Blockade of leukotriene B4 prevents articular incapacitation in rat zymosan-induced arthritis

Rocha, Francisco Airton Castro da; Teixeira, Mauro M.; Rocha, José Geraldo; Girão-Carmona, Virgínia Cláudia Carneiro; Bezerra, Mirna Marques; Ribeiro, Ronaldo de Albuquerque; Cunha, Fernando

doi:10.1016/j.ejphar.2004.06.025

Cited by 21 publications

(18 citation statements)

References 21 publications

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“…Indirect evidence for the involvement of neutrophils in inflammatory hypernociception was demonstrated in zymosan-induced joint inflammation. In this model, the articular movement incapacitation was inhibited by the LT synthesis inhibitor, which also decreased the neutrophil accumulation into the joints [53]. Furthermore, Lavich et al [24] recently showed that neutrophils played a crucial role in thermal hypernociception in- A and B, respectively).…”

Section: Discussionmentioning

confidence: 94%

Crucial role of neutrophils in the development of mechanical inflammatory hypernociception

Cunha

Verri

Schivo

et al. 2008

Journal of Leukocyte Biology

290

206

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Neutrophil migration is responsible for tissue damage observed in inflammatory diseases. Neutrophils are also implicated in inflammatory nociception, but mechanisms of their participation have not been elucidated. In the present study, we addressed these mechanisms in the carrageenan-induced mechanical hypernociception, which was determined using a modification of the Randall-Sellito test in rats. Neutrophil accumulation into the plantar tissue was determined by the contents of myeloperoxidase activity, whereas cytokines and PGE(2) levels were measured by ELISA and radioimmunoassay, respectively. The pretreatment of rats with fucoidin (a leukocyte adhesion inhibitor) inhibited carrageenan-induced hypernociception in a dose- and time-dependent manner. Inhibition of hypernociception by fucoidin was associated with prevention of neutrophil recruitment, as it did not inhibit the hypernociception induced by the direct-acting hypernociceptive mediators, PGE(2) and dopamine, which cause hypernociception, independent of neutrophils. Fucoidin had no effect on carrageenan-induced TNF-alpha, IL-1beta, and cytokine-induced neutrophil chemoattractant 1 (CINC-1)/CXCL1 production, suggesting that neutrophils were not the source of hypernociceptive cytokines. Conversely, hypernociception and neutrophil migration induced by TNF-alpha, IL-1beta, and CINC-1/CXCL1 was inhibited by fucoidin, suggesting that neutrophils are involved in the production of direct-acting hypernociceptive mediators. Indeed, neutrophils stimulated in vitro with IL-1beta produced PGE(2), and IL-1beta-induced PGE(2) production in the rat paw was inhibited by the pretreatment with fucoidin. In conclusion, during the inflammatory process, the migrating neutrophils participate in the cascade of events leading to mechanical hypernociception, at least by mediating the release of direct-acting hypernociceptive mediators, such as PGE(2). Therefore, the blockade of neutrophil migration could be a target to development of new analgesic drugs.

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Section: Discussionmentioning

confidence: 94%

Crucial role of neutrophils in the development of mechanical inflammatory hypernociception

Cunha

Verri

Schivo

et al. 2008

Journal of Leukocyte Biology

290

206

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“…In the knee joint, zymosan is able to simulate an inflammatory response like that observed in the arthritis development, in which both resident synovial and infiltrated immune cells produce several mediators of inflammation, including nitrogen and oxygen-derived free radicals, cytokines, leukotrienes, and prostaglandins, which have been associated with the degradation of articular cartilage (4,46,47). Frasnelli et al (19) demonstrated that Toll-like receptor (TLR) 2 is the major pathway of proinflammatory signaling in zymosan-induced arthritis in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Frasnelli et al (19) demonstrated that Toll-like receptor (TLR) 2 is the major pathway of proinflammatory signaling in zymosan-induced arthritis in mice. Furthermore, this stimulus has been used in the investigation of other aspects of arthritis-associated inflammatory response, including loss of mobility, articular hyperalgesia, edema, and fever (20,21,46,47,52).…”

Section: Discussionmentioning

confidence: 99%

“…In this test, a computerassisted device measures the length of time that a specific hind paw fails to touch the surface of a rotating cylinder in a 1-min period (paw elevation time). Normally, animal paw elevation time is ϳ10 -15 s. In previous experiments, incapacitation was studied in animals injected with zymosan (1 mg/animal) (47,58) into the knee joints, and in the present study, we have modified this dose to 4 mg/cavity. The period for which the hind paw failed to touch the rotating cylinder was interpreted as being proportional to the pain felt by the animal.…”

Section: Methodsmentioning

confidence: 99%

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Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Kanashiro¹,

Pessini²,

Machado³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Kanashiro A, Pessini AC, Machado RR, Malvar DC, Aguiar FA, Soares DM, Vale ML, Souza GEP. Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats. Am J Physiol Regul Integr Comp Physiol 296: R1631-R1640, 2009. First published February 25, 2009 doi:10.1152/ajpregu.90527.2008.-The present study investigated the febrile response in zymosan-induced arthritis, as well as the increase in PGE2 concentration in the cerebrospinal fluid (CSF), along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articularly injected at the dose of 0.5 mg did not affect the body core temperature (Tc) compared with saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long-lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h, and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature, as well as hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE 2 concentration in the CSF but not in the plasma. Oral pretreatment with ibuprofen (5-20 mg/kg), celecoxib (1-10 mg/kg), dipyrone (60 -240 mg/kg), and paracetamol (100 -200 mg/kg) or subcutaneous injection of dexamethasone (0.25-1.0 mg/kg) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg/kg), paracetamol (150 mg/kg), and dipyrone (120 mg/kg) decreased CSF PGE 2 concentration and fever during zymosan-induced arthritis, suggesting the involvement of PGE2 in this response.

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“…As NDGA is a non-selective lipoxygenase inhibitor, peripherally formed products of 5-lipoxygenase (leukotrienes), 12-and/or 15-lipoxygenase may equally be involved. Consistent with the proposed pro-nociceptive role of lipoxygenase products, leukotriene B 4 (LTB 4 ), LTD 4 and other lipoxygenase products were shown to exert pronociceptive effects in various animal models (Levine et al 1984;Martin et al 1987;Cunha et al 2003;Rocha et al 2004;Singh et al 2005;Taylor-Clark et al 2008).…”

Section: Discussionmentioning

confidence: 68%

Comparison of the peripheral mediator background of heat injury- and plantar incision-induced drop of the noxious heat threshold in the rat

et al. 2010

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Blockade of leukotriene B4 prevents articular incapacitation in rat zymosan-induced arthritis

Cited by 21 publications

References 21 publications

Crucial role of neutrophils in the development of mechanical inflammatory hypernociception

Crucial role of neutrophils in the development of mechanical inflammatory hypernociception

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Comparison of the peripheral mediator background of heat injury- and plantar incision-induced drop of the noxious heat threshold in the rat

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