Journal of Pain Research (Feb 2020)
The Antiallodynic Effect of Nefopam on Vincristine-Induced Neuropathy in Mice
Abstract
Jin Young Lee,1 Woo Seog Sim,1 Noo Ree Cho,2 Bae Wook Kim,2 Jeong Yeon Moon,2 Hue Jung Park2 1Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Korea; 2Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, College of Medicine, Seoul, KoreaCorrespondence: Hue Jung ParkDepartment of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaTel +82 2-2258-6157Fax +82 2-537-1951Email [email protected]: Chemotherapy-induced neuropathic pain is a disabling condition following cancer treatment. Vincristine has more neurotoxicity than other vinca alkaloid agents. This study evaluated the correlation of different doses of nefopam with antiallodynic effects in a mouse vincristine neuropathy model.Methods: A peripheral neuropathic mouse model was made by intraperitoneal injection of vincristine (0.1 mg/kg/day; 5-day-on, 2-day-off schedule over 12 days). After the development of allodynia, mice were injected intraperitoneally with 0.9% normal saline (NS group) or various doses (10, 30, 60 mg/kg) of nefopam (Nefopam group). We examined allodynia using von Frey hairs pre-administration and at 30, 60, 90, 120, 180, 240 mins, and 24 hrs after drug administration. We also measured the neurokinin-1 receptor concentrations in the spinal cord to confirm the antiallodynic effect of nefopam after drug administration.Results: The peripheral neuropathic mouse model showed prominent mechanical allodynia. Intraperitoneal nefopam produced a clear dose-dependent increase in paw withdrawal threshold compared with pre-administration values and versus the NS group. The concentration of neurokinin-1 receptor was significantly decreased in the Nefopam group (P< 0.05).Conclusion: Intraperitoneally administered nefopam yielded a dose-dependent attenuation of mechanical allodynia and decreased neurokinin-1 receptor concentration, suggesting that the neurokinin-1 receptor is involved in the antiallodynic effects of nefopam in vincristine neuropathy.Keywords: allodynia, mice, nefopam, neurokinin-1, neuropathy, vincristine
