Cannabinoid receptor agonists from Conus venoms alleviate pain-related behavior in rats

Jergová, Stanislava; Perez, Cecilia; Imperial, Julita S.; Gajavelli, Shyam; Jain, Aakangsha; Abin, Adam; Olivera, Baldomero M.; Sagen, Jacqueline

doi:10.1016/j.pbb.2021.173182

Cited by 4 publications

(4 citation statements)

References 86 publications

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“…The larger volume of cyclotides, approximately eight times that of endogenous 2-AG and other cannabinoids, may account for the moderate affinity and potency of vodo-C1 at CB 2 R. The bulkier size might impede deep penetration of the receptor binding-core ( 18 ) (∼415–447 Å³), ideally suited for binding of small molecule cannabinoid ligands ( 41 ). Peptide ligands of cannabinoid receptors like vodo-C1, including the recently discovered venom peptides that target CB 1 R ( 59 ) may preferably interact with the extracellular regions of the binding pocket. While molecular details of peptide-ligand interaction with the CB 2 R remain speculative, the identification of vodo-C1 as a plant-derived peptide CB 2 R agonist expands the list known phytocannabinoids.…”

Section: Discussionmentioning

confidence: 99%

Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor

Tomašević,

Emser,

Muratspahić

et al. 2024

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor

Tomašević,

Emser,

Muratspahić

et al. 2024

Journal of Biological Chemistry

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“…The interphase during the formalin test is characterized by the absence of algogenic compounds, and the mechanism underlying this phenomenon remains unclear (27). In the formalin test, the response behavior of lifting, flinching, and licking the injected paw is recorded and quantified (28,29). Prior studies have shown that an injection of formaldehyde solution in the hind paw, ranging from 19-616 mM, elicits an immediate first phase response characterized by pain-related licking behavior.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the parameters and biological mechanisms of CO2 laser therapy for acute pain relief

Wang,

Liu,

Wang

et al. 2023

Front. Neurol.

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Acute pain-related pathology is a significant challenge in clinical practice, and the limitations of traditional pain-relief drugs have made it necessary to explore alternative approaches. Photobiomodulation (PBM) therapy using CO2 laser has emerged as a promising option. In this study, we aimed to identify the optimal parameters of CO2 laser irradiation for acute pain relief through in vivo and in vitro experiments. First, we validated the laser intensity used in this study through bone marrow mesenchymal stem cells (BMSCs) experiments to ensure it will not adversely affect stem cell viability and morphology. Then we conducted a detailed evaluation of the duty cycle and frequency of CO2 laser by the hot plate and formalin test. Results showed a duty cycle of 3% and a frequency of 25 kHz produced the best outcomes. Additionally, we investigated the potential mechanisms underlying the effects of CO2 laser by immunohistochemical staining, and found evidence to suggest that the opioid receptor may be involved in its analgesic effect. In conclusion, this study provides insights into the optimal parameters and underlying mechanisms of CO2 laser therapy for effective pain relief, thereby paving the way for future clinical applications.

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“…Cultures were rinsed with Hyclone phosphate buffered solution (PBS; Sigma-Aldrich), fixed with 4% paraformaldehyde overnight and washed with Hyclone PBS. Fixed cells were immunostained overnight with Alexa 594 conjugated anti-hemagglutinin 1:500 (2μL/mL, Invitrogen, ThermoFisher, USA) to visualize the CB1 receptor [54,56,57]. Excess antibody was removed and cells were washed with PBS and counter-stained with 4', 6-diamidino-2-phenylindole (DAPI) to reveal the nuclei.…”

Section: Cb1 Redistribution Assaymentioning

confidence: 99%

Combined non-psychoactive Cannabis components cannabidiol and β-caryophyllene reduce chronic pain via CB1 interaction in a rat spinal cord injury model

et al. 2023

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The most frequently reported use of medical marijuana is for pain relief. However, its psychoactive component Δ9-tetrahydrocannabinol (THC) causes significant side effects. Cannabidiol (CBD) and β-caryophyllene (BCP), two other cannabis constituents, possess more benign side effect profiles and are also reported to reduce neuropathic and inflammatory pain. We evaluated the analgesic potential of CBD and BCP individually and in combination in a rat spinal cord injury (SCI) clip compression chronic pain model. Individually, both phytocannabinoids produced dose-dependent reduction in tactile and cold hypersensitivity in male and female rats with SCI. When co-administered at fixed ratios based on individual A50s, CBD and BCP produced enhanced dose-dependent reduction in allodynic responses with synergistic effects observed for cold hypersensitivity in both sexes and additive effects for tactile hypersensitivity in males. Antinociceptive effects of both individual and combined treatment were generally less robust in females than males. CBD:BCP co-administration also partially reduced morphine-seeking behavior in a conditioned place preference (CPP) test. Minimal cannabinoidergic side effects were observed with high doses of the combination. The antinociceptive effects of the CBD:BCP co-administration were not altered by either CB2 or μ-opioid receptor antagonist pretreatment but, were nearly completely blocked by CB1 antagonist AM251. Since neither CBD or BCP are thought to mediate antinociception via CB1 activity, these findings suggest a novel CB1 interactive mechanism between these two phytocannabinoids in the SCI pain state. Together, these findings suggest that CBD:BCP co-administration may provide a safe and effective treatment option for the management of chronic SCI pain.

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Cannabinoid receptor agonists from Conus venoms alleviate pain-related behavior in rats

Cited by 4 publications

References 86 publications

Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor

Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor

Unraveling the parameters and biological mechanisms of CO2 laser therapy for acute pain relief

Combined non-psychoactive Cannabis components cannabidiol and β-caryophyllene reduce chronic pain via CB1 interaction in a rat spinal cord injury model

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