Cannabinoids-induced peripheral analgesia depends on activation of BK channels

Li, Yongfeng; Zhang, Leili; Wu, Yuwei; Zheng, Qiaohua; Chen, Mengjiao; Qian, Zhaoqiang; Wei, Chunling; Han, Jing; Liu, Zhiqiang; Ren, Wei; Liu, Yihui

doi:10.1016/j.brainres.2019.01.007

Cited by 13 publications

(13 citation statements)

References 34 publications

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“…In the present study, the synthetic cannabinoid HU210 did not significantly alleviate mechanical allodynia in inflammatory pain, while only the maximal dose (1 mg/kg) produced significant antinociceptive effect in the neuropathic pain model. Our results do not agree with previous work showing the efficacy of HU210 anti-allodynic effects in both models of inflammatory and neuropathic pain at relatively lower doses [44,45]. We attribute this to the different methodologies and pain models used.…”

Section: Discussioncontrasting

confidence: 99%

Analgesic Effects and Impairment in Locomotor Activity Induced by Cannabinoid/Opioid Combinations in Rat Models of Chronic Pain

et al. 2020

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Both opioids and cannabinoids have well-known antinociceptive effects in different animal models of chronic pain. However, unwanted side effects limit their use. The aim of this study is to evaluate the antinociceptive effect of combining synthetic cannabinoids with subtherapeutic doses of opioids, and to evaluate the effects of these drugs/combinations on rat’s locomotor activity. Intra-plantar injection of Complete Freund’s Adjuvant (CFA) into the left hindpaw and intraperitoneal injection of streptozotocin (STZ) were used to induce inflammatory and diabetic neuropathic pain in adult male Sprague-Dawley rats, respectively. Von Frey filaments were used to assess the antinociceptive effects of opioids (morphine and tramadol) and the synthetic cannabinoids (HU210 and WIN55212) or their combinations on CFA and STZ-induced mechanical allodynia. Open field test was used to evaluate the effect of these drugs or their combinations on locomotion. HU210 and WIN55212 did not produce significant antinociceptive effect on inflammatory pain while only the maximal dose of HU210 (1 mg/kg) was effective in neuropathic pain. Only the maximal doses of morphine (3.2 mg/kg) and tramadol (10 mg/kg) had significant anti-allodynic effects in both models. Tramadol (1 mg/kg) enhanced the antinociceptive effects of WIN55212 but not HU210 in neuropathic pain with no effect on inflammatory pain. However, in open field test, the aforementioned combination did not change tramadol-induced depression of locomotion. Tramadol and WIN55212 combination produces antinociceptive effects in neuropathic but not inflammatory pain at low doses with no additional risk of locomotor impairment, which may be useful in clinical practice.

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Section: Discussioncontrasting

confidence: 99%

Analgesic Effects and Impairment in Locomotor Activity Induced by Cannabinoid/Opioid Combinations in Rat Models of Chronic Pain

et al. 2020

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“…In addition, BK channels are expressed in vascular smooth muscle cells where they contribute to the regulation of vascular contractile tone [ 21 , 33 ]. Moreover, BK channels may participate in the anticonvulsant and vasorelaxant effects of cannabinoids [ 34 ] and mediate cannabinoid-induced peripheral analgesia and firing-suppressing effects in primary sensory afferents after nerve injury [ 35 ]. Indeed, blocking BK channels reverses the firing-suppression effect of CB receptor agonists and the CB receptor agonist-induced peripheral analgesia [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Potassium channels as molecular targets of endocannabinoids

Lin

2021

Channels

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Endocannabinoids are a group of endogenous mediators derived from membrane lipids, which are implicated in a wide variety of physiological functions such as blood pressure regulation, immunity, pain, memory, reward, perception, reproduction, and sleep. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) represent two major endocannabinoids in the human body and they exert many of their cellular and organ system effects by activating the G i/o protein-coupled, cannabinoid type 1 (CB1) and type 2 (CB2) receptors. However, not all effects of cannabinoids are ascribable to their interaction with CB1 and CB2 receptors; indeed, macromolecules like other types of receptors, ion channels, transcription factors, enzymes, transporters, and cellular structure have been suggested to mediate the functional effects of cannabinoids. Among the proposed molecular targets of endocannabinoids, potassium channels constitute an intriguing group, because these channels not only are crucial in shaping action potentials and controlling the membrane potential and cell excitability, thereby regulating a wide array of physiological processes, but also serve as potential therapeutic targets for the treatment of cancer and metabolic, neurological and cardiovascular disorders. This review sought to survey evidence pertaining to the CB1 and CB2 receptorindependent actions of endocannabinoids on ion channels, with an emphasis on AEA and potassium channels. To better understand the functional roles as well as potential medicinal uses of cannabinoids in human health and disease, further mechanistic studies to delineate interactions between various types of cannabinoids and ion channels, including members in the potassium channel superfamily, are warranted.

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“…In the carrageenaninduced rat paw swelling experiment, Yin et al, (2003) found that the amount of PGE2 in the foot swelling site of mice in the brucine 30 mg/kg experimental group was significantly lower than that in the blank control group (P < 0.05). Using paw retraction threshold (PWT) and paw retraction latency (PWL) to measure pain behavior in rats showed that brucine regulated peripheral analgesia through potassium channel (Li and Ren, 2019).…”

Section: Anti-inflammatory and Analgesic Effectsmentioning

confidence: 99%

Brucine: A Review of Phytochemistry, Pharmacology, and Toxicology

Huang

et al. 2020

Front. Pharmacol.

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Brucine, a weak alkaline indole alkaloid, is one of the main bioactive and toxic constituents of Nux-vomica. Modern pharmacology studies and clinical practice demonstrate that brucine possesses wide pharmacological activities, such as anti-tumor, anti-inflammatory, analgesic, and the effects on cardiovascular system and nervous system, etc. However, its central nervous system toxicity severely limits its clinical application. Herein, the physicochemical properties, pharmacological activities, and toxicity of brucine were reviewed, and the novel strategies to address the toxicity issues were discussed, aiming to bring new insights into further research and application of this active component.

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Cannabinoids-induced peripheral analgesia depends on activation of BK channels

Cited by 13 publications

References 34 publications

Analgesic Effects and Impairment in Locomotor Activity Induced by Cannabinoid/Opioid Combinations in Rat Models of Chronic Pain

Analgesic Effects and Impairment in Locomotor Activity Induced by Cannabinoid/Opioid Combinations in Rat Models of Chronic Pain

Potassium channels as molecular targets of endocannabinoids

Brucine: A Review of Phytochemistry, Pharmacology, and Toxicology

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