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

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.