Program

PO2-2-28

To study the anti-hyperalgesic and anti-allodynic effects of Atorvastatin and Low Dose Naltrexone in Vincristine Induced Peripheral Neuropathic Pain Model in Rats

[Speaker] Saniya Mahendiratta:1
[Co-author] Amitava Chakrabarti:1, Debasish Hota:2
1:Pharmacology, PGIMER, India, 2:Department of Pharmacology, AIIMS, Bhubneshwar, India

Background: Peripheral neuropathy is a common adverse effect of anticancer drugs like vincristine and paclitaxel. Current pharmacotherapy for this type of neuropathic pain is unsatisfactory.

Aim: To evaluate the efficacy of atorvastatin and low dose naltrexone in vincristine induced neuropathic pain model in rats.

Methodology: 7 groups of male Wistar rats were administered vincristine (0.05mg/kg, 1-10 days) i.p, for the development of neuropathic pain (includes 1 positive control) and 1 group was given saline (negative control). Atorvastatin (1 and 2 mg/kg), low dose naltrexone (0.2 and 0.5 mg/kg) and two drug combinations of different doses were given on 12-15 days to vincristine groups. The efficacy was evaluated by tail flick, tail cold allodynia, hot water tail immersion and cold nociceptive sensitivity methods on day 16th, 23th and 30th.

Results: All the rats treated with vincristine developed Peripheral Neuropathy by day 12. It was evidenced by a rapid decline in nociceptive threshold and development of hyperalgesia and allodynia. Atorvastatin (1 and 2 mg/kg) and low dose naltrexone (0.2 and 0.5 mg/kg) showed significant improvement in heat hyperalgesia and cold allodynia on day 16 and 23 (p<0.05). There was also a significant increase in the tail flick latency and paw withdrawal response. (p<0.05). The combination of atorvastatin (1 mg/kg) and low dose naltrexone (0.2 and 0.5 mg/kg) were also evaluated using above parameters and showed significant anti-hyperalgesic and anti-allodynic effects on day 16th and 23th compared to the active control (p<0.05). No significant difference was observed in the combination therapy from single drug responses.

Conclusion: Atorvastatin and low dose naltrexone were effective in neuropathic pain models and should be further evaluated for chemotherapy induced neuropathy.

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