Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis

McQueen, Daniel S.; Iggo, A.; Birrell, G.J.; Grubb, Blair D.

doi:10.1111/j.1476-5381.1991.tb12404.x

Cited by 43 publications

(19 citation statements)

References 19 publications

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“…The lack of antiinflammatory activity by "aniline analgesics" has been questioned by some investigators. Their claims were supported in part by experimental (1,2,133,219,231) and clinical (126,193,194) data.…”

Section: Pharmacological Effectsmentioning

confidence: 87%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB 1 receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB 1 receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB 1 receptor agonist, completely prevents the analgesic ac- 250CNS Drug Reviews Vol. 12, No. 3-4, pp. 250-275 © 2006 tivity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB 1 agonists are being introduced for pain treatment, it comes out that an indirect cannabinomimetic had been extensively used (and sometimes overused) for more than a century.

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Section: Pharmacological Effectsmentioning

confidence: 87%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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“…Activation of nociceptors is central to the experience of pain, and several chronic pain conditions are caused by the sensitization of nociceptors to mechanical stimuli, including osteoarthritis and rheumatoid arthritis pain (He et al, 2017;McQueen et al, 1991;Neogi et al, 2016;Okun et al, 2012;Schaible, 2014). Intervening at the level of primary afferent nociceptors is a promising approach to developing therapeutic treatments.…”

Section: Discussionmentioning

confidence: 99%

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

Beaulieu-Laroche

Christin

Donoghue

et al. 2018

Preprint

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“…Tissue injury results in the release of various chemical substances, including prostaglandins (PGs), which may sensitize the nociceptors to pain mediators (eg histamine, bradykinin, 5-hydroxytryptamine). Thus, the analgesic effect of these drugs might be ascribed to their ability to inhibit the cyclo-oxygenase activity in the periphery (Capetola et al, 1983;McQueen et al, 1991). However, this mode of action has been questioned (McCormack and Brune, 1991).…”

Section: Peripherally Acting Analgesicsmentioning

confidence: 99%

Central analgesic effects of aspirin‐like drugs

Bannwarth

Demotes‐Mainard

Schaeverbeke

et al. 1995

Fundamemntal Clinical Pharma

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Aspirin-like drugs mainly include paracetamol, salicylates and other non-steroidal anti-inflammatory drugs, and metamizole. Their analgesic effect is classically ascribed to a peripheral site of action, within the pain-processing site. There is, however, convincing evidence that a central component contributes to the overall analgesia provided by these agents. Experimental and clinical studies referring to this challenging proposal are reviewed here. The exact site and mode of action of aspirin-like drugs within the central nervous system remains controversial. It is likely that supraspinal mechanisms play an important role. Some experiments lend support to the involvement of monoaminergic control systems. Other data indicate that these drugs act centrally through the inhibition of cyclo-oxygenase activity. The interactions between prostaglandins and various neurotransmitters suggest that both mechanisms may be linked.

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Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis

Cited by 43 publications

References 19 publications

Paracetamol: New Vistas of an Old Drug

Paracetamol: New Vistas of an Old Drug

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

Central analgesic effects of aspirin‐like drugs

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