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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Gabapentin prevents oxaliplatin-induced mechanical hyperalgesia in mice
Masahiro Ohsawa1, Saki Otake, Tomoyasu Murakami
1Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan.
Abstract:
Oxaliplatin, a platinum-based chemotherapy drug, frequently causes acute and chronic peripheral neuropathies including mechanical hyperalgesia. These adverse effects hinder anticancer therapy with the drug. In this study, we examined several drugs that might prevent oxaliplatin-induced peripheral neuropathy. Single intraperitoneal (i.p.) injection of oxaliplatin (10 mg/kg) induced cold allodynia (acetone test) and mechanical hyperalgesia (von Frey test). Gabapentin, but not simvastatin and atorvastatin, prevented oxaliplatin-induced mechanical hyperalgesia without affecting cold allodynia. Moreover, oxaliplatin caused phosphorylation of cofilin protein in the spinal cord, which has been shown to be involved in the neuropathic hyperalgesia. This increased phosphorylation of cofilin was also attenuated by gabapentin treatment. These results suggest that gabapentin is useful for relieving oxaliplatin-induced mechanical hyperalgesia and that the pathogenic mechanisms of cold allodynia and mechanical hyperalgesia differ.
Insights
Gabapentin effectively prevents oxaliplatin-induced mechanical hyperalgesia, a common chemotherapy side effect. This study highlights gabapentin
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Oxaliplatin, a platinum-based chemotherapy, frequently induces peripheral neuropathies, impacting cancer treatment efficacy.
- Oxaliplatin-induced neuropathies manifest as acute and chronic pain, including mechanical hyperalgesia and cold allodynia.
Purpose of the Study:
- To investigate potential therapeutic agents for preventing oxaliplatin-induced peripheral neuropathy.
- To evaluate the efficacy of gabapentin, simvastatin, and atorvastatin in mitigating oxaliplatin-induced pain.
Main Methods:
- Oxaliplatin was administered via intraperitoneal injection to induce neuropathy in a preclinical model.
- Mechanical hyperalgesia and cold allodynia were assessed using von Frey and acetone tests, respectively.
- Spinal cord cofilin protein phosphorylation was analyzed to understand underlying molecular mechanisms.
Main Results:
- Gabapentin significantly prevented oxaliplatin-induced mechanical hyperalgesia but did not affect cold allodynia.
- Simvastatin and atorvastatin did not show efficacy in preventing oxaliplatin-induced neuropathic pain.
- Oxaliplatin-induced cofilin phosphorylation in the spinal cord was reduced by gabapentin treatment.
Conclusions:
- Gabapentin demonstrates therapeutic potential for managing oxaliplatin-induced mechanical hyperalgesia.
- The findings suggest distinct pathogenic pathways for mechanical hyperalgesia and cold allodynia in oxaliplatin neuropathy.
