Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord

PLoS One. 2015 Mar 30;10(3):e0118942. doi: 10.1371/journal.pone.0118942. eCollection 2015.

Abstract

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrageenan / toxicity
  • Cytokines / genetics
  • Cytokines / metabolism
  • Extremities / physiopathology
  • Glutathione / metabolism
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Male
  • Mice
  • NF-kappa B / metabolism*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology
  • Superoxides / metabolism
  • Vinca Alkaloids / pharmacology
  • Vinca Alkaloids / therapeutic use*

Substances

  • Cytokines
  • NF-kappa B
  • Neuroprotective Agents
  • Vinca Alkaloids
  • Superoxides
  • vinpocetine
  • Carrageenan
  • Glutathione

Grants and funding

This work was supported by Brazilian grants from Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Ministério da Ciência, Tecnologia e Inovação (MCTI)/ Secretaria da Ciência, Tecnologia e Inovação (SETI)/ Fundação Araucária, and Paraná State Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.