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Reduced neuropathic pain behavior in mice lacking the cyclic nucleotide-gated channel subunit CNGB1

: Kallenborn-Gerhardt, W.; Lu, R.; Petersen, J.J.; Metzner, K.; Kuth, M.S.; Heine, S.; Drees, O.; Paul, M.; Becirovic, E.; Kennel, L.; Flauaus, C.; Gross, T.; Wack, G.; Hohmann, S.W.; Turco, D. del; Biel, M.; Geisslinger, G.; Michalakis, S.; Schmidtko, A.

Naunyn-Schmiedebergs archives of pharmacology 392 (2019), Supplement 1, S.S16-S17
ISSN: 0028-1298
ISSN: 1432-1912
German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT Annual Meeting) <85, 2019, Stuttgart>
Association of the Clinical Pharmacology Germany (VKliPha Annual Meeting) <21, 2019, Stuttgart>
Fraunhofer IME ()

Question: Several cAMP and cGMP signaling pathways contribute to the generation of chronic pain conditions. However, the downstream targets of cAMP- and cGMP-dependent signaling in this context are not completely understood. One important target of cAMP and cGMP in the olfactory and visual system are cyclic nucleotide-gated (CNG) channels. Several lines of evidence indicate that these channels are also expressed in nociceptive tissues and are involved in pain processing. Here, we addressed the question if CNG channels contribute to the processing of neuropathic pain.
Methods: Quantitative real-time reverse transcription-polymerase chain reaction, in-situ hybridization, and immunohistochemically experiments were carried out to characterize the regulation and localization of CNG channel subunits in the mouse dorsal root ganglia (DRG). The spared nerve injury (SNI) and chronic constriction injury (CCI) model were performed to evaluate neuropathic pain. Electrophysiological recordings were used to investigate effects of a CNGB1 inhibitor on action potential firing. Intrathecal injections were performed to analyze cAMP- and cGMP-mediated pain signaling.
Results: CNGB1-containing CNG channels are expressed in DRGs and the spinal cord and are upregulated after peripheral nerve injury. CNGB1-deficient mice show reduced neuropathic pain behavior after peripheral nerve injury and reduced pain behavior after intrathecal cAMP delivery. Moreover, the neuropathic pain behavior and action potential firing of DRG neurons in wild-type mice was significantly reduced after treatment with a CNGB1 inhibitor.
Conclusion: These data suggest that CNGB1-positive CNG channels affect neuropathic pain processing after peripheral nerve injury by modulating neuronal activity in mice.