Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia

Abstract. Introduction:. Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises. Objectives:. We tested the hypothesis that t...

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Autores principales:	Amanda Lillywhite, Stephen G. Woodhams, Sara V. Gonçalves, David J.G. Watson, Li Li, James J. Burston, Peter R.W. Gowler, Meritxell Canals, David A. Walsh, Gareth J. Hathway, Victoria Chapman
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer 2021
Materias:	Anesthesiology RD78.3-87.3
Acceso en línea:	https://doaj.org/article/5ec1331b06bf473e8821f26c427d8514
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spelling	oai:doaj.org-article:5ec1331b06bf473e8821f26c427d85142021-11-25T07:59:39ZAnxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia2471-253110.1097/PR9.0000000000000956https://doaj.org/article/5ec1331b06bf473e8821f26c427d85142021-11-01T00:00:00Zhttp://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000956https://doaj.org/toc/2471-2531Abstract. Introduction:. Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises. Objectives:. We tested the hypothesis that the interaction between anxiety, chronic pain, and opioid use results from altered endogenous opioid function. Methods:. A genetic model of negative affect, the Wistar–Kyoto (WKY) rat, was combined with intra-articular injection of monosodium iodoacetate (MIA; 1 mg) to mimic clinical presentation. Effects of systemic morphine (0.5–3.5 mg·kg−1) on pain behaviour and spinal nociceptive neuronal activity were compared in WKY and normo-anxiety Wistar rats 3 weeks after MIA injection. Endogenous opioid function was probed by the blockade of opioid receptors (0.1–1 mg·kg−1 systemic naloxone), quantification of plasma β-endorphin, and expression and phosphorylation of spinal mu-opioid receptor (MOR). Results:. Monosodium iodoacetate–treated WKY rats had enhanced OA-like pain, blunted morphine-induced analgesia, and greater mechanical hypersensitivity following systemic naloxone, compared with Wistar rats, and elevated plasma β-endorphin levels compared with saline-treated WKY controls. Increased MOR phosphorylation at the master site (serine residue 375) in the spinal cord dorsal horn of WKY rats with OA-like pain (P = 0.0312) indicated greater MOR desensitization. Conclusions:. Reduced clinical analgesic efficacy of morphine was recapitulated in a model of high anxiety and OA-like pain, in which endogenous opioid tone was altered, and MOR function attenuated, in the absence of previous exogenous opioid ligand exposure. These findings shed new light on the mechanisms underlying the increased opioid analgesic use in high anxiety patients with chronic pain.Amanda LillywhiteStephen G. WoodhamsSara V. GonçalvesDavid J.G. WatsonLi LiJames J. BurstonPeter R.W. GowlerMeritxell CanalsDavid A. WalshGareth J. HathwayVictoria ChapmanWolters KluwerarticleAnesthesiologyRD78.3-87.3ENPAIN Reports, Vol 6, Iss 4, p e956 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Anesthesiology RD78.3-87.3
spellingShingle	Anesthesiology RD78.3-87.3 Amanda Lillywhite Stephen G. Woodhams Sara V. Gonçalves David J.G. Watson Li Li James J. Burston Peter R.W. Gowler Meritxell Canals David A. Walsh Gareth J. Hathway Victoria Chapman Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
description	Abstract. Introduction:. Negative affect, including anxiety and depression, is prevalent in chronic pain states such as osteoarthritis (OA) and associated with greater use of opioid analgesics, potentially contributing to present and future opioid crises. Objectives:. We tested the hypothesis that the interaction between anxiety, chronic pain, and opioid use results from altered endogenous opioid function. Methods:. A genetic model of negative affect, the Wistar–Kyoto (WKY) rat, was combined with intra-articular injection of monosodium iodoacetate (MIA; 1 mg) to mimic clinical presentation. Effects of systemic morphine (0.5–3.5 mg·kg−1) on pain behaviour and spinal nociceptive neuronal activity were compared in WKY and normo-anxiety Wistar rats 3 weeks after MIA injection. Endogenous opioid function was probed by the blockade of opioid receptors (0.1–1 mg·kg−1 systemic naloxone), quantification of plasma β-endorphin, and expression and phosphorylation of spinal mu-opioid receptor (MOR). Results:. Monosodium iodoacetate–treated WKY rats had enhanced OA-like pain, blunted morphine-induced analgesia, and greater mechanical hypersensitivity following systemic naloxone, compared with Wistar rats, and elevated plasma β-endorphin levels compared with saline-treated WKY controls. Increased MOR phosphorylation at the master site (serine residue 375) in the spinal cord dorsal horn of WKY rats with OA-like pain (P = 0.0312) indicated greater MOR desensitization. Conclusions:. Reduced clinical analgesic efficacy of morphine was recapitulated in a model of high anxiety and OA-like pain, in which endogenous opioid tone was altered, and MOR function attenuated, in the absence of previous exogenous opioid ligand exposure. These findings shed new light on the mechanisms underlying the increased opioid analgesic use in high anxiety patients with chronic pain.
format	article
author	Amanda Lillywhite Stephen G. Woodhams Sara V. Gonçalves David J.G. Watson Li Li James J. Burston Peter R.W. Gowler Meritxell Canals David A. Walsh Gareth J. Hathway Victoria Chapman
author_facet	Amanda Lillywhite Stephen G. Woodhams Sara V. Gonçalves David J.G. Watson Li Li James J. Burston Peter R.W. Gowler Meritxell Canals David A. Walsh Gareth J. Hathway Victoria Chapman
author_sort	Amanda Lillywhite
title	Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
title_short	Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
title_full	Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
title_fullStr	Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
title_full_unstemmed	Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
title_sort	anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia
publisher	Wolters Kluwer
publishDate	2021
url	https://doaj.org/article/5ec1331b06bf473e8821f26c427d8514
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Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia

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