ABSTRACT
Peripheral neuropathy is a well-recognized complication of diabetes mellitus and achieving glycaemic control is presumed to be important in reducing its severity and progression. Meanwhile, the effect of hypoglycaemia on pain perception is less well studied. The current study compared the effects of four classes of oral hypoglycemics namely the sulfonylureas "glimepiride and glibenclamide", the biguanide "metformin", and the meglitinide analogue "repaglinide", besides the insulin sensitizer "rosiglitazone", in addition to insulin, sucrose and alloxan, on thermal pain using the hot-plate test in mice. Drugs were given 30 min prior to testing and blood glucose level determination. Alloxan was given 2hr before the assay. Glimepiride and glibenclamide [in two dose levels each] produced a reduction in nociceptive responses increasing hot-plate latency by 45.5-68.6% and by 18.1-12.8%, respectively, compared with pre-drug basal values. Hot-plate latency was increased by 66.2-32.8% following metformin. Rosiglitazone and repaglinide resulted in 26.7-39% and 50.1-43.1% increase in hot-plate latency, respectively. Insulin administered subcutaneously at 3 IU/kg decreased the nociceptive response by 19.5%, while a higher dose of 12 IU/kg caused 5.7% decrease in pain threshold. Hot-plate latency was also increased by oral [by 31.3-22.8%] or i.p. [by 50.1-37%] administration of 5% and 10% sucrose, respectively. Pain threshold decreased by 39.2% by alloxan [120 mg/kg, i.p.] and by 18.7% after both alloxan and glibenclamide [2.5 mg/kg, i.p.]. In case of glimepiride, insulin or alloxan treatment, correlation analysis showed relationship between the hot-plate latency and blood glucose level; R = 0.52, 0.51 and 0.72, respectively. It is concluded that within a certain range, reduction in blood glucose level impairs the perception of a thermal noxious stimulus