Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

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.

Evaluation of Therapeutic Efficacy of Vinpocetine in Adjuvant Induced Arthritis Model in Rats

“…The present study indicated that vinpo treatment alone (in a dose of 20 mg/kg) caused a significant inhibition in the levels of TNF-α and IL-1β by 54.88% and 61.89% respectively as compared to the non-treated group. This is in agreement with the previous clinical study done by Ruiz-Miyazawa et al [48] which demonstrated that vinpo inhibits carrageenan-induced IL-1β and TNF-α production in the paw skin and spinal cord. The anti-inflammatory effect of vinpo can be explained on the basis that it inhibits TNF-α and LPS-induced up-regulation of pro-inflammatory mediators, including TNF-α, IL-1β by targeting ΙκB kinase/NF-κB-dependent pathway via a direct inhibition of the ΙκB kinase complex, thereby suppressing inflammatory responses in-vitro and in-vivo [25].…”

Preconditioning with PDE1 Inhibitors and Moderate-Intensity Training Positively Affect Systemic Redox State of Rats

“…On the other hand, level of O 2 decreased after vinpocetine alone or its combination with training. These results are consistent with an earlier study which showed that vinpocetine in a dose of 30 mg/kg reduced superoxide anion which increased after carrageenan administration [34]. In the same study, it had been shown that neutrophils are cells that are an important source of superoxide anion.…”

Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

“…This is also an analgesic, antioxidant and anti-inflammatory pathway [23,24,49,50]. Nrf2 also induces GSH production [51], therefore, this result is in agreement with the quercetin prevention of GSH depletion.…”