Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray

Abstract

Western blot and GTPγS analyses reveal inflammatory pain–induced adaptations in the midbrain periaqueductal gray, which is critically involved in descending pain modulation. Pain upregulates the expression of the CB1 receptor and increases G-protein coupling in the periaqueductal gray.

Impact of Δ9-Tetrahydrocannabinol and oxycodone co-administration on measures of antinociception, dependence, circadian activity, and reward in mice

“…There is considerable interest in combination therapies of cannabinoids and opioids for analgesia. CB1 and µ-opioid receptors are co-expressed in areas throughout the pain neuraxis where they are poised interact in the context of analgesia(Wilson-Poe et al, 2021; Yu et al, 2022) and analgesic tolerance(Wilson-Poe et al, 2012; Wilson-Poe et al, 2013). Indeed, a wealth of preclinical evidence generally suggests co-administration of CB1 and µ-agonists result in enhanced antinociception, and synergy across different pain models(Welch and Stevens, 1992; Cichewicz et al, 1999; Cichewicz and McCarthy, 2003; Cichewicz et al, 2005; Wilkerson et al, 2016; Wilkerson et al, 2017; Maguire and France, 2018; Slivicki et al, 2018; Slivicki et al, 2020; Nielsen et al, 2022; Toniolo et al, 2022; Yu et al, 2022).…”

Persistent inflammation promotes endocannabinoid release and presynaptic cannabinoid 1 receptor desensitization

“…eCB levels in the PAG are increased almost immediately after acute inflammation induced by formalin injection into the hindpaw (Walker et al 1999) as well as after 7 days of chronic constriction injury, a model of neuropathic pain (Petrosino et al 2007). The observed CB1R desensitization in our study is likely a result of increased CB1R-induced G protein signaling within the vlPAG early in inflammation (Wilson-Poe et al 2021).…”

“…eCB levels in the PAG are increased almost immediately after acute inflammation induced by formalin injection into the hindpaw(Walker et al 1999) as well as after 7 days of chronic constriction injury, a model of neuropathic pain(Petrosino et al 2007). The observed CB1R desensitization in our study is likely a result of increased CB1R-induced G protein signaling within the vlPAG early in inflammation(Wilson-Poe et al 2021).We observed prolonged DSI after persistent inflammation, which is consistent with the time course in other studies pharmacologically or genetically inhibiting MAGL(Chen et al 2016, Pan et al 2009, Schlosburg et al 2010, Straiker & Mackie 2005. We show that the prolonged inhibition of GABAergic IPSCs following DSI in slices from CFA-treated rats is blocked by inhibiting DAGLa, the enzyme responsible for 2-AG synthesis, implicating 2-AG in the adaptations induced by CFA in the vlPAG.…”

Novel Approach to the Treatment of Neuropathic Pain Using a Combination with Palmitoylethanolamide and Equisetum arvense L. in an In Vitro Study

“…Furthermore, several studies affirmed that CB receptors on GABAergic neurons might also be needed for modulation of the nervous recovery mechanism located on Schwann cells, which detect nerve injury and provide the first response, playing a critical role in the development and maintenance of neuropathic pain [ 41 ]. According to the literature [ 42 , 43 , 44 ], endogenous cannabinoid ligands, such as PEA [ 45 ], and CB1 receptors are widely present in the nociceptive and descending inhibitory pathways. The CB1 receptor is expressed in both nerve endings of GABAergic and glutamatergic neurons, which provides histological evidence that the activation of the CB1 receptor may regulate GABAergic and glutamatergic neurotransmission [ 43 ].…”