Handbook of experimental pharmacology
-
Pain and itch are generally regarded antagonistic as painful stimuli such as scratching suppresses itch. Moreover, inhibition of pain processing by opioids generates itch further supporting their opposing role. Separate specific pathways for itch and pain processing have been uncovered, and several molecular markers have been established in mice that identify neurons involved in the processing of histaminergic and non-histaminergic itch on primary afferent and spinal level. ⋯ Rather than separating itch and pain, research concepts should therefore address the common mechanisms. Such an approach appears most appropriate for clinical conditions of neuropathic itch and pain and also chronic inflammatory conditions. While itch researchers can benefit from the large body of information of the pain field, pain researchers will find behavioral readouts of spontaneous itch much simpler than those for spontaneous pain in animals and the skin as source of the pruritic activity much more accessible even in patients.
-
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.