Schmidtko, Achim and Gao, Wei and Koenig, Peter and Heine, Sandra and Motterlini, Roberto and Ruth, Peter and Schlossmann, Jens and Koesling, Doris and Niederberger, Ellen and Tegeder, Irmgard and Friebe, Andreas and Geisslinger, Gerd (2008) cGMP produced by NO-sensitive guanylyl cyclase essentially contributes to inflammatory and neuropathic pain by using targets different from cGMP-dependent protein kinase I. JOURNAL OF NEUROSCIENCE, 28 (34). pp. 8568-8576. ISSN 0270-6474,
Full text not available from this repository. (Request a copy)Abstract
Alarge body of evidence indicates that the release of nitric oxide ( NO) is crucial for the central sensitization of pain pathways during both inflammatory and neuropathic pain. Here, we investigated the distribution of NO-sensitive guanylyl cyclase (NO-GC) in the spinal cord and in dorsal root ganglia, and we characterized the nociceptive behavior of mice deficient in NO-GC (GC-KO mice). Weshow that NO-GC is distinctly expressed in neurons of the mouse dorsal horn, whereas its distribution in dorsal root ganglia is restricted to non-neuronal cells. GC-KO mice exhibited a considerably reduced nociceptive behavior in models of inflammatory or neuropathic pain, but their responses to acute pain were not impaired. Moreover, GC-KO mice failed to develop pain sensitization induced by intrathecal administration of drugs releasing NO or carbon monoxide. Surprisingly, during spinal nociceptive processing, cGMP produced by NO-GC may activate signaling pathways different from cGMP-dependent protein kinase I (cGKI), whereas cGKI can be activated by natriuretic peptide receptor-B dependent cGMP production. Together, our results provide evidence that NO-GC is crucially involved in the central sensitization of pain pathways during inflammatory and neuropathic pain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; SUBSTANCE-P RECEPTOR; DORSAL-ROOT GANGLIA; FORMALIN-INDUCED HYPERALGESIA; PERIPHERAL-NERVE INJURY; SPINAL-CORD; CENTRAL SENSITIZATION; THERMAL HYPERALGESIA; NOCICEPTIVE NEURONS; DEFICIENT MICE; nitric oxide; natriuretic peptide; spinal cord; DRG; knock-out mice; pain behavior |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 09:17 |
| Last Modified: | 26 Oct 2020 09:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30466 |
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