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Eur J Pharmacol ; 891: 173672, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33190801

ABSTRACT

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 Phα1ß 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: Phα1ß 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 Phα1ß 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 Phα1ß 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.


Subject(s)
Abdominal Pain/prevention & control , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels/drug effects , Hyperalgesia/prevention & control , Pain Threshold/drug effects , Pancreatitis/prevention & control , Abdominal Pain/etiology , Abdominal Pain/metabolism , Abdominal Pain/physiopathology , Animals , Behavior, Animal/drug effects , Calcium Channels/metabolism , Calcium Signaling/drug effects , Ceruletide , Disease Models, Animal , Exploratory Behavior/drug effects , Hyperalgesia/etiology , Hyperalgesia/metabolism , Hyperalgesia/physiopathology , Inflammation Mediators/metabolism , Male , Neuropeptides/pharmacology , Pancreas/drug effects , Pancreas/metabolism , Pancreatitis/chemically induced , Pancreatitis/metabolism , Pancreatitis/physiopathology , Rats, Wistar , Spider Venoms/pharmacology , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/physiopathology , omega-Conotoxins/pharmacology
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