Journal
INFLAMMOPHARMACOLOGY
Volume 24, Issue 2-3, Pages 97-107Publisher
SPRINGER BASEL AG
DOI: 10.1007/s10787-016-0266-3
Keywords
Pyrrolidine dithiocarbamate; Superoxide anion; NF-kappa B ; Oxidative stress; Inflammation; Pain; Cytokine; Dorsal root ganglia reflex
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Funding
- Sao Paulo Research Foundation (FAPESP) [2011/19670-0, 2013/08216-2]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Ministerio da Ciencia, Tecnologia e Inovacao (MCTI)
- Secretaria da Ciencia, Tecnologia e Ensino Superior (SETI)
- Fundacao Araucaria
- Parana State Government
- CAPES/Fundacao Araucaria
- CAPES
- CNPq
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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-kappa B and increased cytokine production (IL-1 beta, TNF-alpha 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-kappa B 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-kappa B-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.
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