Cannabinoid receptor 1 positive allosteric modulator (GAT229) attenuates cisplatin-induced neuropathic pain in mice

Bagher, Amina M.; Binmahfouz, Lenah S.; Shaik, Rasheed A.; Eid, Basma G.

doi:10.1016/j.jsps.2022.12.011

Cited by 7 publications

(3 citation statements)

References 64 publications

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“…In seeking more effective innovative therapies, one should take into account the endocannabinoid system, a key regulator of chronic pain, especially through modulation of its main receptors, CB1 and CB2 [ 2 , 3 ]. Even though CB1 stimulation induced analgesia in several painful states [ 4 , 5 , 6 , 7 ], CB1 agonists are not ideal pain-relieving agents for clinical use due to their serious side effects, such as addiction, excessive sedation, fatigue, and dizziness [ 8 , 9 ]. Thus, the alternative of using CB2 receptor modulators could be a therapeutic advantage, as they lack the negative neurological effects induced by CB1 receptor modulation.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…They further verified that newly synthesized GAT229, a pure CB1-positive allosteric modulator alleviated neuropathic pain and slowed the progression of CIPN. GAT229 also abridged proinflammatory cytokines in mice dorsal root ganglia neurons through the brain-derived neurotrophic factor and nerve growth factor levels in mice DRG neurons [ 47 ]. Thapa et al, determined that painful responses were observed following the capsaicin stimulation of injured corneas in mice.…”

Section: Discussionmentioning

confidence: 99%

Eicosapentaenoic Acid Modulates Transient Receptor Potential V1 Expression in Specific Brain Areas in a Mouse Fibromyalgia Pain Model

Liao,

Yen,

Hsiao

et al. 2024

IJMS

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Pain is an unpleasant sensory and emotional experience accompanied by tissue injury. Often, an individual’s experience can be influenced by different physiological, psychological, and social factors. Fibromyalgia, one of the most difficult-to-treat types of pain, is characterized by general muscle pain accompanied by obesity, fatigue, sleep, and memory and psychological concerns. Fibromyalgia increases nociceptive sensations via central sensitization in the brain and spinal cord level. We used intermittent cold stress to create a mouse fibromyalgia pain model via a von Frey test (day 0: 3.69 ± 0.14 g; day 5: 2.13 ± 0.12 g). Mechanical pain could be reversed by eicosapentaenoic acid (EPA) administration (day 0: 3.72 ± 0.14 g; day 5: 3.69 ± 0.13 g). A similar trend could also be observed for thermal hyperalgesia. The levels of elements in the transient receptor potential V1 (TRPV1) signaling pathway were increased in the ascending pain pathway, including the thalamus, medial prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and cerebellum. EPA intake significantly attenuated this overexpression. A novel chemogenetics method was used to inhibit SSC and ACC activities, which presented an analgesic effect through the TRPV1 downstream pathway. The present results provide insights into the role of the TRPV1 signaling pathway for fibromyalgia and its potential as a clinical target.

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“…Furthermore, a CB1 receptor-positive allosteric modulator (GAT229) was also tested in cisplatin-induced peripheral neuropathy. GAT229 mitigated and slowed the progression of cisplatin-induced mechanical allodynia and heat thermal hyperalgesia without eliciting the typical manifestations associated with CB1 receptor activation, such as psychoactive effects, tolerance, and dependence [65]. Similarly, CB2 receptor agonists, such as AM1710 and JWH-133, have also been shown to suppress mechanical and cold allodynia in the cisplatin-induced neuropathic pain model [63,66].…”

Section: Role Of G Protein-coupled Receptors In Cisplatin-induced Per...mentioning

confidence: 99%

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

Becker,

Atuati,

Oliveira

2024

Cancers

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Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

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Cannabinoid receptor 1 positive allosteric modulator (GAT229) attenuates cisplatin-induced neuropathic pain in mice

Cited by 7 publications

References 64 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

Eicosapentaenoic Acid Modulates Transient Receptor Potential V1 Expression in Specific Brain Areas in a Mouse Fibromyalgia Pain Model

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

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