Involvement of nucleus raphe magnus in neuronal excitability of long term paracetamol-treated rats

Abstract

This study examined an involvement of nucleus raphe magnus (NRM) on neuronal excitability at cortex and trigeminal nucleus caudalis (TNC) of chronic paracetamol-treated rats. Male Wistar rats were separated into two main groups. The rats in paracetamol-treated group were intraperitoneally injected with 200 mg/kg paracetamol while 0.9% NaCl was injected in control rats for 30 days. In the first experiment, cortical spreading depression (CSD) event was initiated and direct current (DC) shift was recorded for 2 hours. Thirty minutes after CSD induction, the rats were injected with glutamate, muscimol or saline at NRM and continued signal recording. In the second experiment, TNC neuronal excitability was recorded during intravenous nitroglycerin (NTG) infusion for 2 hours. One hour after NTG infusion, glutamate, muscimol or saline was injected at NRM. After completion of electrophysiological recording, brain and TNC were collected and prepared for Fos immunohistochemical staining. From the first experiment, chronic paracetamol treatment can increase the number of CSD waves and Fos expression in cortex and TNC compared with the control group. Muscimol microinjection at NRM in control group significantly increased the number of CSD waves and Fos expression compared with saline microinjection. Though, glutamate microinjection did not change the number of CSD waves and FOS expression. Moreover, muscimol or glutamate microinjection in paracetamol-treated group did not alter the number of CSD waves and FOS expression compared with saline microinjection. In the second experiment, TNC neuronal excitability and Fos expression were increased after chronic paracetamol treatment compared with control group. Furthermore, glutamate injection in control group can decrease TNC neuronal excitability, while muscimol injection increased TNC neural excitability compared with saline microinjection. However, the neuronal excitability in paracetamol-treated group did not differ after glutamate or muscimol microinjection compared with saline microinjection. From these results, NRM was shown to modulate the cortical and TNC neuronal excitability. Chronic analgesic treatment leads to an alteration of NRM function which affects the central modulating system. The derangement of NRM may contribute to the pathogenesis of medication overuse headache.