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Updated: May 6, 2026
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Morphologic features and glial activation in rat oxaliplatin-dependent neuropathic pain
Lorenzo Di Cesare Mannelli1, Alessandra Pacini, Laura Bonaccini
1Department of Neurosciences, Psychology, Drug Research and Child Health (Neurofarba), Pharmacology and Toxicology Section, University of Florence, Florence, Italy.
Unlabelled:
Neurotoxicity is the limiting side effect of the anticancer agent oxaliplatin. A tangled panel of symptoms, sensory loss, paresthesia, dysesthesia, and pain may be disabling for patients and adversely affect their quality of life. To elucidate the morphologic and molecular alterations that occur in the nervous system during neuropathy, rats were daily injected with 2.4 mg kg(-1) oxaliplatin intraperitoneally. A progressive decrease in the pain threshold and hypersensitivity to noxious and nonnoxious stimuli were evidenced during the treatment (7, 14, 21 days). On day 21, morphometric alterations were detectable exclusively in the dorsal root ganglia, whereas the activating transcription factor 3 and neurofilament (heavy-chain) expression changed dramatically in both the nerves and ganglia. Inflammatory features were not highlighted. Interestingly, satellite cells exhibited signs of activation. Glial modulation was characterized in the spinal cord and brain areas involved in pain signaling. On the 21st day, spinal astrocytes increased numerically whereas the microglial population was unaltered. The number of glial cells in the brain differed according to the zone and treatment time points. In particular, on day 21, a significant astrocyte increase was measured in the anterior cingulate cortex, somatosensory area 1, neostriatum, ventrolateral periaqueductal gray, and nucleus raphe magnus.
Perspectives:
These data highlight the relevance of glial cells in chemotherapy-induced neurotoxicity as part of the investigation of the role that specific brain areas play in neuropathy.
Insights
Oxaliplatin chemotherapy causes neurotoxicity, affecting nerves and dorsal root ganglia. Glial cells, particularly astrocytes in specific brain regions, play a key role in this chemotherapy-induced neuropathy.
Area of Science:
- Neuroscience
- Toxicology
- Oncology
Background:
- Oxaliplatin is a crucial chemotherapy drug for various cancers.
- Neurotoxicity is a significant dose-limiting side effect of oxaliplatin treatment.
- This neurotoxicity manifests as sensory loss, pain, and reduced quality of life.
Purpose of the Study:
- To investigate the morphologic and molecular changes in the nervous system during oxaliplatin-induced neuropathy in a rat model.
- To identify specific nervous system components and brain regions involved in oxaliplatin neurotoxicity.
Main Methods:
- Rats received daily intraperitoneal injections of oxaliplatin (2.4 mg/kg).
- Behavioral tests assessed pain threshold and hypersensitivity over 21 days.
- Morphometric analysis and gene expression (activating transcription factor 3, neurofilament heavy-chain) were performed on nerves and dorsal root ganglia.
- Glial cell populations (astrocytes, microglia) were quantified in the spinal cord and specific brain areas.
Main Results:
- Oxaliplatin treatment progressively reduced pain threshold and increased hypersensitivity.
- Morphometric alterations were observed in dorsal root ganglia by day 21.
- Activating transcription factor 3 and neurofilament (heavy-chain) expression increased in nerves and ganglia.
- Satellite cells in ganglia showed signs of activation.
- Spinal astrocytes increased numerically, while microglial populations remained unchanged.
- Specific brain areas, including the anterior cingulate cortex and somatosensory cortex, showed increased astrocyte numbers by day 21.
Conclusions:
- Glial cell modulation, especially astrocyte activation in pain-related brain areas, is central to oxaliplatin-induced neurotoxicity.
- These findings underscore the role of glial cells and specific brain regions in chemotherapy-induced neuropathy.
