The H2S-producing enzyme CSE is dispensable for the processing of inflammatory and neuropathic pain.
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.
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
Katharina M J
KMJ
Syhr
Pharmazentrum Frankfurt/ZAFES, Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main, Germany.
Meike
M
Boosen
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
Stephan W
SW
Hohmann
Pharmazentrum Frankfurt/ZAFES, Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main, Germany.
Sebastian
S
Longen
Pharmazentrum Frankfurt/ZAFES, Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main, Germany.
Yvette
Y
Köhler
Pharmazentrum Frankfurt/ZAFES, Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main, Germany.
Josef
J
Pfeilschifter
Pharmazentrum Frankfurt/ZAFES, Institute of Pharmacology and Toxicology, Goethe University, Frankfurt am Main, Germany.
Karl-Friedrich
KF
Beck
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology - Project Group Translational Medicine and Pharmacology (IME-TMP), 60590 Frankfurt am Main, Germany.
Gerd
G
Geisslinger
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany.
Achim
A
Schmidtko
Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany. Electronic address: kallenborn@med.uni-frankfurt.de.
Wiebke
W
Kallenborn-Gerhardt
D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000633:toxicity; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology; D010147:Pain Measurement; D013116:Spinal Cord / Q000378:metabolism; D015854:Up-Regulation; D015054:Zymosan / Q000494:pharmacology
D005557:Formaldehyde; D015054:Zymosan; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
CSE; CTH; Chronic pain; Dorsal root ganglia; Hydrogen sulfide; Knockout mice