జర్నల్ ఆఫ్ పెయిన్ & రిలీఫ్

నైరూప్య

Effect of Tianeptine on Spared Nerve Injury-Induced Allodynia and Prefrontal Cortex Vascular Endothelial Growth Factor

Alex V Trevino, Steven A Castillo, Candelaria C Daniels, John L Clifford, Kenney H Wells, Thomas Stark, Bopaiah P Cheppudira

Objectives: Antidepressant drugs are widely used in the management of neuropathic pain. Emerging studies have shown that tianeptine (TNT), an atypical antidepressant with distinct neurochemical properties, is effective in reducing neuropathic pain symptoms. However, the neural mechanisms underlying the analgesic action of TNT are not fully understood. Alteration in vascular endothelial growth factor (VEGF) expression appears to play an important role in both pain and antidepressant mechanisms. Although the involvement of VEGF in inflammatory or neuropathic pain at the spinal level has been reported, the effect of neuropathic pain on cortex VEGF is unknown. Additionally, the TNT effect on cortex VEGF is not reported. The present study examined changes in cortex VEGF levels following TNT treatment in the neuropathic pain state.

Methods: The experiments were performed in a rat model of spared nerve injury (SNI)-induced neuropathic pain. TNT (75 mg/60 kg/day/orally) or saline was administered to SNI rats on days 14-18 post-injury. The effects of TNT on SNI-induced mechanical and cold allodynia were assessed by von Frey and acetone drop tests, respectively. The changes in the prefrontal cortex (PFC) VEGF protein expression following SNI and TNT treatments were measured by a Simple Western automated system.

Results: Rats that underwent the SNI protocol displayed both mechanical and cold allodynia, as expected. Single and repeated administration of TNT significantly reduced mechanical allodynia but had no effect on cold allodynia. Additionally, SNI rats showed increased VEGF protein expression in the PFC and this was reversed by TNT treatments, suggesting a link between the TNT-mediated antinociceptive effect and PFC VEGF expression.

Conclusion: Repeated oral administration of TNT reduces SNI-induced mechanical allodynia, and this effect appears to be associated with the regulation of prefrontal cortex PFC VEGF expression.