Acetylcholine (ACh) causes a wide variety of anti-nociceptive effects. The dentate gyrus (DG) region of the hippocampal formation (HF) has been demonstrated to be involved in nociceptive perception. However, the mechanisms underlying this anti-nociceptive role have not yet been elucidated in the cholinergic pain-related neurons of DG. The electrical activities of pain-related neurons of DG were recorded by a glass microelectrocle. Two kinds of pain-related neurons were found: pain-excited neurons (PEN) and pain-inhibited neurons (PIN). The experimental protocol involved intra-DG administration of muscarinic cholinergic receptor (mAChR) agonist or antagonist. Intra-DG microinjection of 1 mu l of ACh (0.2 mu g/mu l) or 1 mu l of pilocarpine (0.4 mu g/mu l) decreased the discharge frequency of PEN and prolonged firing latency, but increased the discharge frequency Of PIN and shortened PIN inhibitory duration (ID). Intra-DG administration of 1 mu l of atropine (1.0 mu g/mu l) showed exactly the opposite effects. According to the above experimental results, we can presume that cholinergic pain-related neurons in DC are involved in the modulation of the nociceptive response by affecting the discharge of PEN and PIN. (C) 2009 Elsevier Inc. All rights reserved.