Suppressive effect of imipramine on vincristine-induced mechanical allodynia in mice.
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 lambda-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.
Saika
Fumihiro
F
Department of Pharmacology, Wakayama Medical University.
Kiguchi
Norikazu
N
Kobayashi
Yuka
Y
Fukazawa
Yohji
Y
Maeda
Takehiko
T
Ozaki
Masanobu
M
Kishioka
Shiroh
S
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007099:Imipramine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D010147:Pain Measurement; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000517:prevention & control*; D014750:Vincristine / Q000009:adverse effects*
D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D009020:Morphine; D007099:Imipramine