Calcium channels blockers toxins attenuate abdominal hyperalgesia and inflammatory response associated with the cerulein-induced acute pancreatitis in rats
| Autor: | Marcelo Araújo Buzelin, Elizete Maria Rita Pereira, Vanice Paula Ricardo Carvalho, Duana Carvalho dos Santos, André Luiz Senna Guimarães, Danuza Montijo Diniz, Nancy Scardua Binda, Juliana Figueira da Silva, Márcia Helena Borges, Marcus Vinicius Gomez, Cláudio Antônio da Silva Júnior |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Pain Threshold Anti-Inflammatory Agents Spider Venoms Pharmacology omega-Conotoxins 03 medical and health sciences 0302 clinical medicine medicine Animals Calcium Signaling Rats Wistar Receptor Pancreas Analgesics Voltage-dependent calcium channel Behavior Animal business.industry Neuropeptides Chronic pain Visceral pain medicine.disease Calcium Channel Blockers Abdominal Pain Disease Models Animal 030104 developmental biology Nociception Pancreatitis Spinal Cord Hyperalgesia Exploratory Behavior Acute pancreatitis Calcium Channels medicine.symptom Inflammation Mediators business 030217 neurology & neurosurgery Ceruletide |
| Zdroj: | European journal of pharmacology. 891 |
| ISSN: | 1879-0712 |
| Popis: | Agents that modulate the activity of high-voltage gated calcium channels (HVCCs) exhibit experimentally and clinically significant effect by relieving visceral pain. Among these agents, the toxins Phα1β and ω-conotoxin MVIIA effectively reduce chronic pain in rodent models. The molecular mechanisms underlying the chronic pain associated with acute pancreatitis (AP) are poorly understood. Hypercalcemia is a risk factor; the role of cytosolic calcium is considered to be a modulator of pancreatitis. Blockade of Ca2+ signals may be useful as a prophylactic treatment of pancreatitis. We explored the pathophysiological roles of three peptide toxins: Phα1β and its recombinant form CTK 01512-2-blockers of TRPA1 receptor and HVCCs and ω-conotoxin MVIIA, a specific blocker of N-type calcium channels in cerulein-induced AP. Cerulein injection elicits AP in rats, evidenced by an increase in hyperalgesic pain, inflammatory infiltration, amylase and lipase secretion, and reactive oxygen species, TNF-α, and p65 NF-κB levels. These effects of cerulein-induced AP were abolished by Phα1β and its recombinant form CTK 01512-2, whereas ω-conotoxin MVIIA had no effect on the induced increase in pancreatic enzyme secretion. Our results demonstrate that Phα1β and CTK 01512-2 toxins-antagonists of HVCCs and TRPA1 receptor presented an effective response profile, in the control of nociception and inflammatory process in the AP model in rats, without causing changes in spontaneous locomotion of the rats. |
| Databáze: | OpenAIRE |
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