Effect of acetylcholine receptors on the pain-related electrical activities in the hippocampal CA۳ region of morphine-addicted rats

Objective(s):To determine the effect of acetylcholine (ACh), pilocarpine, and atropine on pain evoked responses of pain excited neurons (PEN) and pain inhibited neurons (PIN) in hippocampal CA۳ region of morphine addicted rats. Materials and Methods:Female Wistar rats, weighing between ۲۳۰-۲۶۰ g were used in this study. Morphine addicted rats were generated by subcutaneous injection of increasing concentrations of morphine hydrochloride for six days. Trains of electrical impulses applied to the sciatic nerve were used as noxious stimulation and the evoked electrical activities of PEN or PIN in hippocampal CA۳ area were recorded using extracellular electrophysiological recording techniques in hippocampal slices. The effect of acetylcholine receptor stimulation byACh, the muscarinic agonist pilocarpine, and the muscarinic antagonist atropine on the pain evoked responses of pain related electrical activities was analyzed in hippocampal CA۳ area of morphine addicted rats. Results:Intra-CA۳ microinjection of ACh (۲ μg/۱ μl) or pilocarpine (۲ μg/۱ μl) decreased the discharge frequency and prolonged the firing latency of PEN, but increased the discharge frequency and shortened the firing inhibitory duration (ID) of PIN. The intra-CA۳ administration of atropine (۰.۵ μg/۱ μl) produced opposite effect. The peak activity of cholinergic modulators was ۲ to ۴ min later in morphine addicted rats compared to peak activity previously observed in normal rats. Conclusion: ACh dependent modulation of noxious stimulation exists in hippocampal CA۳ area of morphine addicted rats. Morphine treatment may shift the sensitivity of pain related neurons towards a delayed response to muscarinergic neurotransmission in hippocampal CA۳ region.

Keywords:

Hippocampal CA۳ , Morphine addiction , Muscarinergic Acetylcholine receptors , Pain