Muscarinic cholinergic system of the dorsal hippocampus involvement in the modulation of formalin-induced orofacial nociception and relevant memory impairment in rats

Behav Brain Res. 2025 Apr 27:484:115518. doi: 10.1016/j.bbr.2025.115518. Epub 2025 Feb 28.

Abstract

The hippocampus is well recognized for its significant contributions to learning, memory formation, and emotional regulation. In addition, it was approved by several studies that hippocampus plays a pivotal role in pain modulation; however, the exact mechanism has not yet been identified. In the current research, effects of microinjection of muscarinic M1 cholinergic agents into the CA1 region of the hippocampus in orofacial nociception evoked by formalin and corresponding memory impairment were investigated. Left and right sides of the hippocampus were implanted by guide cannulas. Orofacial nociception was elicited through subcutaneously injection of formalin (1.5 %) solution into the pad of vibrissa region. Evaluating memory was conducted with Morris water maze (MWM). Microinjections of McN-A-343 (a selective agonist of muscarinic M1 receptors) attenuated the both phases of orofacial nociceptive behavior, face rubbing. This effect of McN-A-343 was blocked by prior microinjection of pirenzepine (an antagonist of muscarinic receptors). On the other hand, McN-A-343 and pirenzepine increased and decreased traveled time as well as traveled distance in target zone of MWM, respectively. Additionally, McN-A-343 improved the memory deficits caused by orofacial nociception. Our results indicate that muscarinic acetylcholine receptors contribute significantly in the hippocampal modulation of orofacial nociception and related memory impairment.

Keywords: Cholinergic agents; Hippocampus; Memory impairment; Orofacial nociception; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / administration & dosage
  • Animals
  • CA1 Region, Hippocampal* / drug effects
  • CA1 Region, Hippocampal* / metabolism
  • CA1 Region, Hippocampal* / physiopathology
  • Disease Models, Animal
  • Facial Pain* / chemically induced
  • Facial Pain* / complications
  • Facial Pain* / metabolism
  • Facial Pain* / physiopathology
  • Formaldehyde / toxicity
  • Male
  • Memory Disorders* / diagnosis
  • Memory Disorders* / etiology
  • Memory Disorders* / metabolism
  • Memory Disorders* / physiopathology
  • Microinjections
  • Morris Water Maze Test
  • Muscarinic Agonists / administration & dosage
  • Muscarinic Antagonists / administration & dosage
  • Nociception / drug effects
  • Nociception / physiology
  • Nociceptive Pain* / chemically induced
  • Nociceptive Pain* / complications
  • Nociceptive Pain* / metabolism
  • Nociceptive Pain* / physiopathology
  • Pirenzepine / administration & dosage
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M1 / agonists
  • Receptor, Muscarinic M1 / antagonists & inhibitors
  • Receptor, Muscarinic M1 / metabolism
  • Stereotaxic Techniques

Substances

  • Formaldehyde
  • Receptor, Muscarinic M1
  • (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
  • Muscarinic Agonists
  • Pirenzepine
  • Muscarinic Antagonists