Chronic pain conditions, such as neuropathic pain, are a common problem that poses a major challenge to health-care providers due to its complex natural history, unclear aetiology and poor response towards therapy. Despite the large number of drugs available, the adherence is limited by the large range of side effects and pharmacological ineffectiveness. Thus, the search for new chemical entities that can act as promising molecules to treat chronic pain conditions has emerged. The natural products remain as the most promising sources of new chemical entities with applicability for the medical approach. Hence, we performed a systematic review analysing pre-clinical studies shown to be promising in a possible applicability in neuropathic pain. The search terms neuropathic pain, phytotherapy and medicinal plants were used to retrieve English language articles in LILACS, PUBMED and EMBASE published until 10 April 2013. From a total of 1529 articles surveyed, 28 met the inclusion and exclusion criteria established. The main chemical compounds studied were flavonoids (28%), terpenes (17%), alkaloids (14%), phenols (10%), carotenoids (10%) and others (21%). The mostly described animal models for the study of neuropathic pain included were chronic constriction injury (CCI -32%), partial sciatic nerve ligation (PSNL -28%), streptozotocin -induced diabetic (28%), alcoholic neuropathy (3.5%), sodium monoiodoacetate (MIA -3.5%) and neuropathic pain induced by paclitaxel (3.5%). The opioids, serotonergic and cannabinoid systems are suggested as the most promising targets for the natural products described. Therefore, the data reviewed here suggest that these compounds are possible candidates for the treatment of chronic painful conditions, such as neuropathic pain.
Inflammatory response can be driven by cytokine production and is a pivotal target in the management of inflammatory diseases. Monoterpenes have shown that promising profile as agents which reduce the inflammatory process and also modulate the key chemical mediators of inflammation, such as pro and anti-inflammatory cytokines. The main interest focused on monoterpenes were to develop the analgesic and anti-inflammatory drugs. In this review, we summarized current knowledge on monoterpenes that produce anti-inflammatory effects by modulating the release of cytokines, as well as suggesting that which monoterpenoid molecules may be most effective in the treatment of inflammatory disease. Several different inflammatory markers were evaluated as a target of monoterpenes. The proinflammatory and antiinflammatory cytokines were found TNF-α, IL-1β, IL-2, IL-5, IL-4, IL-6, IL-8, IL-10, IL-12 IL-13, IL-17A, IFNγ, TGF-β1 and IFN-γ. Our review found evidence that NF-κB and MAPK signaling are important pathways for the anti-inflammatory action of monoterpenes. We found 24 monoterpenes that modulate the production of cytokines, which appears to be the major pharmacological mechanism these compounds possess in relation to the attenuation of inflammatory response. Despite the compelling evidence supporting the anti-inflammatory effect of monoterpenes, further studies are necessary to fully explore their potential as anti-inflammatory compounds.
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