Dataset Information

(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5.

ABSTRACT: Recently, we found that the deletion of TRPC5 leads to increased inflammation and pain-related behaviour in two animal models of arthritis. (-)-Englerin A (EA), an extract from the East African plant Phyllanthus engleri has been identified as a TRPC4/5 agonist. Here, we studied whether or not EA has any anti-inflammatory and analgesic properties via TRPC4/5 in the carrageenan model of inflammation. We found that EA treatment in CD1 mice inhibited thermal hyperalgesia and mechanical allodynia in a dose-dependent manner. Furthermore, EA significantly reduced the volume of carrageenan-induced paw oedema and the mass of the treated paws. Additionally, in dorsal root ganglion (DRG) neurons cultured from WT 129S1/SvIm mice, EA induced a dose-dependent cobalt uptake that was surprisingly preserved in cultured DRG neurons from 129S1/SvIm TRPC5 KO mice. Likewise, EA-induced anti-inflammatory and analgesic effects were preserved in the carrageenan model in animals lacking TRPC5 expression or in mice treated with TRPC4/5 antagonist ML204.This study demonstrates that while EA activates a sub-population of DRG neurons, it induces a novel TRPC4/5-independent analgesic and anti-inflammatory effect in vivo. Future studies are needed to elucidate the molecular and cellular mechanisms underlying EA's anti-inflammatory and analgesic effects.

SUBMITTER: de Sousa Valente J

PROVIDER: S-EPMC8232259 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5.

de Sousa Valente João J Alawi Khadija M KM Bharde Sabah S Zarban Ali A AA Kodji Xenia X Thapa Dibesh D Argunhan Fulye F Barrett Brentton B Nagy Istvan I Brain Susan D SD

International journal of molecular sciences 20210615 12

Recently, we found that the deletion of TRPC5 leads to increased inflammation and pain-related behaviour in two animal models of arthritis. (-)-Englerin A (EA), an extract from the East African plant <i>Phyllanthus engleri</i> has been identified as a TRPC4/5 agonist. Here, we studied whether or not EA has any anti-inflammatory and analgesic properties via TRPC4/5 in the carrageenan model of inflammation. We found that EA treatment in CD1 mice inhibited thermal hyperalgesia and mechanical allody ...[more]

PMID: 34203675

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Project description:Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

Dataset Information

(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5.

Publications

(-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5.

Similar Datasets

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