Prostaglandin E2 and I2 facilitate noxious heat-induced spike discharge but not iCGRP release from rat cutaneous nociceptors
| Autor: | Peter W. Reeh, Gábor Petho, Alexandra Derow, Annette Kuhn, Iwona Izydorczyk |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Hot Temperature Calcitonin Gene-Related Peptide medicine.medical_treatment Action Potentials Neuropeptide Stimulation Calcitonin gene-related peptide Dinoprostone General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Neurons Efferent Internal medicine medicine Animals Thermosensing Neurons Afferent Rats Wistar General Pharmacology Toxicology and Pharmaceutics Prostaglandin E2 Skin Forskolin Nociceptors General Medicine Epoprostenol Rats Endocrinology chemistry Hyperalgesia Ionomycin Nociceptor lipids (amino acids peptides and proteins) Prostaglandin E medicine.drug |
| Zdroj: | Life Sciences. 81:1685-1693 |
| ISSN: | 0024-3205 |
| Popis: | The bradykinin-induced sensitization of cutaneous nociceptors to heat was previously shown to be abolished by cyclooxygenase blockade suggesting that endogenous prostaglandins exerted a heat-sensitizing action. The present study aimed at investigating the effects of exogenous prostaglandin E(2) (PGE(2)) and I(2) (PGI(2)) on noxious heat-evoked responses of rat cutaneous nociceptors. As neuropeptides including calcitonin gene-related peptide (CGRP) can be released from the peptidergic subset of heat-sensitive nociceptors, both the spike-generating (afferent) and CGRP-releasing (efferent) responses to heat stimulation were assessed by recording action potentials from single cutaneous C-fibers and measuring immunoreactive CGRP (iCGRP) release from isolated skin flaps, respectively. A combination of PGE(2) and PGI(2) (100 microM for both) unlike 10 microM PGE(2) or PGI(2) increased the number of spikes discharged during a noxious heat stimulus whereas the heat threshold remained unchanged. In contrast, 100 microM PGE(2) plus PGI(2) failed to increase the iCGRP release induced by noxious heat (47 degrees C) from the isolated rat skin. PGE(2) (100 microM), however, augmented the iCGRP-releasing effect of protons (pH 5.7). The adenylyl cyclase activator forskolin and the protein kinase C activator phorbol ester (PMA, 10 microM for both) facilitated heat-induced iCGRP release whereas increasing the intracellular Ca(2+) concentration by 10 microM ionomycin produced a desensitization of the response. In conclusion, PGE(2) plus PGI(2) can sensitize the afferent function of nociceptors in the rat skin, by increasing heat-induced spike discharge, but not the heat-induced efferent response i.e. iCGRP release. This discrepancy might reflect the differences between mechanisms of Na(+) channel-dependent spike generation and Ca(2+)-dependent neuropeptide release. |
| Databáze: | OpenAIRE |
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