Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2015
ReviewH2S and Pain: A Novel Aspect for Processing of Somatic, Visceral and Neuropathic Pain Signals.
Hydrogen sulfide (H2S) formed by multiple enzymes including cystathionine-γ-lyase (CSE) targets Cav3.2 T-type Ca2+ channels (T-channels) and transient receptor potential ankyrin-1 (TRPA1). Intraplantar and intracolonic administration of H2S donors promotes somatic and visceral pain, respectively, via activation of Cav3.2 and TRPA1 in rats and/or mice. Injection of H2S donors into the plantar tissues, pancreatic duct, colonic lumen, or bladder causes T-channel-dependent excitation of nociceptors, determined as phosphorylation of ERK or expression of Fos in the spinal dorsal horn. ⋯ In rats with neuropathy induced by L5 spinal nerve cutting or by repeated administration of paclitaxel, an anticancer drug, the neuropathic hyperalgesia is reversed by inhibitors of CSE or T-channels and by silencing of Cav3.2. Upregulation of Cav3.2 protein in DRG is detectable in the former, but not in the latter, neuropathic pain models. Thus, H2S appears to function as a nociceptive messenger by facilitating functions of Cav3.2 and TRPA1, and the enhanced function of the CSE/H2S/Cav3.2 pathway is considered to be involved in the pancreatitis- and cystitis-related pain and in neuropathic pain.
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Recent studies have made significant progress in the knowledge of how itch sensation is processed, especially the molecular identity of neurons involved in itch signaling, both in the dorsal root ganglion and spinal cord. Despite these advances, the organization of these neurons in dorsal spinal cord circuits and how they interact with other somatosensory modalities, such as pain or temperature, remain relatively unexplored. ⋯ Here we describe the discovery of B5-I neurons, a population of inhibitory interneurons that function to inhibit itch, and review the evidence that these neurons mediate the inhibition of itch by counter stimuli. These studies are helping to solve the long-standing question of why itch makes us scratch.