The effect of acetylcholine on pain-related electric activities in the hippocampal CA3 of rats

Abstract

Acetylcholine (ACh) regulates pain perception in the central nervous system. However, the mechanism of action of ACh on pain-related neurons in the hippocampal CA3 is not clear. The present study aimed to determine the effect of ACh, muscarinic ACh receptors (mAChRs) agonist pilocarpine and mAChRs antagonist atropine on the pain-evoked responses of pain-excited neuron (PEN) and pain-inhibited neuron (PIN) in the hippocampal CA3 of normal rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The electric activities of PEN or PIN in the hippocampal CA3 were recorded by using a glass microelectrode. Our results showed that, in the hippocampal CA3, the intra-CA3 microinjection of ACh (2 μg/1 μl) or pilocarpine (2 μg/1 μl) decreased the discharge frequency and prolonged firing latency of PEN, and increased the discharge frequency and shortened firing inhibitory duration (ID) of PIN, i.e. exhibiting the analgesic effect of ACh or pilocarpine. The intra-CA3 administration of atropine (0.5 μg/1 μl) produced an opposite effect. On the basis of the above-mentioned findings, we can deduce that ACh and mAChRs in the hippocampal CA3 are involved in the modulation of nociceptive response by regulating the electric activities of PEN and PIN.

Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats

“…The electric activities of PENs and PINs returned to normal level at 8 and 10 min after the noxious stimuli, respectively. Xiao et al [7], Yang et al [8], Li et al [9], and Jiao et al [32] focused on electric activities of pain-related neurons in the hippocampus after noxious stimuli for many years. In the hippocampal CA1 and CA3 area and dentate gyrus, cholinergic neurons and muscarinic receptors have effects on the electric activities of PENs and PINs, so that they are involved in pain modulation [7–9, 32].…”

“…Neuropathic pain induced hippocampal interleukin-1 beta (IL-1 β ) mRNA levels upregulation, and the changes of IL-1 β mRNA expression correlated with the injured side of the hippocampus [6]. Xiao et al [7], Yang et al [8], and Li et al [9] reported in a series of studies that acetylcholine (ACh) influences the pain-induced discharge frequency and the electric activities of pain-related neurons in the hippocampus of rats.…”

Acetylcholine plays an antinociceptive role by modulating pain-induced discharges of pain-related neurons in the caudate putamen of rats

“…At 20 min after injection, the electrical activities of all recorded pain-related neurons in the CPu reverted to the pretreatment values. We suggested that the recording duration of a pain-related neuron was 30 min to observe completely and eliminate the influence from repeated administrations [11,13,15]. The mammalian mAChR family contains five G protein-coupled receptors designated M1-M5.…”

“…The PENs, termed 'on-cells' by some researchers, may facilitate nociceptive transmission, whereas the PINs, termed 'offcells', probably inhibit nociception [14]. According to the distinctive responses of these neurons to nociceptive stimulus, their electrophysiological characteristics have been considered as important indices for nociceptive research [11,15]. An intra-CPu injection of 2 mg/2 ml norepinephrine increased the thermal pain threshold (long tail-flick latency) in rats and administration of 1 mg/2 ml phentolamine decreased this threshold (short tail-flick latency), suggesting that the CPu is involved in the nociceptive modulation [16].…”

“…Although accumulating evidence indicates that cholinergic agonists might be potent analgesics and mAChRs could serve as efficacious pharmacological targets for the treatment of pain, most reports have focused on the effects of cholinergic agents and mAChRs on pain modulation at the level of the spinal cord. In our previous study, we showed the involvement of the CA1 and CA3 areas and dentate gyrus of the hippocampus in the modulation of nociception by the cholinergic system [11]. However, the effect of the cholinergic system on the pain-induced discharges of pain-related neurons in the CPu of normal rats remains to be elucidated.…”