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

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 in...

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Main Authors: Haywood, Adrian R., Hathway, Gareth J., Chapman, Victoria
Format: Article
Published: Nature Publishing Group 2018
Online Access:https://eprints.nottingham.ac.uk/51373/
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author Haywood, Adrian R.
Hathway, Gareth J.
Chapman, Victoria
author_facet Haywood, Adrian R.
Hathway, Gareth J.
Chapman, Victoria
author_sort Haywood, Adrian R.
building Nottingham Research Data Repository
collection Online Access
description 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 1mg) 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 signfcantly 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 refex excitability measured using electromyography. DAMGO (3ng) had a signifcantly 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.
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spelling nottingham-513732020-05-04T19:35:42Z https://eprints.nottingham.ac.uk/51373/ Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis Haywood, Adrian R. Hathway, Gareth J. Chapman, Victoria 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 1mg) 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 signfcantly 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 refex excitability measured using electromyography. DAMGO (3ng) had a signifcantly 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. Nature Publishing Group 2018-05-08 Article PeerReviewed Haywood, Adrian R., Hathway, Gareth J. and Chapman, Victoria (2018) Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis. Scientific Reports, 8 . 7122/1-7122/12. ISSN 2045-2322 https://www.nature.com/articles/s41598-018-25581-8 doi:10.1038/s41598-018-25581-8 doi:10.1038/s41598-018-25581-8
spellingShingle Haywood, Adrian R.
Hathway, Gareth J.
Chapman, Victoria
Differential contributions of peripheral and central mechanisms to pain in a rodent model of osteoarthritis
title 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_short 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
url https://eprints.nottingham.ac.uk/51373/
https://eprints.nottingham.ac.uk/51373/
https://eprints.nottingham.ac.uk/51373/