POSSIBLE MECHANISM OF HYPERGLYCEMIA INDUCED DECREASE IN ANTINOCICEPTIVE EFFECT OF ANALGESICS IN RATSAbstract
Diabetes induced neuropathic pain is recognized as one of the most difficult pain to treat and conventional analgesic are well known to be partially effective or ineffective. Non-steroidal anti-inflammatory drugs and opioids are effective antinociceptive drugs, however, their antinociceptive activity decreased in diabetic neuropathy. The study was designed to investigate the mechanism of diabetes induced decrease in the antinociceptive effect of analgesics in rats. Streptozotocin (STZ) (20 mg/kg, i. p. 4 days) was administered to induce experimental diabetes in the rats. One week after the administration of STZ, the tail-flick and paw withdrawal test was performed. Spleen homogenate supernatant (SHS) was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 µl, i. v.) for 28 days. Thermal hyperalgesia was noted in both diabetic and SHS (400 µl, i. v.) treated non-diabetic rats. Moreover, analgesic effect of morphine (8mg/kg, s.c.), lysine acetylsalicylic acid (400mg/kg i. v) and indomethacin (10 mg/kg, i. p.) was progressively decrease in diabetic and SHS of 28 day diabetic treated non diabetic rats. However, analgesic effect of morphine (8mg/kg s. c.), lysine acetylsalicylic acid (400mg/kg i.v) and indomethacin (10 mg/kg, i. p.) were improved in splenctomised diabetic rat. Administration of Cyclosporine (25 mg/kg, i.p), an IL-2 inhibitor, attenuated diabetes and SHS induced decrease in nociceptive threshold. It is concluded that spleen derived factor (s) and cytokines may be responsible for the observed decrease in antinociceptive effect of analgesics in diabetic rats.
Rajeev Taliyan *, Manjeet Singh # and Pyarelal Sharma
I. S. F. College of Pharmacy, Moga (Punjab), India
28 February, 2010
24 April 2010
26 April 2010
01 May, 2010