Superoxide anion-induced pain and inflammation depends on TNFα/TNFR1 signaling in mice

Yamacita-Borin, Fabiane Y.; Zarpelon, Ana C.; Pinho‐Ribeiro, Felipe A.; Fattori, Victor; Alves‐Filho, José C.; Cunha, Fernando Q.; Cunha, Thiago M.; Casagrande, Rúbia; Verri, Waldiceu A.

doi:10.1016/j.neulet.2015.08.015

Cited by 36 publications

(31 citation statements)

References 29 publications

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“…Prohyperalgesic cytokines such as TNF α and IL-1 β contribute to nociceptor neuron sensitization [7, 30] and cytokines such as IL-10 limit the development of hyperalgesia by inhibiting the production of hyperalgesic cytokines [31]. Therefore, the effect of tempol on KO 2 -induced cytokine production was evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…In fact, NF- κ B activation has been implicated in de novo superoxide anion production [38] and TLR4/myeloid differentiation primary response gene 88 (MyD88) activation induces inflammatory pain [39]. Cytokines such as TNF α and IL-1 β can activate NADPH oxidase inducing superoxide anion production [40, 41], and TNF α /TNFR1 signaling mediates superoxide anion-triggered pain and oxidative stress and TNF α -induced hyperalgesia depends on superoxide anion [7]. In addition to proinflammatory cytokines, there is the participation of anti-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…injection, and mechanical hyperalgesia and thermal hyperalgesia were evaluated always 30 min after treatment from 1 to 7 days. The dose of carrageenan, CFA, and KO 2 and time points chosen for the experimental protocol were determined according to previous studies of our laboratory [7, 20–23]. …”

Section: Methodsmentioning

confidence: 99%

“…After being recruited into the inflammatory focus, neutrophils are activated by these signals, including the activation of the so-called respiratory burst represented by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase membrane-bound enzyme complex production of superoxide anion in neutrophils. This scenario characterized by the exacerbation of superoxide anion production propagates the inflammatory response resulting in sensitization of primary nociceptive neurons [7]. The terminal endings of nociceptive neurons are widespread in all tissues, where they identify noxious (intense) stimuli, including trauma, chemicals, heat, and cold.…”

Section: Introductionmentioning

confidence: 99%

“…The beneficial biological effects of tempol range from protective effects against radiation, metabolic syndrome, and shock as well as heart, kidney, and central nervous system safekeeping [12]. Tempol inhibits superoxide anion-induced neuronal firing, thermal hyperalgesia, and edema induced by carrageenan, neuropathic pain induced by chronic constriction injury (CCI) [13–15] and chemotherapy [16] in rats, and TNF α -induced mechanical hyperalgesia and neutrophils recruitment in mice [7]. Tempol treatment also eliminates free radicals and inhibits lipid peroxidation in vitro and in vivo [15, 17–19].…”

Section: Introductionmentioning

confidence: 99%

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Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

Bernardy

Zarpelon

Pinho‐Ribeiro

et al. 2017

BioMed Research International

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The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10–100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

Bernardy

Zarpelon

Pinho‐Ribeiro

et al. 2017

BioMed Research International

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Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice

et al. 2018

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The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.

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Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress

et al. 2016

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We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

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Superoxide anion-induced pain and inflammation depends on TNFα/TNFR1 signaling in mice

Cited by 36 publications

References 29 publications

Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice

Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress

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