Tianeptine Reduces Mechanical Allodynia in Spinal Nerve-ligated and Chemotherapyinduced Neuropathic Mice

Background: Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits structural similarities to tricyclic antidepressants but has distinct neurochemical properties. Objective: Here we examined the effects of intraperitoneal (i.p.) tianeptine on allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice. Study Design: A randomized, experimental trial. Setting: Laboratory animal study. Methods: Spinal nerve-ligated neuropathy was induced in a Chung model made by ligating the L5 spinal nerve. Chemotherapy-induced neuropathy was induced by injecting vincristine (0.1 mg/kg/day; i.p.) on the following schedule: 5 days on, 2 days off, for14 days. Tianeptine (10, 30, and 50 mg/kg) and saline were administered, respectively, to both groups of neuropathic mice (n = 5 for each group). We evaluated mechanical allodynia using von Frey hairs prior to drug injections and at 30, 60, 90, 120, 180, and 240 minutes, and 24 hours after injections. We also measured the changes in activate transcription factor 3 (ATF3) level in the dorsal root ganglion (DRG) in each group in order to understand the analgesic mechanism of tianeptine. Results: Both spinal nerve-ligated and chemotherapy-induced neuropathic mice showed prominent allodynia. The control group showed no differences in mechanically induced allodynia compared to the experimental groups. For the tianeptine groups, paw-withdrawal thresholds in response to mechanical stimuli were significantly lower than the pre-administration values and values from the control group (P < 0.05). The increase in DRG ATF3 in neuropathic mice was reduced by tianeptine (P < 0.05). Limitations: Less is known about the transcription factors that affect inflammation signaling. Conclusions: Tianeptine administered i.p. reduces mechanical allodynia in spinal nerveligated and chemotherapy-induced neuropathic mice models. These effects were confirmed by attenuation of previously increased DRG ATF3. Key words: Tianeptine, spinal-nerve ligation, chemotherapy-induced neuropathic, activating transcription factor 3