Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

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Abstract

Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

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Most cited references 67

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Biological effects of resveratrol.

L Frémont (2000)

Resveratrol (3, 4', 5 trihydroxystilbene) is a naturally occuring phytoalexin produced by some spermatophytes, such as grapevines, in response to injury. Given that it is present in grape berry skins but not in flesh, white wine contains very small amounts of resveratrol, compared to red wine. The concentrations in the form of trans- and cis- isomers of aglycone and glucosides are subjected to numerous variables. In red wine, the concentrations of the trans-isomer, which is the major form, generally ranges between 0.1 and 15 mg/L. As phenolic compound, resveratrol contributes to the antioxidant potential of red wine and thereby may play a role in the prevention of human cardiovascular diseases. Resveratrol has been shown to modulate the metabolism of lipids, and to inhibit the oxidation of low-density lipoproteins and the aggregation of platelets. Moreover, as phytoestrogen, resveratrol may provide cardiovascular protection. This compound also possesses anti-inflammatory and anticancer properties. However, the bioavailability and metabolic pathways must be known before drawing any conclusions on the benefits of dietary resveratrol to health.

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A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.

A Akopian, L Sivilotti, J Wood (1996)

Dorsal root ganglion sensory neurons associated with C-fibres, many of which are activated by tissue-damage, express an unusual voltage-gated sodium channel that is resistant to tetrodotoxin. We report here that we have identified a 1,957 amino-acid sodium channel in these cells that shows 65% identity with the rat cardiac tetrodotoxin-insensitive sodium channel, and is not expressed in other peripheral and central neurons, glia or non-neuronal tissues. In situ hybridization shows that the channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia. The channel is resistant to tetrodotoxin when expressed in Xenopus oocytes. The electrophysiological and pharmacological properties of the expressed channel are similar to those described for the small-diameter sensory neuron tetrodotoxin-resistant sodium channels. As some noxious input into the spinal cord is resistant to tetrodotoxin, block of expression or function of such a C-fibre-restricted sodium channel may have a selective analgesic effect.

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Can we conquer pain?

Clifford Woolf, Joachim Scholz (2002)

Pain can be an adaptive sensation, an early warning to protect the body from tissue injury. By the introduction of hypersensitivity to normally innocuous stimuli, pain may also aid in repair after tissue damage. Pain can also be maladaptive, reflecting pathological function of the nervous system. Multiple molecular and cellular mechanisms operate alone and in combination within the peripheral and central nervous systems to produce the different forms of pain. Elucidation of these mechanisms is key to the development of treatments that specifically target underlying causes rather than just symptoms. This new approach promises to revolutionize pain diagnosis and management.

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Author and article information

Contributors

Paula Andrade: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 11 October 2016

Publication date Collection: October 2016

Volume: 17

Issue: 10

Electronic Location Identifier: 1702

Affiliations

[1 ]Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan; me1605@ 123456azabu-u.ac.jp (S.T.); che.4.mar29@ 123456gmail.com (K.S.); shimazu@ 123456azabu-u.ac.jp (Y.S.)

[2 ]FANCL Health Science Research Center, Research Institute, FANCL corporation, 12-13, Kamishinano, Totsuka-ku, Yokohama, Kanagawa 244-0806, Japan; yoshiko_0909@ 123456fancl.co.jp

Author notes

[* ]Correspondence: m-takeda@ 123456azabu-u.ac.jp ; Tel.: +81-42-769-1886; Fax: +81-42-769-2212

Article

Publisher ID: ijms-17-01702

DOI: 10.3390/ijms17101702

PMC ID: 5085734

PubMed ID: 27727178

SO-VID: f289cbe7-fc79-42c7-8d51-c8ceb099a207

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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

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Abstract

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Neuronal Signaling

Most cited references 67

Biological effects of resveratrol.

A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.

Can we conquer pain?

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