Efficacy of Tramadol in Thermoreversibles Gels in a Model of Postoperative Pain

Abstract

Tramadol (TR) is an opioid analgesic with short duration of action, still it may be consider valuable when compared to other opioids, as it produces mild adverse effects. Due to these properties, trmadol was incorporated in thermoreversible poloxamers and the effectiveness of these new drug delivery formulations was evaluated in a rat model of postoperative pain. The poloxamer (PL)‐tramadol systems were prepared by direct dispersion of the drug in solutions with PL 407 (20%) or the association of PL 407 (20%) and PL 188 (10%). Male Wistar rats were submitted to hindpaw incision and after 24 hours treated by subcutaneous route with one of the two formulations or plain TR 2% (10 μg.kg−1), saline or the poloxamers vehicles. Mechanical hypersensitivity was measured using von Frey filaments after 15, 30, 60, 90, 120,180, 240, 300 and 360 minutes from the injections. The protein levels of TNF‐α, IL‐1β, Substance P and CGRP were obtained through ELISA assays after 1, 3 and 6 hours after tramadol injections. All animals presented postincisional hypersensitivity showed by increased withdrawal response when compared to the preoperative period (p<0.05). Poloxamers formulations presented greater and longer analgesic effect than plain tramadol (p<0.05). Also, the new formulations were able to reduce the levels of TNF‐α after 6 hours (p<0.05). One hour far ahead of the formulations' injection CGRP levels with the PL 407 +PL 188 +TR 2% formulation was smaller than this vehicle without TR (p<0.05). The association of PL 407 and PL188 in an injectable formulation of tramadol promoted prolonged and effective postoperative pain relief in a rat model.Support or Funding InformationFAPESP (#2015/20744‐0)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.