Activation of δ-opioid Receptors in Anterior Cingulate Cortex Alleviates Affective Pain in Rats.

The negative emotions caused by persistent pain, called affective pain, are known to seriously affect human physical and mental health. The anterior cingulate cortex (ACC), especially the rostral ACC (rACC) plays a key role in the development of this affective pain. N-methyl-d-aspartate (NMDA) receptors, which are widely distributed in the ACC, are involved in the regulation of emotional behavior. It is well known that activation of opioid receptors can relieve pain, but whether it can alleviate affective pain is not clear. In the present study, conditioned place avoidance (CPA) responses induced by complete Freund's adjuvant (CFA) were used to represent the affective pain of place aversion. The behavioral measurements were synchronously combined with multichannel electrophysiological recordings of the discharge frequency of rACC pyramidal neurons to explore whether affective pain could be alleviated by the synthetic opioid [D-Ala2, D-Leu5]-Enkefalin (DADLE), an agonist of δ-opioid receptors. To further investigate this treatment as a mechanism for the relief of affective pain in CFA-treated animals, we used whole-cell patch recordings in slice preparations of the rACC region to determine the dose-dependent effects of DADLE on NMDA receptor-mediated currents. Then, western blot was used to determine levels of phosphorylated NMDA receptor subunits GluN1, GluN2 and GluN3 as affected by the δ-opioid receptor activation. The results showed that activation of δ-opioid receptors down-regulates the phosphorylation of NMDA receptor subunits, thereby inhibiting NMDA currents, decreasing the discharge frequency of rACC pyramidal neurons, and reversing the CPA response. Thus, δ-opioid receptor activation in the rACC region can alleviate affective pain.

[Effects of sulfur dioxide on mRNA expression and activities of hepatic and pulmonary cytochrome P4502B1 and 2E1 in rats].

OBJECTIVE: To study the effects of sulfur dioxide (SO2) on activities and mRNA expression of hepatic and pulmonary cytochrome P4502B1 and 2E1 in rats. METHODS: Male Wistar rats were housed in exposure chambers and treated with 14, 28 and 56 mg/m3 SO2 for 6 h/d for 7 days, while control rats were exposed to filtered air in the same condition. The activities of CYP2E1 of rats were measured by spectrophotometry. Fluorescence spectrophotometry was used to study the activities of CYP2B1. The mRNAs of CYP2B1 and 2E1 were analyzed in livers and lungs by using a reverse transcription-polymerase chain reaction (RT-PCR) assay. RESULTS: In the liver, decreases of CYP2B1 activity and mRNA were observed at higher dose of SO2 (28 and 56 mg/m3). However, the CYP2E1-dependent p-nitrophenol hydroxylases (p-NP) and mRNA were unaltered by SO2 at all detected concentrations. For lungs, CYP2B1 activity was unaltered by SO2 at low concentrations, except for a significant decrease in the rats exposed to SO2 at 56mg/m3, however, SO2 at higher concentrations (28 and 56 mg/m3) significantly decreased CYP2B1 mRNA. Significant inhibition of p-NP was observed in lungs of rats exposed to SO2 at 28 and 56 mg/m3. SO2 at higher concentrations (28 and 56 mg/m3) decreased significantly pulmonary CYP2E1 mRNA relative to control animals. CONCLUSION: It was suggested that SO2 exposure could suppress the activities and mRNA expression of hepatic CYP2B1 and pulmonary CYP2B1 and 2E1 of rats.