Microglial Cannabinoid CB₂ Receptors in Pain Modulation

Pain, especially chronic pain, can strongly affect patients’ quality of life. Cannabinoids ponhave been reported to produce potent analgesic effects in different preclinical pain models, where they primarily function as agonists of Gi/o protein-coupled cannabinoid CB1 and CB2 receptors. The CB1 receptors are abundantly expressed in both the peripheral and central nervous systems. The central activation of CB1 receptors is strongly associated with psychotropic adverse effects, thus largely limiting its therapeutic potential. However, the CB2 receptors are promising targets for pain treatment without psychotropic adverse effects, as they are primarily expressed in immune cells. Additionally, as the resident immune cells in the central nervous system, microglia are increasingly recognized as critical players in chronic pain. Accumulating evidence has demonstrated that the expression of CB2 receptors is significantly increased in activated microglia in the spinal cord, which exerts protective consequences within the surrounding neural circuitry by regulating the activity and function of microglia. In this review, we focused on recent advances in understanding the role of microglial CB2 receptors in spinal nociceptive circuitry, highlighting the mechanism of CB2 receptors in modulating microglia function and its implications for CB2 receptor- selective agonist-mediated analgesia

An experimental study of liquid unloading in the curve section of horizontal gas wells

Liquid unloading is a very common and important issue in horizontal gas wells, and the presence of curve sections increases the complexity of the phenomenon and its study. Liquid loading in a gas well will sharply reduce production, therefore, the liquid-unloading onset of different curved pipes is essential to gas production. In this work, liquid-unloading onset experiments were conducted in curved pipes with different curvatures. Then, the critical gas velocity VsgCR can be determined according to the measured pressure gradients, liquid holdup, and liquid film reversal. This work analyzes the factors which will lead to the liquid unloading and explores the trend of the pipe curvature’s influence on the liquid unloading under laboratory conditions. The experimental results show that the critical gas velocity rises with the increase of pipe curvature, the increase is mainly due to the centrifugal force. The present work also compares the predicted results of the OLGA model and Beggs–Brill model with experimental data. The comparison results indicate that both models fit relatively well to the experimental data at the low superficial gas velocity, and both models have poor performance at high superficial gas velocity. The OLGA model fits the experimental data better than the Beggs–Brill model at high superficial gas velocity. The error analysis shows that most of the predicted data is not in good agreement with experimental data. Some errors between experimental data and calculation results are out of the range of 50%