An Investigation into the Role of Insulin in Pain Threshold

Abstract

The present study investigated the relation between endogenous insulin level and pain threshold and its interaction with opioid system and diurnal rhythm in animal model using different nociceptive tests and pentazocine as a model drug. We observed significant relation between endogenous insulin level and pain threshold independent of the glycemic status in acetic acid, formalin and tail flick models except in the hot plate model where such a relation seems dependent on the glycemic status. Insulin appears interacting with opioid receptor (kappa receptor) based on the preliminary study by protein-protein docking method. Endogenous insulin positively correlate with pain threshold which was found to be influenced by diurnal rhythm. Endogenous insulin level showed peak in the dark cycle and trough in the light cycle in all the pain models investigated. The study reports for the first time on the involvement of endogenous insulin in pain threshold against different nociceptive tests in animal models. The above findings clearly delineate that there seems to be no direct relation between blood glucose levels and antinociception, however, a possible involvement of endogenous insulin in pain threshold through opioid pathway by binding with kappa receptor which is independent of the glycemic status. The association between endogenous insulin and pain threshold seems dependent on the type of nociceptive stimuli and the endogenous insulin level and pain intensities seems influenced by diurnal rhythm. The present study clearly reveals the significant role of endogenous insulin in the modulation of pain utilizing opioid pathway. Our preliminary study on the interaction between endogenous insulin and opioid receptor show possible binding of insulin on kappa receptor. Future study is recommended to explore the mechanisms of insulin mediated antinociception through opioid pathway at molecular level. newline