Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing

Hiroshi Hoshijima,1 Matthew Hunt,2 Hiroshi Nagasaka,1 Tony Yaksh2 1Department of Anesthesiology, Saitama Medical University Hospital, Saitama, Japan; 2Departments of Anesthesiology and Pharmacology, University of California, San Diego Anesthesia Research Laboratory, La Jolla, CA, USACorrespondence:...

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Autores principales:	Hoshijima H, Hunt M, Nagasaka H, Yaksh T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	intrathecal paracetamol cannabinoid serotonin anandamide analgesia Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0a274b111ac04f29b863f73f08b09130
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spelling	oai:doaj.org-article:0a274b111ac04f29b863f73f08b091302021-11-14T19:00:30ZSystematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing1178-7090https://doaj.org/article/0a274b111ac04f29b863f73f08b091302021-11-01T00:00:00Zhttps://www.dovepress.com/systematic-review-of-systemic-and-neuraxial-effects-of-acetaminophen-i-peer-reviewed-fulltext-article-JPRhttps://doaj.org/toc/1178-7090Hiroshi Hoshijima,1 Matthew Hunt,2 Hiroshi Nagasaka,1 Tony Yaksh2 1Department of Anesthesiology, Saitama Medical University Hospital, Saitama, Japan; 2Departments of Anesthesiology and Pharmacology, University of California, San Diego Anesthesia Research Laboratory, La Jolla, CA, USACorrespondence: Tony YakshDepartments of Anesthesiology and Pharmacology, University of California, San Diego Anesthesia Research Laboratory 0818, 9500 Gilman Dr., La Jolla, CA, 92093, USATel +1 619-543-3597Fax +1 619-543-6070Email tyaksh@health.ucsd.eduAbstract: Acetaminophen (APAP) in humans has robust effects with a high therapeutic index in altering postoperative and inflammatory pain states in clinical and experimental pain paradigms with no known abuse potential. This review considers the literature reflecting the preclinical actions of acetaminophen in a variety of pain models. Significant observations arising from this review are as follows: 1) acetaminophen has little effect upon acute nociceptive thresholds; 2) acetaminophen robustly reduces facilitated states as generated by mechanical and thermal hyperalgesic end points in mouse and rat models of carrageenan and complete Freund’s adjuvant evoked inflammation; 3) an antihyperalgesic effect is observed in models of facilitated processing with minimal inflammation (eg, phase II intraplantar formalin); and 4) potent anti-hyperpathic effects on the thermal hyperalgesia, mechanical and cold allodynia, allodynic thresholds in rat and mouse models of polyneuropathy and mononeuropathies and bone cancer pain. These results reflect a surprisingly robust drug effect upon a variety of facilitated states that clearly translate into a wide range of efficacy in preclinical models and to important end points in human therapy. The specific systems upon which acetaminophen may act based on targeted delivery suggest both a spinal and a supraspinal action. Review of current targets for this molecule excludes a role of cyclooxygenase inhibitor but includes effects that may be mediated through metabolites acting on the TRPV1 channel, or by effect upon cannabinoid and serotonin signaling. These findings suggest that the mode of action of acetaminophen, a drug with a long therapeutic history of utilization, has surprisingly robust effects on a variety of pain states in clinical patients and in preclinical models with a good therapeutic index, but in spite of its extensive use, its mechanisms of action are yet poorly understood.Keywords: intrathecal, paracetamol, cannabinoid, serotonin, anandamide, analgesiaHoshijima HHunt MNagasaka HYaksh TDove Medical PressarticleintrathecalparacetamolcannabinoidserotoninanandamideanalgesiaMedicine (General)R5-920ENJournal of Pain Research, Vol Volume 14, Pp 3521-3552 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intrathecal paracetamol cannabinoid serotonin anandamide analgesia Medicine (General) R5-920
spellingShingle	intrathecal paracetamol cannabinoid serotonin anandamide analgesia Medicine (General) R5-920 Hoshijima H Hunt M Nagasaka H Yaksh T Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing
description	Hiroshi Hoshijima,1 Matthew Hunt,2 Hiroshi Nagasaka,1 Tony Yaksh2 1Department of Anesthesiology, Saitama Medical University Hospital, Saitama, Japan; 2Departments of Anesthesiology and Pharmacology, University of California, San Diego Anesthesia Research Laboratory, La Jolla, CA, USACorrespondence: Tony YakshDepartments of Anesthesiology and Pharmacology, University of California, San Diego Anesthesia Research Laboratory 0818, 9500 Gilman Dr., La Jolla, CA, 92093, USATel +1 619-543-3597Fax +1 619-543-6070Email tyaksh@health.ucsd.eduAbstract: Acetaminophen (APAP) in humans has robust effects with a high therapeutic index in altering postoperative and inflammatory pain states in clinical and experimental pain paradigms with no known abuse potential. This review considers the literature reflecting the preclinical actions of acetaminophen in a variety of pain models. Significant observations arising from this review are as follows: 1) acetaminophen has little effect upon acute nociceptive thresholds; 2) acetaminophen robustly reduces facilitated states as generated by mechanical and thermal hyperalgesic end points in mouse and rat models of carrageenan and complete Freund’s adjuvant evoked inflammation; 3) an antihyperalgesic effect is observed in models of facilitated processing with minimal inflammation (eg, phase II intraplantar formalin); and 4) potent anti-hyperpathic effects on the thermal hyperalgesia, mechanical and cold allodynia, allodynic thresholds in rat and mouse models of polyneuropathy and mononeuropathies and bone cancer pain. These results reflect a surprisingly robust drug effect upon a variety of facilitated states that clearly translate into a wide range of efficacy in preclinical models and to important end points in human therapy. The specific systems upon which acetaminophen may act based on targeted delivery suggest both a spinal and a supraspinal action. Review of current targets for this molecule excludes a role of cyclooxygenase inhibitor but includes effects that may be mediated through metabolites acting on the TRPV1 channel, or by effect upon cannabinoid and serotonin signaling. These findings suggest that the mode of action of acetaminophen, a drug with a long therapeutic history of utilization, has surprisingly robust effects on a variety of pain states in clinical patients and in preclinical models with a good therapeutic index, but in spite of its extensive use, its mechanisms of action are yet poorly understood.Keywords: intrathecal, paracetamol, cannabinoid, serotonin, anandamide, analgesia
format	article
author	Hoshijima H Hunt M Nagasaka H Yaksh T
author_facet	Hoshijima H Hunt M Nagasaka H Yaksh T
author_sort	Hoshijima H
title	Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing
title_short	Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing
title_full	Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing
title_fullStr	Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing
title_full_unstemmed	Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing
title_sort	systematic review of systemic and neuraxial effects of acetaminophen in preclinical models of nociceptive processing
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/0a274b111ac04f29b863f73f08b09130
work_keys_str_mv	AT hoshijimah systematicreviewofsystemicandneuraxialeffectsofacetaminopheninpreclinicalmodelsofnociceptiveprocessing AT huntm systematicreviewofsystemicandneuraxialeffectsofacetaminopheninpreclinicalmodelsofnociceptiveprocessing AT nagasakah systematicreviewofsystemicandneuraxialeffectsofacetaminopheninpreclinicalmodelsofnociceptiveprocessing AT yaksht systematicreviewofsystemicandneuraxialeffectsofacetaminopheninpreclinicalmodelsofnociceptiveprocessing
_version_	1718428964293181440

Systematic Review of Systemic and Neuraxial Effects of Acetaminophen in Preclinical Models of Nociceptive Processing

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