Endogenous cholinergic system involved in peripheral analgesic control in mice is activated by TNF-α, CXCL-1 and IL-1 β

• Published in: Pharmacology
• Main Authors: Gonzaga, Amanda Cristina Reis, Quintão, Jayane Laís Dias, Galdino, Giovane, Romero, Thiago Roberto Lima, Silva, Grazielle Caroline da, Lemos, Virgínia Soares, Campolina-Silva, Gabriel Henrique, Oliveira, Cleida Aparecida de, Mahecha, Germán Arturo Bohórquez, Duarte, Igor Dimitri Gama
• Format: Journal Article
• Language: English
• Published: Switzerland 20.04.2024
• ISSN: 1423-0313
• DOI: 10.1159/000538995

Tissue injury results in the release of inflammatory mediators, including a cascade of algogenic substances, which contribute to the development of hyperalgesia. During this process, endogenous analgesic substances are peripherally released to counterbalance hyperalgesia. The present study aimed to investigate whether inflammatory mediators TNF-α, IL-1β, CXCL1, norepinephrine (NE) and prostaglandin E2 (PGE2) may be involved in the deflagration of peripheral endogenous modulation of inflammatory pain by activation of the cholinergic system. Male Swiss mice were subjected to paw withdrawal test. All the substances were injected via the intraplantar route. The main findings of this study were as follows: (1) carrageenan (Cg), TNF-α, CXCL-1, IL1-β, NE, and PGE2 induced hyperalgesia; (2) the acetylcholinesterase enzyme inhibitor, neostigmine, reversed the hyperalgesia observed after Cg, TNF-α, CXCL-1, and IL1-β injection; (3) The non-selective muscarinic receptor antagonist, atropine, and the selective muscarinic type 1 receptor (m1AChr) antagonist, telenzepine, potentiated the hyperalgesia induced by Cg and CXCL-1; (4) mecamylamine, a non-selective nicotinic receptor antagonist, potentiated the hyperalgesia induced by Cg, TNF-α, CXCL-1, and IL1-β; (5) Cg, CXCL-1, and PGE2 increased the expression of the m1AChr and nicotinic receptor subunit α4protein. These results suggest that the cholinergic system may modulate the inflammatory pain induced by Cg, PGE2, TNF-α, CXCL-1, and IL1-β.