Selective inhibitors of cyclo‐oxygenase‐2 (COX‐2) induce hypoalgesia in a rat paw model of inflammation

Francischi, Janetti Nogueira de; Chaves, C T; Moura, None Augusto Brêtas de; Lima, Agnaldo Soares; Rocha, Orivaldo A.; Ferreira-Alves, Dalton L.; Bakhle, Y.S.

doi:10.1038/sj.bjp.0704937

Cited by 83 publications

(78 citation statements)

References 22 publications

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“…Ibuprofen (Sigma, St-Louis, USA), a non-specific COX inhibitor, and rofecoxib, a specific COX-2 inhibitor, were dissolved in 0.9% NaCl solution. For rofecoxib, the compressed tablet from commercial preparations (VIOXX®, 25 mg) was weighed and crushed (using a mortar) into a fine suspension with physiological saline (Francischi et al, 2002). Finally, NS-398 (another specific COX-2 inhibitor) was dissolved in 0.9% NaCl solution containing 4% DMSO and was purchased from Cayman Chemicals (MI, USA).…”

Section: Drug Administrationmentioning

confidence: 99%

“…Indeed, the antinociceptive effect of NSAIDs administered locally has already been reported (Islas-Cadena et al, 1999;Aguirre-Banuelos and Granados-Soto, 2000;Francischi et al, 2002;Torres-Lopez et al, 2002;Ma and Eisenach, 2003), but the antinociceptive efficacy of selective COX-2 inhibitors compared to standard NSAIDs is controversial. In the present study, rofecoxib displayed antinociceptive effects at very low concentrations during the two phases of the formalin test but did not influence paw oedema formation.…”

Section: Local Antinociceptive Effect Of Nsaidsmentioning

confidence: 99%

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Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

Guindon

LoVerme

Léan

et al. 2006

European Journal of Pharmacology

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Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty-acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of anandamide, an endocannabinoid. It has been suggested that the mechanisms of action of NSAIDs could be due to inhibition of cyclooxygenase (COX) and also to an increase in endocannabinoid concentrations. In a previous study we have demonstrated that the local analgesic interaction between anandamide and ibuprofen (a non-specific COX inhibitor) was synergistic for the acute and inflammatory phases of the formalin test. To test this hypothesis further, we repeated similar experiments with rofecoxib (a selective COX-2 inhibitor) and also measured the local concentrations of anandamide, and of two fatty-acid amides, oleoylethanolamide and palmitoylethanolamide. We established the ED 50 for anandamide (34.52 pmol ± 17.26) and rofecoxib (381.72 pmol ± 190.86) and showed that the analgesic effect of the combination was synergistic. We also found that paw tissue levels of anandamide, oleoylethanolamide and palmitoylethanolamide were significantly higher when anandamide was combined with NSAIDs and that this effect was greater with rofecoxib. In conclusion, local injection of anandamide or rofecoxib was antinociceptive in a test of acute and inflammatory pain and the combination of anandamide with rofecoxib was synergistic. Finally, locally injected anandamide with either NSAID (ibuprofen or rofecoxib) generates higher amount of fatty-acid ethanolamides. The exact comprehension of the mechanisms involved needs further investigation.

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Section: Drug Administrationmentioning

confidence: 99%

Section: Local Antinociceptive Effect Of Nsaidsmentioning

confidence: 99%

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

Guindon

LoVerme

Léan

et al. 2006

European Journal of Pharmacology

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“…Interestingly, the nonselective COX inhibitor, indomethacin, produced similar results to those seen with celecoxib [29,30]. The nonselective COX inhibitor, meloxicam, has been reported to actually show preference for COX-2 inhibition [29].…”

Section: Thermal Hyperalgesia (Th) Pain Testmentioning

confidence: 73%

“…In carrageenan-induced paw hyperalgesia studies in rats, pretreatment with rofecoxib or celecoxib significantly increased the mechanically-determined hyperalgesia threshold due to inflammatory responses in the initial 24 hour period post nerve injury [30]. Intraperitoneal administration of the experimental selective COX-2 inhibitor dup 697 to rats with Carrageenan-induced paw hyperalgesia resulted in a significant decrease in mechanical hyperalgesia [40].…”

Section: Discussion Study 1: Indomethacin and Celecoxibmentioning

confidence: 97%

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Immediate administration of COX inhibitors in spinal cord contusion injury and a current review of COX Therapy

Moran¹,

Sampene²,

Oakes³

et al. 2017

Med Res Innov

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Background: Neuropathic pain (NP) is a common complication during the late phase of spinal cord injury (SCI). The enzyme cyclooxygenase-2 (COX-2) shown to play a crucial role during the inflammatory early phase of SCI. We report here on the antihyperalgesic effects of three COX inhibitors: celecoxib, indomethacin and meloxicam used individually. Their efficacy and impact on mortality losses following administration of each treatment evaluated in the late phase of chronic NP post SCI.

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Circadian pattern of spontaneous behavior in monarthritic rats: A novel global approach to evaluation of chronic pain and treatment effectiveness

Millecamps¹,

Jourdan²,

Leger³

et al. 2005

Arthritis & Rheumatism

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Objective. Preclinical evaluation is an essential step in the assessment of new antiinflammatory or analgesic drugs. This study was undertaken to develop a new mode of evaluation of drug effectiveness based on behavior indicating well-being in a rat model of chronic inflammatory pain. We chose to examine the circadian pattern of spontaneous behavior.Methods. The work was performed with a model of chronic monarthritis induced by Freund's complete adjuvant. Variations in behavioral patterns during the time course of arthritis were analyzed. In a second phase, the impact of acetaminophen and 2 nonsteroidal antiinflammatory drugs (aspirin and celecoxib), which are currently used in clinical practice to treat chronic inflammation, was studied after 7 days of treatment.Results. The nocturnal pattern of activity of healthy rats comprised 3 main bursts. Chronic painful monarthritis altered this spontaneous pattern of nocturnal behavior (normal period of activity). Monarthritic rats showed a decrease in the total time spent in activity during the night, and lost their pattern of activity. These behavioral disturbances were reversed after long-term treatment with acetaminophen or celecoxib, with celecoxib appearing to be more effective. Aspirin was ineffective.Conclusion. These results enabled us to test this new procedure as a means of assessing well-being or illbeing during stages of chronic inflammatory pain in rats, and the effectiveness of repeated pharmacologic treatments.Arthritis and other rheumatic conditions are among the most common chronic diseases: they affected 70 million US adults in 2001, and are the major cause of disability among US adults (60% of US population older than 65 years) (1). These conditions are characterized by persistent inflammatory pain, which is treated with nonsteroidal antiinflammatory drugs or corticosteroids (2). However, long-term use of these drugs induces numerous gastrointestinal side effects (3,4), and their real impact on patient quality of life remains uncertain.The search for new pharmacologic treatments for these conditions continues (5-9), but preclinical evaluation of their effectiveness has lagged behind. The predictive ability of current techniques used to assess drug effectiveness remains approximate because they are based on reflex (10-12) or pseudo-affective (13,14) reactions to acute or subacute painful stimuli in animals, which have limited relevance to predictability in humans. Investigators have attempted to identify specific behaviors as markers of discomfort generated by pain (paw position [15], weight load on each leg [16], gait analysis [17], or locomotion [18]). However, there is only putative evidence that they may be of use in pharmacologic studies since they adopt a functional approach to disease rather than constituting a real evaluation of spontaneous pain.Many clinical studies on pain are based on genSupported by a grant from the Association pour la Recherche sur la Poly-arthrite.

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Selective inhibitors of cyclo‐oxygenase‐2 (COX‐2) induce hypoalgesia in a rat paw model of inflammation

Cited by 83 publications

References 22 publications

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

Immediate administration of COX inhibitors in spinal cord contusion injury and a current review of COX Therapy

Circadian pattern of spontaneous behavior in monarthritic rats: A novel global approach to evaluation of chronic pain and treatment effectiveness

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