Cannabidiol‐rich non‐psychotropic <i>Cannabis sativa</i> L. oils attenuate peripheral neuropathy symptoms by regulation of <scp>CB2</scp>‐mediated microglial neuroinflammation

Borgonetti, Vittoria; Anceschi, Lisa; Brighenti, Virginia; Corsi, Lorenzo; Governa, Paolo; Manetti, Fabrizio; Pellati, Federica; Galeotti, Nicoletta

doi:10.1002/ptr.7710

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…Microglial cells were seeded in 6-well plates (3 × 10 5 cells/well) until 70–80% confluence was achieved. Protein extraction from tissues and cells was performed as described [ 42 ]. Briefly, proteins from BV2 cells were extracted by radioimmunoprecipitation assay (RIPA) buffer (50 mM Tris-HCl pH 7.4, 150 mM NaCl 1% sodium deoxycholate, 1% Tryton X-100, 2 mM PMSF) (Sigma-Aldrich, Italy).…”

Section: Methodsmentioning

confidence: 99%

The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition

et al. 2023

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Neuropathic pain is a chronic disabling condition with a 7–10% of prevalence in the general population that is largely undertreated. Available analgesic therapies are poorly effective and are often accompanied by numerous side effects. Growing evidence indicates cannabinoids are a valuable treatment opportunity for neuropathic pain. The endocannabinoid system is an important regulator of pain perception through the CB1 receptors, but CB1 agonists, while largely effective, are not always satisfactory pain-relieving agents in clinics because of their serious adverse effects. Recently, several CB2 agonists have shown analgesic, anti-hyperalgesic, and anti-allodynic activity in the absence of CB1-induced psychostimulant effects, offering promise in neuropathic pain management. The aim of this study was to evaluate the anti-neuropathic activity of a novel selective CB2 agonist, COR167, in a preclinical model of peripheral neuropathy, the spared nerve injury (SNI). Oral COR167, in a dose-dependent manner, attenuated mechanical allodynia and thermal hyperalgesia after acute and repeated administration, showing the absence of tolerance induction. At anti-neuropathic doses, COR167 did not show any alteration in the locomotor behavior. SNI mice showed increased microglial levels of HDAC1 protein in the ipsilateral side of the spinal cord, along with NF-kB activation. COR167 treatment prevented the HDAC1 overexpression and the NF-kB activation and increased the levels of the anti-inflammatory cytokine IL-10 through a CB2-mediated mechanism. Oral administration of COR167 shows promising therapeutic potential in the management of neuropathic pain conditions.

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Section: Methodsmentioning

confidence: 99%

The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition

et al. 2023

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“…CB2 expression is upregulated in microglia stimulated with pro-inflammatory cytokines, indicating a significant role of CB2 in the regulation of neuroinflammatory states (129). In line with this, CBD has been shown to exert a CB2dependant anti-inflammatory effect on microglial inflammation (23,130).…”

Section: Discussionmentioning

confidence: 86%

Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity

et al. 2023

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IntroductionThe implications of maternal overnutrition on offspring metabolic and neuroimmune development are well-known. Increasing evidence now suggests that maternal obesity and poor dietary habits during pregnancy and lactation can increase the risk of central and peripheral metabolic dysregulation in the offspring, but the mechanisms are not sufficiently established. Furthermore, despite many studies addressing preventive measures targeted at the mother, very few propose practical approaches to treat the damages when they are already installed.MethodsHere we investigated the potential of cannabidiol (CBD) treatment to attenuate the effects of maternal obesity induced by a cafeteria diet on hypothalamic inflammation and the peripheral metabolic profile of the offspring in Wistar rats.ResultsWe have observed that maternal obesity induced a range of metabolic imbalances in the offspring in a sex-dependant manner, with higher deposition of visceral white adipose tissue, increased plasma fasting glucose and lipopolysaccharides (LPS) levels in both sexes, but the increase in serum cholesterol and triglycerides only occurred in females, while the increase in plasma insulin and the homeostatic model assessment index (HOMA-IR) was only observed in male offspring. We also found an overexpression of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα), interleukin (IL) 6, and interleukin (IL) 1β in the hypothalamus, a trademark of neuroinflammation. Interestingly, the expression of GFAP, a marker for astrogliosis, was reduced in the offspring of obese mothers, indicating an adaptive mechanism to in utero neuroinflammation. Treatment with 50 mg/kg CBD oil by oral gavage was able to reduce white adipose tissue and revert insulin resistance in males, reduce plasma triglycerides in females, and attenuate plasma LPS levels and overexpression of TNFα and IL6 in the hypothalamus of both sexes.DiscussionTogether, these results indicate an intricate interplay between peripheral and central counterparts in both the pathogenicity of maternal obesity and the therapeutic effects of CBD. In this context, the impairment of internal hypothalamic circuitry caused by neuroinflammation runs in tandem with the disruptions of important metabolic processes, which can be attenuated by CBD treatment in both ends.

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“…CB2 activation decreases HDAC1 and IKBα expression, as well as promoting the release of anti-inflammatory cytokine IL-10 in microglia. 573 The levels of proinflammatory factors are declined, such as IL-1β and TNF-α, accompanied by NLRP3 inflammasome deactivation. 574 , 575 CB2 effects are not limited to peripheral inflammation inhibition.…”

Section: Intervention Methods For Pain Reliefmentioning

confidence: 99%

Pathology of pain and its implications for therapeutic interventions

Cao,

Xu,

Shi

et al. 2024

Sig Transduct Target Ther

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Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.

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Cannabidiol‐rich non‐psychotropic Cannabis sativa L. oils attenuate peripheral neuropathy symptoms by regulation of CB2‐mediated microglial neuroinflammation

Cited by 7 publications

References 44 publications

The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition

The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition

Cannabidiol treatment improves metabolic profile and decreases hypothalamic inflammation caused by maternal obesity

Pathology of pain and its implications for therapeutic interventions

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