Gözen Öksüz1, Tufan Mert2, Selma Yaman2, Mahmut Arslan1, Metin Kılınç31Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Anesteziyoloji
BACKGROUND AND AIM: The side effects observed and challenges posed by the use of opioids for treatment has encouraged scientists to seek new analgesics. Isovaline (2-amino-2-methylbutanoic acid) is a new and promising analgesic with an antinociceptive effect and, unlike µ-opioid agonists, interacts with aminobutyric acid (GABA) receptors without causing sedation or respiratory depression. The coadministration of isovaline with an opioid may therefore provide a stronger analgesic effect. In this study, we investigated if the combination of isovaline and tramadol could reduce the development of thermal hyperalgesia and mechanical allodynia in a carrageenan-induced hind paw inflammatory pain model in rats.
METHODS: In this study, isovaline and the combination of isovaline and tramadol were subcutaneously administered to rats with carrageenan-induced inflammation of the hind paws. Sensory abnormalities, such as hyperalgesia in response to thermal stimuli and allodynia in response to mechanic stimuli, were assessed by using a thermal plantar test and a dynamic plantar aesthesiometer, respectively.
RESULTS: When administered individually, isovaline and tramadol significantly elevated the latency and threshold (P<0.005). The latency is an indication of the anti-hyperalgesic action and the threshold is an indication of the anti-allodynic action of isovaline and tramadol administration. When isovaline was used in combination with tramadol, the latency and threshold were significantly higher than those after application of the treatments individually (P<0.005). The administration of isovaline or tramadol significantly decreased the carrageenan-injected paw mass compared with saline-injected paw mass (P<0.005) This indicated that the anti-edematous action of the combination of isovaline and tramadol was greater than that of their individual administration (P<0.005).
CONCLUSIONS: The results obtained in this study demonstrated that the subcutaneous administration of isovaline had analgesic efficacy and was effective in combination with tramadol, which is a weak opioid with few side effects when used for the treatment of inflammatory pain.