Publications by authors named "Stephan W Hohmann"

4 Publications

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Neuropathic and cAMP-induced pain behavior is ameliorated in mice lacking CNGB1.

Neuropharmacology 2020 07 6;171:108087. Epub 2020 Apr 6.

Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438, Frankfurt am Main, Germany.

Cyclic nucleotide-gated (CNG) channels, which are directly activated by cAMP and cGMP, have long been known to play a key role in retinal and olfactory signal transduction. Emerging evidence indicates that CNG channels are also involved in signaling pathways important for pain processing. Here, we found that the expression of the channel subunits CNGA2, CNGA3, CNGA4 and CNGB1 in dorsal root ganglia, and of CNGA2 in the spinal cord, is transiently altered after peripheral nerve injury in mice. Specifically, we show using in situ hybridization and quantitative real-time RT-PCR that CNG channels containing the CNGB1b subunit are localized to populations of sensory neurons and predominantly excitatory interneurons in the spinal dorsal horn. In CNGB1 knockout (CNGB1) mice, neuropathic pain behavior is considerably attenuated whereas inflammatory pain behavior is normal. Finally, we provide evidence to support CNGB1 as a downstream mediator of cAMP signaling in pain pathways. Altogether, our data suggest that CNGB1-positive CNG channels specifically contribute to neuropathic pain processing after peripheral nerve injury.
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http://dx.doi.org/10.1016/j.neuropharm.2020.108087DOI Listing
July 2020

The G2A receptor (GPR132) contributes to oxaliplatin-induced mechanical pain hypersensitivity.

Sci Rep 2017 03 27;7(1):446. Epub 2017 Mar 27.

Institute of Clinical Pharmacology, pharmazentrum frankfurt/ZAFES, University Hospital, Goethe-University, D-60590, Frankfurt am Main, Germany.

Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there is no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes CIPN in up to 80% of treated patients. Here, we report the involvement of the G-protein coupled receptor G2A (GPR132) in oxaliplatin-induced neuropathic pain in mice. We found that mice deficient in the G2A-receptor show decreased mechanical hypersensitivity after oxaliplatin treatment. Lipid ligands of G2A were found in increased concentrations in the sciatic nerve and dorsal root ganglia of oxaliplatin treated mice. Calcium imaging and patch-clamp experiments show that G2A activation sensitizes the ligand-gated ion channel TRPV1 in sensory neurons via activation of PKC. Based on these findings, we conclude that targeting G2A may be a promising approach to reduce oxaliplatin-induced TRPV1-sensitization and the hyperexcitability of sensory neurons and thereby to reduce pain in patients treated with this chemotherapeutic agent.
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http://dx.doi.org/10.1038/s41598-017-00591-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428564PMC
March 2017

The H2S-producing enzyme CSE is dispensable for the processing of inflammatory and neuropathic pain.

Brain Res 2015 Oct 10;1624:380-389. Epub 2015 Aug 10.

Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany. Electronic address:

Accumulating lines of evidence indicate that hydrogen sulfide (H2S) contributes to the processing of chronic pain. However, the sources of H2S production in the nociceptive system are poorly understood. Here we investigated the expression of the H2S releasing enzyme cystathionine γ-lyase (CSE) in the nociceptive system and characterized its role in chronic pain signaling using CSE deficient mice. We show that paw inflammation and peripheral nerve injury led to upregulation of CSE expression in dorsal root ganglia. However, conditional knockout mice lacking CSE in sensory neurons as well as global CSE knockout mice demonstrated normal pain behaviors in inflammatory and neuropathic pain models as compared to WT littermates. Thus, our results suggest that CSE is not critically involved in chronic pain signaling in mice and that sources different from CSE mediate the pain relevant effects of H2S.
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http://dx.doi.org/10.1016/j.brainres.2015.07.058DOI Listing
October 2015

Nox2-dependent signaling between macrophages and sensory neurons contributes to neuropathic pain hypersensitivity.

Pain 2014 Oct 17;155(10):2161-70. Epub 2014 Aug 17.

Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany. Electronic address:

Emerging lines of evidence indicate that production of reactive oxygen species (ROS) at distinct sites of the nociceptive system contributes to the processing of neuropathic pain. However, the mechanisms underlying ROS production during neuropathic pain processing are not fully understood. We here detected the ROS-generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages of dorsal root ganglia (DRG) in mice. In response to peripheral nerve injury, Nox2-positive macrophages were recruited to DRG, and ROS production was increased in a Nox2-dependent manner. Nox2-deficient mice displayed reduced neuropathic pain behavior after peripheral nerve injury, whereas their immediate responses to noxious stimuli were normal. Moreover, injury-induced upregulation of tumor necrosis factor α was absent, and activating transcription factor 3 induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated macrophage-neuron signaling. These data suggest that Nox2-dependent ROS production in macrophages recruited to DRG contributes to neuropathic pain hypersensitivity, underlining the observation that Nox-derived ROS exert specific functions during the processing of pain.
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http://dx.doi.org/10.1016/j.pain.2014.08.013DOI Listing
October 2014