Hyaluronic acid induces activation of the κ-opioid receptor.

Barbara Zavan,Letizia Ferroni,Paola Brun,Paolo Pinton,Carlotta Giorgi,Girolamo Calò,Giovanni Abatangelo,Roberta Cortivo,Theodore John Price

doi:10.1371/journal.pone.0055510

Barbara Zavan, Letizia Ferroni + Show 7 more

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https://doi.org/10.1371/journal.pone.0055510

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Journal: PloS one	Publication Date: Jan 28, 2013
Citations: 23	License type: CC BY 4.0

Affiliation: University of Padua, University of Ferrara

Abstract

IntroductionNociceptive pain is one of the most common types of pain that originates from an injury involving nociceptors. Approximately 60% of the knee joint innervations are classified as nociceptive. The specific biological mechanism underlying the regulation of nociceptors is relevant for the treatment of symptoms affecting the knee joint. Intra-articular administration of exogenous hyaluronic acid (HA) in patients with osteoarthritis (OA) appears to be particularly effective in reducing pain and improving patient function.MethodsWe performed an in vitro study conducted in CHO cells that expressed a panel of opioid receptors and in primary rat dorsal root ganglion (DRG) neurons to determine if HA induces the activation of opioid peptide receptors (OPr) using both aequorin and the fluorescent dye Fura-2/AM.ResultsSelective agonists and antagonists for each OPr expressed on CHO cells were used to test the efficacy of our in vitro model followed by stimulation with HA. The results showed that HA induces stimulatory effects on the κ receptor (KOP). These effects of HA were also confirmed in rat DRG neurons, which express endogenously the OPr.ConclusionsHA activates the KOP receptor in a concentration dependent manner, with a pEC50 value of 7.57.

Highlights

Nociceptive pain is one of the most common types of pain that originates from an injury involving nociceptors
We performed an in vitro study conducted in CHO cells that expressed a panel of opioid receptors and in primary rat dorsal root ganglion (DRG) neurons to determine if hyaluronic acid (HA) induces the activation of opioid peptide receptors (OPr) using both aequorin and the fluorescent dye Fura-2/AM
Selective agonists and antagonists for each OPr expressed on CHO cells were used to test the efficacy of our in vitro model followed by stimulation with HA

Summary

Introduction

Nociceptive pain is one of the most common types of pain that originates from an injury involving nociceptors. Pain experts have divided the physical causes of pain into two types: neuropathic and nociceptive pain. Whereas neuropathic pain refers to the dysfunction of either the peripheral (peripheral neuropathy) or central (central neuropathy) nervous systems, nociceptive pain (the more common of the two) refers to the discomfort that results when a stimulus causes tissue damage to the muscles, bones, skin or internal organs [1]. An endless variety of stimuli can trigger nociceptive pain by activating nociceptors found primarily in the skin, joints (somatic sources) or the walls of organs (visceral sources). Though nociceptors are scarce in organs deep within the body, they are highly concentrated on the skin and joints [2]

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