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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Gabapentin prevents oxaliplatin-induced central sensitization in the dorsal horn neurons in rats
Teng Ruyang1, Zhao Yang1, Feng Wei1
1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao 266100, China.
Objectives:
The present study aims to study the alteration of glutamatergic transmission in the dorsal horn neurons and the effect of gabapentin on oxaliplatin-induced neuropathic pain in rats.
Materials And Methods:
Oxaliplatin (5 mg/kg) or saline was administered to adult male Sprague-Dawley rats. Gabapentin (60 mg/kg, IP) or vehicle was injected daily. Mechanical allodynia was assessed using a series of von Frey filaments. The expression of glutamate receptor subunits (NR2B and GluR1) and brain-derived neurotrophic factor (BDNF) was measured in the dorsal horn. The glutamatergic strength was recorded in the spinal cord slices.
Results:
Administration of oxaliplatin induced significant hyperreactivity to mechanical stimuli in rats, which was attenuated by gabapentin. Significant increase in the expression of BDNF was found in the dorsal horn in rats receiving oxaliplatin, which was prevented by gabapentin. Further studies also observed a significant increase in the expression of GluR1 and NR2B, as well as enhanced glutamatergic transmission in the dorsal horn neurons in rats treated with oxaliplatin. The upregulation of glutamatergic transmission was significantly reversed by gabapentin.
Conclusion:
These results illustrated an increased expression of BDNF and enhanced glutamatergic transmission in rats with oxaliplatin-induced neuropathic pain, which was markedly attenuated by gabapentin.
Insights
Gabapentin effectively treats oxaliplatin-induced neuropathic pain in rats by reducing mechanical allodynia. It normalizes increased brain-derived neurotrophic factor (BDNF) and glutamatergic transmission in dorsal horn neurons.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Oxaliplatin chemotherapy can cause neuropathic pain, characterized by hypersensitivity to stimuli.
- Glutamatergic transmission and brain-derived neurotrophic factor (BDNF) are implicated in pain signaling.
- Understanding these mechanisms is crucial for developing effective pain management strategies.
Purpose of the Study:
- To investigate alterations in glutamatergic transmission in the dorsal horn.
- To evaluate the efficacy of gabapentin in mitigating oxaliplatin-induced neuropathic pain in a rat model.
Main Methods:
- Oxaliplatin was administered to rats to induce neuropathic pain.
- Gabapentin or vehicle was administered daily to assess its therapeutic effect.
- Mechanical allodynia was measured, and dorsal horn tissue was analyzed for BDNF and glutamate receptor subunit expression (NR2B, GluR1).
- Glutamatergic transmission was recorded in spinal cord slices.
Main Results:
- Oxaliplatin induced significant mechanical hyperreactivity, which gabapentin attenuated.
- Oxaliplatin increased BDNF, GluR1, and NR2B expression and enhanced dorsal horn glutamatergic transmission.
- Gabapentin reversed these oxaliplatin-induced changes.
Conclusions:
- Oxaliplatin-induced neuropathic pain in rats is associated with increased BDNF and enhanced glutamatergic transmission.
- Gabapentin demonstrates significant therapeutic potential by attenuating these neurochemical alterations and pain behaviors.

