Suppressive Effect of Imipramine on Vincristine-Induced Mechanical Allodynia in Mice

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Because chronic vincristine (VCR) treatment causes neuropathic pain, as demonstrated by mechanical allodynia, effective therapeutic strategy is required. In this study, we investigated a suppressive effect of imipramine (IMI) on VCR-induced mechanical allodynia in mice. VCR (0.1 mg/kg, intraperitoneally (i.p.)) was administered once per day for 7 d in ICR male mice. Mechanical allodynia was evaluated by withdrawal response using von Frey filaments. In VCR-treated mice, mechanical allodynia was observed on day 3, 7, and 14. On day 14, morphine (3 mg/kg, subcutaneously) slightly but significantly suppressed VCR-induced mechanical allodynia. The percent inhibition by morphine of VCR-induced mechanical allodynia was less than that of the λ-carrageenan-induced inflammatory pain and was similar to that of nerve injury-induced neuropathic pain. Although single administration of IMI (30 mg/kg, i.p.) had no effect on VCR-induced mechanical allodynia, repeated administration of IMI (30 mg/kg, i.p.) for 7 d significantly suppressed VCR-induced mechanical allodynia. Suppressive effects by repeated IMI administration were observed in both early phase (day 0—6) and late phase (day 7—13) of VCR-induced mechanical allodynia. These results suggest that chronic VCR administration induces opioid analgesics-resistant mechanical allodynia, and repeated IMI administration may be an effective therapeutic approach for the treatment of VCR-induced mechanical allodynia.