microglial activation within the spinal cord. An understanding of the factors involved in the development and maintenance of PN may lead to mechanism based therapies that prevent/treat PN and thus improve the survival and quality of life of patients receiving chemotherapy.
- Subjects :
- Activating Transcription Factor 3 drug effects
Activating Transcription Factor 3 metabolism
Animals
Antigens, CD drug effects
Antigens, CD metabolism
Antigens, Differentiation, Myelomonocytic drug effects
Antigens, Differentiation, Myelomonocytic metabolism
Antineoplastic Agents, Phytogenic toxicity
CD11b Antigen
Chemotaxis, Leukocyte physiology
Disease Models, Animal
Ganglia, Spinal drug effects
Ganglia, Spinal metabolism
Ganglia, Spinal pathology
Glial Fibrillary Acidic Protein drug effects
Glial Fibrillary Acidic Protein metabolism
Hyperalgesia chemically induced
Hyperalgesia pathology
Hyperalgesia physiopathology
Injections, Intravenous
Macrophages metabolism
Male
Microglia drug effects
Microglia metabolism
Microglia pathology
Neurons, Afferent metabolism
Neurons, Afferent pathology
Peripheral Nerves pathology
Peripheral Nerves physiopathology
Peripheral Nervous System Diseases pathology
Peripheral Nervous System Diseases physiopathology
Posterior Horn Cells drug effects
Posterior Horn Cells metabolism
Posterior Horn Cells pathology
Rats
Rats, Sprague-Dawley
Satellite Cells, Perineuronal drug effects
Satellite Cells, Perineuronal metabolism
Satellite Cells, Perineuronal pathology
Schwann Cells drug effects
Schwann Cells metabolism
Schwann Cells pathology
Chemotaxis, Leukocyte drug effects
Macrophages drug effects
Neurons, Afferent drug effects
Paclitaxel toxicity
Peripheral Nerves drug effects
Peripheral Nervous System Diseases chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4886
- Volume :
- 203
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 17005179
- Full Text :
- https://doi.org/10.1016/j.expneurol.2006.07.022