Abstract
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)
Keywords
StreptozotocinHyperalgesiaEndocrinologyInternal medicineNociceptionAdenosineMedicineChemistryPharmacologyDiabetes mellitusReceptor
MeSH Terms
8-Bromo Cyclic Adenosine MonophosphateAdenosineAdenylate Cyclase ToxinAnimalsDiabetes MellitusExperimentalDideoxyadenosineDinoprostoneGTP-Binding ProteinsGuanosine DiphosphateHyperalgesiaIndomethacinMaleMechanoreceptorsPainPertussis ToxinRatsRatsSprague-DawleySensory ThresholdsThionucleotidesVirulence FactorsBordetella
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Publication Info
- Year
- 1993
- Type
- article
- Volume
- 52
- Issue
- 4
- Pages
- 1049-1055
- Citations
- 125
- Access
- Closed
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Cite This
Sara Ahlgren,
Jon D. Levine
(1993).
Mechanical hyperalgesia in streptozotocin-diabetic rats.
Neuroscience
, 52
(4)
, 1049-1055.
https://doi.org/10.1016/0306-4522(93)90551-p
Identifiers
- DOI
- 10.1016/0306-4522(93)90551-p
- PMID
- 8450973