Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis

Abstract The mechanisms underlying the transition from acute nociceptive pain to centrally maintained chronic pain are not clear. We have studied the contributions of the peripheral and central nervous systems during the development of osteoarthritis (OA) pain. Male Sprague-Dawley rats received unil...

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Autores principales: Adrian R. Haywood, Gareth J. Hathway, Victoria Chapman
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/36f66a4657fd4e7baa3ccf7573cded97
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spelling oai:doaj.org-article:36f66a4657fd4e7baa3ccf7573cded972021-12-02T11:41:04ZDifferential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis10.1038/s41598-018-25581-82045-2322https://doaj.org/article/36f66a4657fd4e7baa3ccf7573cded972018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25581-8https://doaj.org/toc/2045-2322Abstract The mechanisms underlying the transition from acute nociceptive pain to centrally maintained chronic pain are not clear. We have studied the contributions of the peripheral and central nervous systems during the development of osteoarthritis (OA) pain. Male Sprague-Dawley rats received unilateral intra-articular injections of monosodium iodoacetate (MIA 1 mg) or saline, and weight-bearing (WB) asymmetry and distal allodynia measured. Subgroups of rats received intra-articular injections of, QX-314 (membrane impermeable local anaesthetic) + capsaicin, QX-314, capsaicin or vehicle on days 7, 14 or 28 post-MIA and WB and PWT remeasured. On days 7&14 post-MIA, but not day 28, QX-314 + capsaicin signficantly attenuated changes in WB induced by MIA, illustrating a crucial role for TRPV1 expressing nociceptors in early OA pain. The role of top-down control of spinal excitability was investigated. The mu-opioid receptor agonist DAMGO was microinjected into the rostroventral medulla, to activate endogenous pain modulatory systems, in MIA and control rats and reflex excitability measured using electromyography. DAMGO (3 ng) had a significantly larger inhibitory effect in MIA treated rats than in controls. These data show distinct temporal contribtuions of TRPV1 expressing nociceptors and opioidergic pain control systems at later timepoints.Adrian R. HaywoodGareth J. HathwayVictoria ChapmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Adrian R. Haywood
Gareth J. Hathway
Victoria Chapman
Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
description Abstract The mechanisms underlying the transition from acute nociceptive pain to centrally maintained chronic pain are not clear. We have studied the contributions of the peripheral and central nervous systems during the development of osteoarthritis (OA) pain. Male Sprague-Dawley rats received unilateral intra-articular injections of monosodium iodoacetate (MIA 1 mg) or saline, and weight-bearing (WB) asymmetry and distal allodynia measured. Subgroups of rats received intra-articular injections of, QX-314 (membrane impermeable local anaesthetic) + capsaicin, QX-314, capsaicin or vehicle on days 7, 14 or 28 post-MIA and WB and PWT remeasured. On days 7&14 post-MIA, but not day 28, QX-314 + capsaicin signficantly attenuated changes in WB induced by MIA, illustrating a crucial role for TRPV1 expressing nociceptors in early OA pain. The role of top-down control of spinal excitability was investigated. The mu-opioid receptor agonist DAMGO was microinjected into the rostroventral medulla, to activate endogenous pain modulatory systems, in MIA and control rats and reflex excitability measured using electromyography. DAMGO (3 ng) had a significantly larger inhibitory effect in MIA treated rats than in controls. These data show distinct temporal contribtuions of TRPV1 expressing nociceptors and opioidergic pain control systems at later timepoints.
format article
author Adrian R. Haywood
Gareth J. Hathway
Victoria Chapman
author_facet Adrian R. Haywood
Gareth J. Hathway
Victoria Chapman
author_sort Adrian R. Haywood
title Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
title_short Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
title_full Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
title_fullStr Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
title_full_unstemmed Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
title_sort differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/36f66a4657fd4e7baa3ccf7573cded97
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AT garethjhathway differentialcontributionsofperipheralandcentralmechanismstopaininarodentmodelofosteoarthritis
AT victoriachapman differentialcontributionsofperipheralandcentralmechanismstopaininarodentmodelofosteoarthritis
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