Propentofylline’s Anti-Nociception Effect in a Rat Model of Vincristine-Induced Neuropathic Pain

Abstract

Background: A large proportion of cancer patients suffer from devastating neuropathic pain. Vincristine (Vin), a first-line anticancer therapy, usually induces this pain, which negatively affects the life quality of patients. Purpose: To explore propentofylline’s effect on Vin-induced neuropathic pain and its potential mechanism of action. Methods: A Vin-induced rat model was used in this study. Vin (125 µg/kg) was administered intraperitoneally every other day for 8 days (days 1~8), to establish neuropathic pain model in rats. Then, the rats were randomized into the model group and three treatment groups (low-, mid- and high-dosage groups). On days 8~14, the three treatment groups received daily intraperitoneal injections of propentofylline (PPF) at 6.25, 12.5, and 25 mg/kg/day, while all groups received equal volumes of physiological saline. Behavioral tests were conducted, to check pain hypersensitivity on days 0, 8, 10, 14 and 21. Glial activation was assessed using immunohistochemical method on day 14. Spinal cord pro-inflammatory cytokines and chemokine levels were estimated using enzyme-linked immunosorbent assay (ELISA) on days 8, 14 and 21. Results: Vin-induced pain hypersensitivity was significantly suppressed by mid-dosage and high-dosage PPF treatment, starting from day 10 (p < 0.05 or 0.01). On day 14, activated glial numbers decreased significantly on mid- and high-dosage PPF treatments (p < 0.05 or 0.01). High-dosage PPF treatment significantly reduced MCP-1 (monocyte chemoattractant protein-1) up-regulation (p < 0.01). The up-regulation of pro-inflammatory cytokines were significantly reduced by mid-dosage and high-dosage PPF (p < 0.01 or 0.05). Conclusions: Neuroinflammation plays a crucial role in the progression of Vin-induced neuropathic pain. PPF could attenuate this pain, through weakening the recruitment of neuroinflammation, thereby relieving pain hypersensitivity in rat.