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Effect of the trans-caryophyllene in the hypernociception induced by chronic constriction of sciatic nerve and potentiated by stress of the sleep restriction

Grant number: 13/02787-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2016
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Deborah Suchecki
Grantee:Lyvia Izaura Gomes de Paula Freire
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The bidirectional relationship between sleep and pain has been topic of interest in many recent investigations, since patients with pain-associated pathologies are bad sleepers and people who sleep poorly have higher pain sensitivity. Moreover, both painful stimuli and poor sleep are known to activate brain regions that regulate stress response and are closely related to the affective/emotional pain dimension. It has been shown that animals with peripheral nerve injury, under sleep deprivation or restriction, have reduced pain threshold. However, conventional treatments for neuropathic pain do not reverse the increased sensitivity to pain and may cause several undesirable effects. Thus, studies using natural products have contributed significantly to the development of new therapeutic strategies. Considering that trans-caryophyllene is the major active principle in the essential oil of many medicinal plants with pronounced antinociceptive activity, such as Cannabis sativa, the aim of this study is to assess its effect on the hypernociception induced by chronic constriction injury (CCI) and potentiated by stress and sleep restriction (SR) in mice. For this purpose, C57BL/6J mice, treated with trans-caryophyllene or vehicle, will undergo chronic constriction of the sciatic nerve and, after 6 days of recovery, they will be sleep restricted for 15 days. To determine the potential anti-hypernociceptive, the mice will be periodically evaluated for mechanical (von Frey test) and thermal (hot plate test) hypernociception. Finally, we will evaluate the effects of trans-caryophyllene on corticosterone levels, Fos and Egr-1 expression in regions involved in response to pain, stress and sleep, and the expression of pro-inflammatory (TNF , PGE2, IL-1² and IL-6) and immunomodulatory (IL-10) and the expression of cyclooxygenase 2 (COX2). (AU)