Mechanical hyperalgesia in streptozotocin-diabetic rats.
Recent evidence strongly suggests that the hyperalgesia induced by agents acting directly on the primary afferent is mediated by stimulatory G-proteins and the cAMP second messenger system. In this study, we used the Randall-Selitto paw-pressure device to study hyperalgesia that develops in the streptozotocin-diabetic rat. Subcutaneous injection of streptozotocin in male Sprague-Dawley rats induced hyperglycemia and glucosuria detectable within 24 h of injection. A decrease in mechanical nociceptive threshold in the hindpaw was detected after one week. Intradermal injection of indomethacin, a cyclooxygenase inhibitor, had no significant effect on nociceptive threshold; and prostaglandin E2, which produces hyperalgesia by a direct action on the primary afferent, decreased nociceptive threshold similarly in streptozotocin-diabetic and control rats. Guanosine 5'-O-(2-thiodiphosphate), which blocks stimulatory G-proteins, attenuated the prostaglandin E2-hyperalgesia in both streptozotocin-diabetic and control rats, but had no effect on baseline nociceptive threshold in either group. Intradermal injection of either 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, or phosphodiesterase, which degrades cAMP, increased mechanical nociceptive threshold in streptozotocin-diabetic rats whilst not affecting mechanical nociceptive threshold in the control rats. Intradermal injection of 8-bromo cAMP, a membrane-permeable analog of cAMP, produced hyperalgesia of significantly greater magnitude in the streptozotocin-diabetic rats than the control rats. Intradermal injection of N6-cyclopentyl adenosine, an A1-type adenosine agonist, which can activate an inhibitory G-protein and decrease cAMP production, also increased nociceptive thresholds in streptozotocin-diabetic rats. This effect was blocked by pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
Ahlgren
S C
SC
Department of Anatomy, University of California, San Francisco.
Levine
J D
JD
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D015124:8-Bromo Cyclic Adenosine Monophosphate; C048599:N(6)-cyclopentyladenosine; D016048:Dideoxyadenosine; C023427:guanosine 5'-O-(2-thiodiphosphate); C021008:2',5'-dideoxyadenosine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D015232:Dinoprostone; D007213:Indomethacin