nnc-55-0396 has been researched along with Visceral-Pain* in 2 studies
2 other study(ies) available for nnc-55-0396 and Visceral-Pain
| Article | Year |
|---|---|
Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis.
Hydrogen sulfide (H(2)S), formed by multiple enzymes, including cystathionine-γ-lyase (CSE), targets Ca(v)3.2 T-type Ca(2+) channels (T channels) and transient receptor potential ankyrin-1 (TRPA1), facilitating somatic pain. Pancreatitis-related pain also appears to involve activation of T channels by H(2)S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca(v)3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T-channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H(2)S donor. In the mice with cerulein-induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55-0396 (NNC), a selective T-channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca(v)3.2 selectively among three T-channel isoforms; and knockdown of Ca(v)3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein-induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca(v)3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein-induced pancreatitis. The data indicate that TRPA1 and Ca(v)3.2 mediate the exogenous H(2)S-induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca(v)3.2 targeted by H(2)S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. Topics: Analysis of Variance; Animals; Benzimidazoles; Calcium Channel Blockers; Calcium Channels, T-Type; Ceruletide; Cyclopropanes; Disease Models, Animal; Hydrogen Sulfide; Hyperalgesia; Isothiocyanates; Male; Mice; Naphthalenes; Oligodeoxyribonucleotides, Antisense; Pancreatitis; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Transient Receptor Potential Channels; TRPA1 Cation Channel; Visceral Pain | 2015 |
Colonic hydrogen sulfide-induced visceral pain and referred hyperalgesia involve activation of both Ca(v)3.2 and TRPA1 channels in mice.
Luminal hydrogen sulfide (H(2)S), a gasotransmitter, causes colonic pain / referred hyperalgesia in mice, most probably via activation of T-type Ca(2+) channels. Here we analyzed the mechanisms for H(2)S-induced facilitation of colonic pain signals. Intracolonic administration of NaHS, an H(2)S donor, evoked visceral pain-like nociceptive behavior and referred hyperalgesia in mice, an effect abolished by NNC 55-0396, a selective T-type Ca(2+)-channel blocker, or by knockdown of Ca(v)3.2. AP18, a TRPA1 blocker, also prevented the NaHS-induced colonic pain and referred hyperalgesia. These findings demonstrate that H(2)S-induced colonic pain and referred hyperalgesia require activation of both Ca(v)3.2 and TRPA1 channels in mice. Topics: Animals; Benzimidazoles; Calcium Channels, T-Type; Cyclopropanes; Female; Hydrogen Sulfide; Hyperalgesia; Mice; Naphthalenes; Nociceptors; Sulfides; Transient Receptor Potential Channels; TRPA1 Cation Channel; Visceral Pain | 2012 |