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

Hoshijima, Hiroshi; Hunt, Matt; Nagasaka, Hiroshi; Yaksh, Tony L.

doi:10.2147/jpr.s308028

Cited by 9 publications

(5 citation statements)

References 215 publications

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“…TRPA1 is the most polymodal receptor channel of all TRPs, activated or inhibited by hundreds of natural and synthetic chemicals including common drugs such as dipyrone (metamizol) and acetaminophen (paracetamol), the latter accounting for analgesic and antipyretic effects [61,77,119,149], and somehow contributes to noxious heat and cold transduction [74,110,154]. Particular chemical cases are cigarette smoke and its nicotine-free gaseous phase, tissue acidosis activating only the human TRPA1 but not rodent and non-human primate homologs, and nitroxyl anion (H + NO − ) which results from the chemically unusual interaction of the two gasotransmitters H 2 S and NO.…”

Section: Trpa1 Almost Universal Chemosensor and Polymodal Receptormentioning

confidence: 99%

Nobel somatosensations and pain

Reeh

Fischer

2022

Pflugers Arch - Eur J Physiol

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The Nobel prices 2021 for Physiology and Medicine have been awarded to David Julius and Ardem Patapoutian "for their discoveries of receptors for temperature and touch", TRPV1 and PIEZO1/2. The present review tells the past history of the capsaicin receptor, covers further selected TRP channels, TRPA1 in particular, and deals with mechanosensitivity in general and mechanical hyperalgesia in particular. Other achievements of the laureates and translational aspects of their work are shortly treated.

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Section: Trpa1 Almost Universal Chemosensor and Polymodal Receptormentioning

confidence: 99%

Nobel somatosensations and pain

Reeh

Fischer

2022

Pflugers Arch - Eur J Physiol

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“…We have previously shown an involvement of substance P in carrageenan-induced inflammation in mice [ 22 ]. The role of CGRP in carrageenan-induced inflammation has not been fully investigated, although the hyperalgesic role of CGRP in the carrageenan model is clear [ 43 ]. There is evidence from the rat that suggests that CGRP is not involved in carrageenan-induced inflammation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Ability of CGRP to Modulate Microvascular Events in Mouse Skin

Zarban

Chaudhry

Valente

et al. 2022

IJMS

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Oedema formation and polymorphonuclear leukocyte (neutrophil) accumulation are involved in both acute and chronic inflammation. Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide that is released from stimulated sensory nerves. CGRP is a potent vasodilator neuropeptide, especially when administered to the cutaneous microvasculature, with a long duration of action. Here, we have investigated the ability of vasodilator amounts of CGRP to modulate oedema formation and neutrophil accumulation induced in the cutaneous microvasculature of the mouse. To learn more about the mechanism of action of endogenous CGRP, we have investigated the response to the inflammatory stimulants tumour necrosis factor alpha (TNFα) and carrageenan in three different murine models: a model where sensory nerves were depleted by resiniferatoxin (RTX); a pharmacological method to investigate the effect of a selective CGRP receptor antagonist; and a genetic approach using wildtype (WT) and αCGRP knockout (KO) mice. Our results show that exogenous CGRP potentiates oedema formation induced by substance P (SP) and TNFα. This is further supported by our findings from sensory nerve-depleted mice (in the absence of all neuropeptides), which indicated that sensory nerves are involved in mediating the oedema formation and neutrophil accumulation induced by TNFα, and also carrageenan in cutaneous microvasculature. Furthermore, endogenous CGRP was shown to contribute to this inflammatory response as carrageenan-induced oedema formation is attenuated in WT mice treated with the CGRP receptor antagonist, and in αCGRPKO mice. It is therefore concluded that CGRP can contribute to inflammation by promoting oedema formation in skin, but this response is dependent on the pro-inflammatory stimulus and circumstance.

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“…Paracetamol has an effective analgesic action with a high therapeutic index in postoperative and inflammatory pain, with no known abuse potential 17,[26][27][28] . It is the most widely used pain reliever in the United States, where it is taken by about 50 million Americans every week 29 .…”

Section: Discussionmentioning

confidence: 99%

Pain: the use of paracetamol in multimorbid patients

Salamone¹

2022

MAJ

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Introduction: More than one third of Italians have at least 2 chronic comorbidities, and this percentage is more than 50% after the age of 75 years. The presence of comorbidities has as a consequence politreatments, with a high probability of drug interactions and adverse events.Methods: Medical literature about physiopathology of pain and its treatments was reviewed and combined with expert opinion of the authors. Results: Pain is “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”. Chronic pain is one of the main factors that impact on quality of life and is the leading reason why patients seek medical care.Pain can represent a defense against potential or real damage to the body, but chronic pain becomes a disease itself, with a profound negative impact on quality of life. Paracetamol is a drug with analgesic and antipyretic action widely used both alone and in combination with other medications. It is an effective and safe drug, and can be used in infants and elderly, in patients in whom NSAIDs are contraindicated, in pregnant or breastfeeding women. A large number of studies have recognized the efficacy and safety of paracetamol in treating pain, and the drug is included in the WHO’s List of Essential Medicines. EULAR, AAOS and NICE guidelines recommend paracetamol as the first-choice analgesic in several condi- tions like osteoarthritis or post-surgical pain. Conclusions: Paracetamol, due to its efficacy, safety of use, poor interaction with other drugs, appears to be the first- choice treatment of painful syndromes in the elderly patient.

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

Cited by 9 publications

References 215 publications

Nobel somatosensations and pain

Nobel somatosensations and pain

Elucidating the Ability of CGRP to Modulate Microvascular Events in Mouse Skin

Pain: the use of paracetamol in multimorbid patients

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