Characterization of Insulin Antinociception in Mice

Abstract

The present investigation is aimed at the characterization of insulin induced antinociceptive activity in experimental models. At the outset, the antinociceptive activity of insulin was established in 3 different assay procedures namely acetic acid induced abdominal constriction assay, hot plate and tail clip methods. In all the three assay procedures, insulin produced a significant antinociceptive response. The validity of the assay was established using a known potent analgesic morphine. Administration of exogenous insulin significantly reduced the number of acetic acid induced abdominal constrictions, increased the reaction time in hot plate and tail flick procedures thereby confirming that the insulin when administered exogenously elicited a significant antinociceptive response. The potency of this activity of insulin was found to be approximately 70% in all the assay procedures tested. Further, this activity of insulin was found to be dose related and time dependent. The activity was noticeable after 0.01 IU/kg (very low dose) and the maximal response was noticeable after 2 IU/kg. It was found to be maximum 30 min after insulin administration and minimum after 180 min. Insulin is a potent hypoglycemic hormone. It was the focus of the study whether this antinociceptive response was associated with the hypoglycemic effect of insulin. Insulin was able to elicit antinociceptive response in doses (0.01 and 0.1 IU/kg) at which no significant hypoglycemic response was induced. The present findings lead to the conclusion that insulin possesses an inherent dose and time related antinociceptive response independent of its hypoglycemic activity. Possibly, this response may be the factor responsible for the relief in pain in diabetic neuropathy patients receiving insulin. It is established that resistance develops to insulin induced hypoglycemia. Similarly, tolerance also develops to its antinociceptive response. This novel effect of insulin is to be exploited for proper clinical utility based on further warranted clinical trials.