Possible Role of Spleen Derived Factors, Vanilloid Receptors and Calcitonin Gene-related Peptide in Diabetes Induced Hyperalgesia in Mice

Abstract

The present study was designed to investigate a possible role of vanilloid receptors, CGRP and spleen in the induction of diabetes induced hyperalgesia in mice. Tail ‰ick latency, an index of hyperalgesia, was assessed using analgesiometer. Serum nitrite levels and an index of nitric oxide were analyzed using Griess reaction. Mice were rendered diabetic with streptozotocin (200 mg/kg -1 , i.p.) and kept for 30 days for development of diabetic pain. To explore the involvement of spleen in diabetic pain, spleen homogenate supernatant (SHS) was prepared from spleen of 30 th day diabetic mice and administered in normal mice for 14 days. Both in diabetic and SHS treated mice, signiˆcant degree of hyperalgesia was developed, suggesting the possible role of spleen derived factor in induction of diabetic pain. Moreover, the levels of nitric oxide were also elevated in 30 day diabetic mice and SHS treated mice. Administration of ruthenium red (1 mg/kg -1 , i.p.), vanilloid receptor antagonist, and sumatriptan (50 mg/kg -1 , i.p.), a CGRP release inhibitor, attenuated diabetes and SHS induced decrease in nociceptive threshold and increase in serum nitrite oxide levels. These results suggest that spleen derived factor induced activation of vanilloid receptors and CGRP release may be contributing in the development of hyperalgesia in diabetic mice.

Ameliorative Potential of Spironolactone in Diabetes Induced Hyperalgesia in Mice

“…It is reported from our 9,10,14) as well as from other laboratories 3) that a signiˆcant degree of hyperalgesia develops in mice after 4 weeks of STZ administration. Therefore in the present study mice were kept for 4 weeks after STZ administration to provide su‹cient time for hyperglycemia to aŠect pain perception.…”

“…These results are in consonance with our earlier report. 10) However, administration of SHS of spironolactone-treated diabetic mice failed to induce hyperalgesia and to increase serum nitrite levels. It is possible to suggest that spironolactone may have inhibited the production of spleen-derived factors involved in the induction of hyperalgesia in diabetic mice.…”

Animal models of neuropathic pain

“…STZ has also been employed to induce diabetic neuropathy in mice. It is reported from our [198][199][200][201] as well as from other laboratories [202] that significant degree of hyperalgesia develops in mice after 4 weeks of single dose STZ (200 mg/kg) administration. A new model has been developed to induce diabetes by an intravenous injection of STZ (50 mg/kg) through a tail vein.…”