Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats

Barón-Flores, Verónica; Dı́az-Ruiz, Araceli; Navarrete, Francisco; Rı́os, Camilo; Burelo, Masha; Jardon-Guadarrama, Gustavo; Martínez-Cárdenas, María de los Ángeles; Mata-Bermúdez, Alfonso

doi:10.1016/j.neulet.2022.136855

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Cannabinoids have been shown to be effective in attenuation of pain-related behaviors in a wide variety of rodent inflammatory and peripheral neuropathy models, primarily via interaction with peripheral or spinal nociceptors [14,16,23,58,[69][70][71][72][73][74]. However, there have thus far been limited studies evaluating the effects of naturally-derived cannabis components in preclinical SCI pain models [75,76] and only a few investigating synthetic CB1/ 2 agonists for this indication in preclinical models, primarily from work on our laboratory [41,43,77]. Further, strong CB1 agonists can additionally mediate undesirable CNS effects with systemic administration.…”

Section: Plos Onementioning

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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Section: Plos Onementioning

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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“…In in vivo studies, the antinociceptive effect of cannabidiol (CBD) (from 2.5 to 20 mg/kg i.p.) as an acute treatment for neuropathic pain induced by spinal cord injury was investigated in female Wistar rats [142]. The results demonstrated a dose-dependent reduction in nociceptive behaviors, decreased lipid peroxidation levels, and increased GSH In comprehensive literature review, 30 randomized controlled trials and other studies were analyzed, revealing the promising effects of cannabis in refractory multiple sclerosis, cancer pain (especially in advanced stages), and chronic rheumatic pain [145].…”

Section: Cannabidiolmentioning

confidence: 99%

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

et al. 2023

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Neuropathic pain is a debilitating condition characterized by abnormal signaling within the nervous system, resulting in persistent and often intense sensations of pain. It can arise from various causes, including traumatic nerve injury, neuropathy, and certain diseases. We present an overview of current and emerging pharmacotherapies for neuropathic pain, focusing on novel drug targets and potential therapeutic agents. Current pharmacotherapies, including tricyclic antidepressants, gabapentinoids, and serotonin norepinephrine re-uptake inhibitors, are discussed, as are emerging treatments, such as ambroxol, cannabidiol, and N-acetyl-L-cysteine. Additionally, the article highlights the need for further research in this field to identify new targets and develop more effective and targeted therapies for neuropathic pain management.

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“…Many studies have reported that secondary injury is an important stage in the treatment of SCI. , Timely therapeutic intervention can inhibit the progression of secondary injury and have a significant impact on long-term neurological and functional recovery . The spinal cord microenvironment in the secondary injury phase produces large amounts of reactive oxygen species (ROS) (e.g., H 2 O 2 ). , The ROS cannot be metabolized in a timely manner and form accumulation, leading to local ischemia, hypoxia, and inflammatory cascade response . This further results in axonal degeneration, demyelination, and neuronal apoptosis. , Therefore, inhibiting the hyperaccumulation of ROS and alleviating the hypoxic environment are effective strategies in the treatment of SCI.…”

Section: Introductionmentioning

confidence: 99%

“…8 The spinal cord microenvironment in the secondary injury phase produces large amounts of reactive oxygen species (ROS) (e.g., H 2 O 2 ). 9,10 The ROS cannot be metabolized in a timely manner and form accumulation, leading to local ischemia, hypoxia, and inflammatory cascade response. 11 This further results in axonal degeneration, demyelination, and neuronal apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Membrane-Coated MnO₂ Nanoparticles Provide Neuroprotection by Reducing Oxidative Stress after Spinal Cord Injury

An,

Jiang,

et al. 2023

ACS Appl. Nano Mater.

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Secondary injury following spinal cord injury (SCI) results in a large production of reactive oxygen species (ROS) (e.g., H 2 O 2 ) in the spinal cord microenvironment, which then leads to an excessive burst of inflammation and ultimately neuronal death. In this study, we prepared manganese dioxide (MnO 2 ) nanoparticles coated by macrophage membranes, named M@MnO 2 , to cope with early ROS bursts in the SCI microenvironment. The biosafety and targeting ability of the MnO 2 nanoparticles were improved through the macrophage membranes. Successful preparation of M@MnO 2 was verified by transmission electron microscopy, Western blot, and dynamic light scattering. Small animal imaging showed that M@MnO 2 accumulated in large quantities at the site of SCI. In the early stages of SCI, M@MnO 2 effectively reduced the ROS content, as well as the hypoxia-inducible factor 1α (HIF-1α) content, malondialdehyde content, and superoxide anion content caused by ROS, further leading to a decrease in some of the proteins associated with inflammation at the site of SCI (CD11b, CD86, COX2, IL-1β, and iNOS), ultimately achieving neuroprotection and recovery of motor function.

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Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats

Cited by 8 publications

References 35 publications

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

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

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

Macrophage Membrane-Coated MnO₂ Nanoparticles Provide Neuroprotection by Reducing Oxidative Stress after Spinal Cord Injury

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Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats

Cited by 8 publications

References 35 publications

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

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

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain

Macrophage Membrane-Coated MnO2 Nanoparticles Provide Neuroprotection by Reducing Oxidative Stress after Spinal Cord Injury

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Macrophage Membrane-Coated MnO₂ Nanoparticles Provide Neuroprotection by Reducing Oxidative Stress after Spinal Cord Injury