Pain-Relieving Effectiveness of Co-Treatment with Local Tramadol and Systemic Minocycline in Carrageenan-Induced Inflammatory Pain Model

In this study, we tested our working hypothesis that inhibiting the activation of microglia by systemic minocycline treatments can decrease the dosage of local tramadol injection in inflammatory pain. This study was therefore aimed to evaluate the actions of intraplantarly injected tramadol, intraperitoneally injected minocycline, or their combined treatments on the inflammation-induced hypernociception (thermal hyperalgesia, mechanical allodynia), edema, and pro- and anti-inflammatory cytokine levels of paw and spinal cord tissues in a rat model of carrageenan-induced hindpaw inflammation. While local tramadol or systemic minocycline caused a significant anti-hypernociceptive effect their combined treatments significantly enhanced anti-hypernociceptive action compared to each agent applied alone. Also anti-edematous actions of combined treatment were higher than that of their individual administrations. In addition, combined treatment significantly decreased the level of the pro-inflammatory cytokines and caused significant increases in anti-inflammatory cytokine level of paw and spinal cord tissues. The present finding can suggest that combined treatments of local tramadol and systemic minocycline may decrease the dose requirements for anti-hypernociceptive actions of local tramadol and this combination therapy might be a beneficial option for the inflammatory pain relief.