18 and γ-interferon and Sphingosine-1-phosphate Receptors endothelin-1. It is unclear whether these differences result from different mechanistic device T in the vortex Column or spinal cord mechanisms above. Similar to the model of the vinegar Acid, it is also the involvement of TNF, IL-1 and CXCL1 in the second phase of the formalin test. Nevertheless, there are other important mechanisms in the formalin test such as the activation of dorsal root ganglia of the mitogen activated protein kinase kinase ERK and the activation of PI3K cable. In fact, evidence suggests inhibition of spinal pain management as an effective strategy to reduce pain with reduced incidence of systemic side effects by the Zellaktivit t, kinases and other molecules. In addition to assessing the inhibition of formalin cord of p38 MAP kinases, JNK and ERK and PI3K d Mpfen carrageenan-induced peripheral hyperalgesia, mechanical hyperalgesia induced a cytokine, and nerve injury-induced neuropathic pain. Thus support consistent data that inhibition of the vertebra Column of MAP kinases and PI3K attenuator Tion of inflammatory and neuropathic pain. Therefore, to investigate whether a potential drug has analgesic effects in determining MAP kinase inhibitors vertebra Column and PI3K is an important approach to its mechanisms. In this sense, knowledge of the mechanisms of nociception and nociception in the model definition model involved a crucial phase of a study. Cytokines such as TNF and IL-1 mediation of the writhing reaction induced neuronal activation and cable or the MAP kinases and / or PI3K. It is not known whether vinegar Acid and cause pain PBQ manifest Similar behavior on the activation of p38 cord, ERK and JNK, and / or participation of PI3K or cyclone Column in writhing microglial response. Therefore, the mechanisms in the vortex Pillars Vinegar Acid and the response to M Mice PBQ was on the involvement of MAP kinase, PI3K and microglia written loan Rated most. Two models of the writhing reaction was used to determine whether this reaction to Similar mechanisms of the vertebra Column h Depends despite some mechanistic differences important papers. Furthermore, the model of formalin was used for mechanistic comparison. Second Materials and methods 2.1. The animal experiments were performed on male pattern Swiss-M Performed in mice housed Kunststoffk Provisional clear standard with free access to food and water. All behavioral testing was carried out by 9.00 bis 05.00 clock, checked into room temperature EEA. The procedures for animal care and treatment in accordance with the International Association for the Study of Pain guidelines and with the approval of the Ethics Committee of the Universidade Estadual de Londrina. Were made every effort to minimize the number of animals used and their suffering. It should be noted that different experimenters, the L Made solutions, and administrations that the evaluation manifesto pain behaviors are performed. 2.2. Writhing response tests PBQ and acetic Acid induced wall models were performed as described above, in doses previously determined. PBQ, vinegar Acid or vehicle was in the Bauchfellh choose Of M Mice injected. Each mouse was in a big glass cylinder and the intensity of t the nociceptive behavior was quantified by Z Select the total number of bends, the 0-20 min after injection of the stimulus. The intensity t of writhing responsibility.