Non-Intoxicating Cannabinoids in Visceral Pain.

Cannabis and cannabis products are becoming increasingly popular options for symptom management of inflammatory bowel diseases, particularly abdominal pain. While anecdotal and patient reports suggest efficacy of these compounds for these conditions, clinical research has shown mixed results. To date, clinical research has focused primarily on delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is a ligand of classical cannabinoid receptors (CBRs). CBD is one of a large group of nonintoxicating cannabinoids (niCBs) that mediate their effects on both CBRs and through non-CBR mechanisms of action. Because they are not psychotropic, there is increasing interest and availability of niCBs. The numerous niCBs show potential to rectify abnormal intestinal motility as well as have anti-inflammatory and analgesic effects. The effects of niCBs are frequently not mediated by CBRs, but rather through actions on other targets, including transient receptor potential channels and voltage-gated ion channels. Additionally, evidence suggests that niCBs can be combined to increase their potency through what is termed the entourage effect. This review examines the pre-clinical data available surrounding these niCBs in treatment of abdominal pain with a focus on non-CBR mechanisms.

On the nature of action-sentence compatibility effects.

Strong versions of the embodied account of language processing propose that comprehension depends on the mental simulation of sensorimotor experiences conveyed by linguistic meaning. Primary support in favor of this view is based on demonstrations of processing advantages for compatibility between an action implied by sentence content and concurrent sensorimotor processing. Although these effects have been reported across a variety of contexts, various attempts to reproduce these results, both through direct replication and conceptual extension, have not been successful. We present a series of experiments that examine the viability of previous methods used to obtain compatibility effects and the validity of the typical interpretation of such effects as evidence for mental simulation of described actions. Our findings add to the growing body of evidence that compatibility between sentence content and sensorimotor processing does not produce robust compatibility effects. Further, our findings suggest the data obtained from some studies that have been successful in generating compatibility effects can be accounted for without appealing to the notion that these effects are due to the simulation of actions implied by the meaning of a sentence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Induction of antiviral interferon-stimulated genes by neuronal STING promotes the resolution of pain in mice.

Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors. Neuronal activation of STING promotes signaling through TANK-binding kinase 1 (TBK1) and triggers an IFN-ß response that mediates pain resolution. Notably, we found that mice expressing a nociceptor-specific gain-of-function mutation in STING exhibited an IFN gene signature that reduced nociceptor excitability and inflammatory hyperalgesia through a KChIP1-Kv4.3 regulation. Our findings reveal a role of IFN-regulated genes and KChIP1 downstream of STING in the resolution of inflammatory pain.