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Calcium channels blockers toxins attenuate abdominal hyperalgesia and inflammatory response associated with the cerulein-induced acute pancreatitis in rats
- Source :
- European journal of pharmacology. 891
- Publication Year :
- 2020
-
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 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 891
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....acd0f25ac58b6ce59788dbc14ab4a3c6