Involvement of cannabinoid type 1 receptor in fasting-induced analgesia

Abstract

The endocannabinoid system (ECS) is known to modulate not only food intake but also pain, especially via the cannabinoid type 1 receptor (CB1R) expressed throughout the central nervous system and the peripheral tissues. Our previous study demonstrated that fasting produces an analgesic effect in adult male mice, which is reversed by intraperitoneal (i.p.) administration of CB1R antagonist (SR 141716). In the present study, we further examined the effect of CB1R expressed in the peripheral tissues. In the formalin-induced inflammatory pain model, i.p. administration of peripherally restricted CB1R antagonist (AM 6545) reversed fasting-induced analgesia. However, intraplantar administration of SR 141716 did not affect fasting-induced analgesia. Furthermore, mRNA expression of CB1R did not change in the formalin model by fasting in the dorsal root ganglia. The formalin-induced c-Fos expression at the spinal cord level was not affected by fasting, and in vivo recording from the superficial dorsal horn of the lumbar spinal cord revealed that fasting did not affect formalin-induced neural activity, which indicates minimal involvement of the spinal cord in fasting-induced analgesia. Finally, when we performed subdiaphragmatic vagotomy to block the hunger signal from the gastrointestinal (GI) system, AM 6545 did not affect fasting-induced analgesia, but SR 141716 still reversed fasting-induced analgesia. Taken together, our results suggest that both peripheral and central CB1Rs contribute to fasting-induced analgesic effects and the CB1Rs in the GI system which transmit fasting signals to the brain, rather than those in the peripheral sensory neurons, may contribute to fasting-induced analgesic effects.

A Critical Involvement of Glutamatergic Neurons in the Anterior Insular Cortex for Subdiaphragmatic Vagotomy-induced Analgesia

“…While the effect of SDV has been well studied with focus on visceral disease and is critically associated with visceral pain [6,9,12], recent studies have demonstrated that SDV can relieve somatic pain as well [8,13]. We also confirmed SDV-induced analgesia in formalin-induced acute inflammatory pain condition Effect of Subdiaphragmatic Vagotomy on Acute Inflammatory Pain [14]. Given SDV attenuates pain originated from extraterritorial area which is not innervated by vagus nerve, supraspinal mechanisms are highly likely to contribute to SDV-induced analgesia in somatic pain conditions.…”

“…Moreover, SDV reduces pro-inflammatory gene expression in brain regions such as the basolateral amygdala (BLA) and central amygdala (CeA) in LPS-induced inflammatory pain condition [15]. We also observed that SDV produces pain reduction only in the second phase, not the first phase, of formalin test under acute inflammatory pain condition [14], which is consistent with a previous report [13]. As the second phase of formalin test is known to be mediated by central mechanisms [16,17], brain mechanisms might be also involved in SDV-induced analgesia.…”

“…We first confirmed whether SDV indeed produces the analgesic effect on spontaneous nocifensive behaviors in the acute inflammatory pain condition. We used formalin model, which is widely used to study acute inflammatory pain in many animal models [14,26,30]. A formalin test was performed one week after SDV or sham surgery in the male adult mice (Fig.…”

A Closer Look at the Cellular and Molecular Components of the Deep/Muscular Fasciae

“…It is well known that the endocannabinoid system plays an important role in pain modulation. In fact, the activation of CB1R is able to suppress pain signaling at the supraspinal, spinal and peripheral levels [ 57 ]. The endocannabinoid system can also modulate fibrosis and inflammation: its activation, in fact, can suppress proinflammatory cytokines such as IL-1beta and TNF-alpha and increase anti-inflammatory cytokines, providing antifibrotic activity [ 58 ].…”

Gene Expression Level and Immunohistochemical Localization of Cannabinoid and Cannabinoid-Related Receptors in The Small Intestine of Holstein Bulls (Bos Taurus Taurus)

“…Cattle was provided with a diet adhering to the specifications outlined in the Polish Feeding Standard, formulated to fulfill the nutritional needs for total digestible nutrients and crude protein (Włodarczyk and Budvytis, 2011). Bulls were fasted for a period of 12 hours before slaughter, and according to available knowledge, short term fasting should not affect the tested receptors (Lee et al, 2020). The sample size was determined using general guidelines for morphological sciences (Henry et al, 2016).…”