The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries.
Summary of "The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries."
Painful peripheral neuropathies produced by nerve trauma are accompanied by substantial axonal degeneration and by a response in spinal cord microglia that is characterized by hypertrophy and increased expression of several intracellular and cell-surface markers, including ionizing calcium-binding adapter molecule 1 (Iba1) and Cd11b (a complement receptor 3 antigen recognized by the OX42 antibody). The microglia response has been hypothesized to be essential for the pathogenesis of the neuropathic pain state. In contrast, the painful peripheral neuropathies produced by low doses of cancer chemotherapeutics do not produce degeneration of axons in the peripheral nerve, although they do cause partial degeneration of the sensory axons' distal-most tips, that is the intraepidermal nerve fibers that form the axons' terminal receptor arbors. The question thus arises as to whether the relatively minor and distal axonal injury characterizing the chemotherapy-evoked neuropathies is sufficient to evoke the microglial response that is seen after traumatic nerve injury. We examined the lumbar spinal cord of rats with painful peripheral neuropathies due to the anti-neoplastic agents, paclitaxel, vincristine, and oxaliplatin, and the anti-retroviral agent, 2',3'-dideoxycytidine (ddC), and compared them to rats with a complete sciatic nerve transection and the partial sciatic nerve injury produced in the chronic constriction injury model (CCI). As expected, microglia hypertrophy and increased expression of Iba1 were pronounced in the nerve transection and CCI animals. However, there was no microglia hypertrophy or increased Iba1 staining in the animals treated with paclitaxel, vincristine, oxaliplatin, or ddC. These results suggest that the mechanisms that produce neuropathic pain after exposure to chemotherapeutics may be fundamentally different than those operating after nerve trauma.
Affiliation
Department of Anesthesia, McGill University, Montréal, QC, Canada.
Journal Details
This article was published in the following journal.
Name: Neuroscience
ISSN: 1873-7544
Pages: 447-54
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21195745
- DOI: http://dx.doi.org/10.1016/j.neuroscience.2010.12.052
Medical and Biotech [MESH] Definitions
Evoked Potentials, Somatosensory
The electric response evoked in the CEREBRAL CORTEX by stimulation along AFFERENT PATHWAYS from PERIPHERAL NERVES to CEREBRUM.
Audiometry, Evoked Response
A form of electrophysiologic audiometry in which an analog computer is included in the circuit to average out ongoing or spontaneous brain wave activity. A characteristic pattern of response to a sound stimulus may then become evident. Evoked response audiometry is known also as electric response audiometry.
Evoked Potentials
The recorded electrical responses from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Often used synonymously to event-related potentials which are associated with higher level cognitive processes.
Evoked Potentials, Auditory
The electric response evoked in the CEREBRAL CORTEX by ACOUSTIC STIMULATION or stimulation of the AUDITORY PATHWAYS.
Early Growth Response Protein 2
An early growth response transcription factor that controls the formation of the MYELIN SHEATH around peripheral AXONS by SCHWANN CELLS. Mutations in EGR2 transcription factor have been associated with HEREDITARY MOTOR AND SENSORY NEUROPATHIES such as CHARCOT-MARIE-TOOTH DISEASE.
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