Methyl cinnamate alleviated CCI-induced upregualtion of spinal AMPA receptors and pain hypersensitivity by targeting AMPK

Gui, Yulong; Chen, Liang; Duan, Shunyuan; Guan, Li; Tang, Jing; Li, Aiyuan

doi:10.1016/j.ejphar.2018.05.033

Cited by 12 publications

(11 citation statements)

References 24 publications

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“…Upregulated IL-1β p17 in inflamed skin tissues of CFA-induced inflammation is involved in pain hypersensitivity [24]. The upregulated phosphorylation of AMPK has an analgesic effect on neuropathic pain [25]. CFA caused significant increases in the levels of pro-IL-1β and IL-1β p17 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Alteration of proinflammatory cytokines in the tissues plays a crucial role in alleviating painful conditions [11, 28]. Activation of AMPK exerts analgesic effects through various pathways in many pain models, such as chronic constriction injury (CCI)-induced neuropathic pain [25], incision-evoked pain [29], and painful diabetic neuropathy [30]. In the present study, we found that AMPK activator AICAR exerted an analgesic effect and inhibited the proinflammatory cytokine IL-1β and IL-1β p17 in mice of CFA-induced inflammatory pain.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression

Xiang¹,

Lin²,

Hu³

et al. 2019

J Neuroinflammation

159

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BackgroundChronic pain is a major clinical problem with limited treatment options. Previous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) can attenuate neuropathic pain. Inflammation/immune response at the site of complete Freund’s adjuvant (CFA) injection is known to be a critical trigger of the pathological changes that produce inflammatory pain. However, whether activation of AMPK produces an analgesic effect through inhibiting the proinflammatory cytokines, including interleukin-1β (IL-1β), in inflammatory pain remains unknown.MethodsInflammatory pain was induced in mice injected with CFA. The effects of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside, an AMPK activator), Compound C (an AMPK inhibitor), and IL-1ra (an IL-1 receptor antagonist) were tested at day 4 after CFA injection. Inflammatory pain was assessed with von Frey filaments and hot plate. Immunoblotting, hematoxylin and eosin (H&E) staining, and immunofluorescence were used to assess inflammation-induced biochemical changes.ResultsThe AMPK activator AICAR produced an analgesic effect and inhibited the level of proinflammatory cytokine IL-1β in the inflamed skin in mice. Moreover, activation of AMPK suppressed CFA-induced NF-κB p65 translocation from the cytosol to the nucleus in activated macrophages (CD68+ and CX3CR1+) of inflamed skin tissues. Subcutaneous injection of IL-1ra attenuated CFA-induced inflammatory pain. The AMPK inhibitor Compound C and AMPKα shRNA reversed the analgesic effect of AICAR and the effects of AICAR on IL-1β and NF-κB activation in inflamed skin tissues.ConclusionsOur study provides new information that AMPK activation produces the analgesic effect by inhibiting NF-κB activation and reducing the expression of IL-1β in inflammatory pain.Electronic supplementary materialThe online version of this article (10.1186/s12974-019-1411-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression

Xiang¹,

Lin²,

Hu³

et al. 2019

J Neuroinflammation

159

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“…Concerning the methyl cinnamate, a study investigated the molecular mechanism of the inhibition of CCI-induced mechanical and thermal hypersensitivity involved with neuropathic pain. The authors identified that methyl cinnamate reduces pain hypersensitive behaviors and CCI-induced upregulation of spinal AMPA receptors through activation of AMP-activated protein kinase [ 92 ].…”

Section: Bioactive Compounds From Eos Of Spice Plantsmentioning

confidence: 99%

Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications

et al. 2020

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Spice plants have a great influence on world history. For centuries, different civilizations have used them to condiment the foods of kings and nobles and applied them as embalming preservatives, perfumes, cosmetics, and medicines in different regions of the world. In general, these plants have formed the basis of traditional medicine and some of their derived substances have been utilized to treat different human diseases. Essential oils (EOs) obtained from these plants have been also used as therapeutic agents and have shown supportive uses in remedial practices. The discovery and development of bioactive compounds from these natural products, based on their traditional uses, play an important role in developing the scientific evidence of their potential pharmaceutical, cosmetic, and food applications. In the present review, using recent studies, we exhibit a general overview of the main aspects related to the importance of spice plants widely used in traditional medicine: Cinnamomum zeylanicum (true cinnamon), Mentha piperita (peppermint), Ocimum basilicum (basil), Origanum vulgare (oregano), Piper nigrum (black pepper), Rosmarinus officinalis (rosemary), and Thymus vulgaris (thyme); and we discuss new findings of the bioactive compounds obtained from their EOs, their potential applications, as well as their molecular mechanisms of action, focusing on their antioxidant activity. We also exhibit the main in vitro methods applied to determine the antioxidant activities of these natural products.

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“…Activating AMPK in dorsal root ganglion (DRG) neurons inhibits the activity of TRPA1 (Transient receptor potential ankyrin 1) and participates in analgesia of AICAR in diabetic neuropathic pain [30]. Activation of AMPK inhibits AMPA receptors in the spinal cord and produces an analgesic effect in the neuropathic pain model [31]. In our study, EA signi cantly activated the AMPK and relieved in ammatory pain, which was reversed by the AMPK inhibitor Compound C. The key role of AMPK in analgesia effect of EA is consistent with previous studies [8,32].…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Attenuates Inflammatory Pain by Activating AMPK/autophagy and Inhibiting iNOS and IL-1β in Inflamed Tissues

Xiang¹,

Cai²,

Hu³

et al. 2021

Preprint

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BackgroundElectroacupuncture (EA) produces analgesic effects on inflammatory pain partially via activating adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in the spinal cord. However, it is unclear whether EA activates AMPK in peripheral tissues in inflammatory pain. This study was aimed at determining whether EA promotes autophagy by activating AMPK to inhibit the expression of inflammatory mediators IL-1β and iNOS in inflamed skin tissues. MethodsIn CFA-induced inflammatory pain in mice, mechanical allodynia and thermal hyperalgesia were tested 2 hours after EA treatment. The AMPK antagonist Compound C was injected intraperitoneally 30 minutes before EA treatment. The analgesic effects of AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) were determined and its effects on autophagy, IL-1β and iNOS expression were detected. Also, the effects of the autophagy inhibitor 3-methyladenine (3-MA) on EA analgesia and iNOS/IL-1β expression in inflamed skin tissues were examined. The phosphorylation of AMPK (Thr172) and total AMPK proteins, LC3BII/I, autophagy substrate protein p62, IL-1β and iNOS were detected using Western blotting. Co-labeling of macrophages (CD68) with IL-1β and iNOS was detected using immunofluorescence. In addition, after NR8383 macrophages were treated with CFA, the effects of AICAR and Compound C on autophagy were determined using stubRFP-sensGFP-LC3 Lentivirus..ResultsEA reduced CFA-induced inflammatory pain, activated AMPK and autophagy, and inhibited iNOS and IL-1β expression in inflamed skin tissues. AICAR also attenuated CFA-induced hyperalgesia, promoted autophagy and inhibited iNOS and IL-1β expression in vivo and in vitro. In addition, the AMPK inhibitor Compound C reversed the effect of EA on autophagy. Pretreatment with 3-MA, an inhibitor of autophagy, inhibited the effect of EA on inflammatory pain and expression of iNOS and IL-1β in inflamed skin tissues. ConclusionsEA treatment alleviated inflammatory pain by activation of AMPK, enhancing autophagy, and inhibiting iNOS and IL-1β expression in the inflamed skin tissues.

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Methyl cinnamate alleviated CCI-induced upregualtion of spinal AMPA receptors and pain hypersensitivity by targeting AMPK

Cited by 12 publications

References 24 publications

AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression

AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression

Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications

Electroacupuncture Attenuates Inflammatory Pain by Activating AMPK/autophagy and Inhibiting iNOS and IL-1β in Inflamed Tissues

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