Role of Gangliosides in Peripheral Pain Mechanisms.

Péter Sántha,Gyöngyi Kis,Ildikó Dobos,Gábor Jancsó

doi:10.3390/ijms21031005

Péter Sántha, Gyöngyi Kis + Show 2 more

Open Access

https://doi.org/10.3390/ijms21031005

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Abstract

Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.

Highlights

Gangliosides are abundantly occurring sialylated glycosphingolipid s serving diverse functions in the nervous system
Inferred from the morphological observations, these findings indicated a putative role of GM1 ganglioside in the function of nociceptive primary sensory neurons possibly through interaction with membrane lipid microdomains/lipid rafts [104,107,108]
Investigations into the mechanisms of somatosensory functions, in particular transmission of nociceptive impulses have revealed that glycosphingolipids, including gangliosides may interfere with the function of primary sensory neurons through diverse interactions with membrane receptors/ion channels, lipid rafts, membrane, and intracellular signaling pathways, cellular calcium homeostasis, and immune mechanisms

Summary

Introduction

Gangliosides are abundantly occurring sialylated glycosphingolipid s serving diverse functions in the nervous system. These glycosphingolipids are primarily membrane-localized and through their oligosaccharide portion constitute specific recognition sites interacting with a variety of extracellular agents [1]. Gangliosides are integral components of membrane lipid microdomains (rafts) and may interact with membrane-bound functional proteins influencing their activation. Association of membrane receptor molecules with lipid microdomains has been shown to participate in the activation of a variety of ion channels or neurotransmitter receptors, including transient receptor potential (TRP) channels [2,3,4]. Gangliosides are important regulators/modulators of neural processes encompassing neural development and regeneration, intercellular communication, neurotrophic action, neurotransmission and other receptor-mediated functions [6,7,8,9,10]. The present review attempts to summarize available evidence supporting the role of gangliosides in conveying sensory, in particular nociceptive information from the periphery towards the central nervous system by primary sensory neurons under physiological and pathological conditions

Distribution of Gangliosides in Sensory Ganglia and Spinal Cord

Human Diseases Affecting Glycosphingolipid Metabolism and Pain

Ganglioside Species Involved in Pain Mechanisms

Interaction of TRP Receptors with Membrane Lipid Rafts

Findings

Conclusion and Perspectives