Possible role of spleen-derived factors, vanilloid receptors and calcitonin gene-related peptide in diabetes induced hyperalgesia in mice.
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 flick 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 30th day diabetic mice and administered in normal mice for 14 days. Both in diabetic and SHS treated mice, significant 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.
Khan
Nadeem
N
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Punjab, India.
Singh
Nirmal
N
Jaggi
Amteshwar Singh
AS
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000502:physiology*; D013311:Streptozocin; D018170:Sumatriptan / Q000494:pharmacology / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
D050916:TRPV Cation Channels; D012430:Ruthenium Red; D009569:Nitric Oxide; D013311:Streptozocin; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide