Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats
Abstract
Experiments were performed in carrageenin-treated rats to study, the antinociceptive and anti-inflammatory effects of paracetamol intravenously (i.v.) or intrathecally (i.t.) injected on rats submitted to a mechanical noxious stimulus. The influence of intrathecal tropisetron, a 5 hydroxytryptamine(3) (5-HT(3)) receptor antagonist, on the antinociceptive effects of paracetamol, was also studied. Paracetamol induced a significant antinociceptive effect after (100, 200 and 300 mg/kg) i.v. and (50, 100 and 200 microg/rat) i.t. injection, but no change occurred on edema volume. The effect of paracetamol was totally inhibited by tropisetron (10 microg/rat, i.t.). The foregoing results demonstrate that, in conditions of inflammatory pain, paracetamol exerts a central antinociceptive effect involving spinal 5-HT(3) receptors, without inducing any anti-inflammatory action. These data, give further arguments to consider paracetamol as a central analgesic drug which must be distinguished from non-steroidal anti-inflammatory drugs (NSAIDs), which justifies the usual combination of paracetamol in post-operative pain.
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The involvement of the serotonergic pathway in paracetamol action stems from increasing 5-TH levels in central structures and activating spinal 5-TH receptors.
“The involvement of the serotonergic pathway in paracetamol action was reported to stem from increasing 5-TH levels in the central structures and activating the spinal 5-TH receptors.60–71”
Selective blockade of particular serotonergic receptors abolishes the analgesic actions of paracetamol in acute models of pain.
“Decades of research have provided evidence on the significance of this pathway to mediate the analgesic action of paracetamol as it has been shown that selective blockade of particular serotonergic receptors to abolish the analgesic actions of paracetamol in acute models of pain.”
From Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action (2021) · cites this paper as [80]
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- Authors
- Alloui, A., Chassaing, C., Schmidt, J., Ardid, D., Dubray, C., Cloarec, A., & Eschalier, A.
- Affiliations
- Inserm (FR)
- Bristol-Myers Squibb (France) (FR)
- Corresponding author
- Alloui, Abdelkrim
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 443
- Issue
- 1-3
- Pages
- 71-77
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2140002787
- Cited by
- 83
- References
- 39
- Citations by year
- 2024: 1 · 2023: 3 · 2021: 6 · 2020: 9 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 6
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- paracetamol, antinociception, inflammatory pain, tropisetron, intrathecal administration, carrageenan-induced edema, central analgesia, postoperative pain, nonsteroidal anti-inflammatory drugs
- MeSH terms
- Tropisetron, Acetaminophen, Animals, Anti-Inflammatory Agents, Non-Steroidal, Drug Interactions, Edema, Indoles, Inflammation, Injections, Intravenous, Injections, Spinal, Male, Pain, Receptors, Serotonin, Rats, Sprague-Dawley, Receptors, Serotonin, 5-HT3, Rats
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