Differential modulation of nociceptive responses to mu and kappa opioid receptor directed drugs by blood glucose in experimentally induced diabetes rats.

ABSTRACT

The study has evaluated the effect of diabetes associated hyperglycaemia on nociception and antinociception induced by morphine, buprenorphine and pentazocine in female albino rats. Rats were allocated into 3 groups of 20 each--group I consisted of control having normal blood glucose levels (BGLs), group II consisted of streptozotocin-induced diabetics (STZ-D) having hyperglycaemia and group III consisted of diabetic rats controlled with insulin treatment. Immediately before and 15, 30 min, 1, 2 and 3 hr after injection with test drugs, rats were subjected to a thermal noxious stimulus using tail withdrawal from hot water and tail-flick latencies (TFL) so generated were recorded. Similarly, before and 30, 45 min and 1 hr after injection with drugs rats were subjected to abdominal writhing with hypertonic saline and number of writhes were counted per 90 sec. In STZ-D animals (BGLs 317.95 +/- 3.8 mg/dl) a decreased TFL with an increase in the number of writhes compared to control and diabetes controlled with insulin treatment was observed. Percent maximum possible effect of morphine (5 mg/kg, s.c.) and buprenorphine (2 mg/kg, s.c.) was significantly lower when compared to control as well as STZ-D controlled with insulin treatment groups. Similarly percent protection from writhing of morphine (0.05 mg/kg, s.c.) and buprenorphine (0.01 mg/kg, s.c.) was significantly less in comparison to control and STZ-D controlled with insulin treatment group. However, percent maximum possible effect of pentazocine (20 mg/kg, s.c.) and percent protection from writhing of pentazocine (1 mg/kg, s.c.) was significantly high in STZ-D rats when compared to control and STZ-D rats controlled with insulin treatment groups. The results suggest that both mu and kappa--opioid receptors may be modulated by blood glucose levels possibly involving cellular energetics mediated change in potassium (KATP) channels in females rats, albeit differentially.