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MicroRNA 16 expression in dorsal root ganglion and spinal cord dorsal column of mice submitted to peripheral neuropathy

Grant number: 05/03821-9
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2006
Effective date (End): October 31, 2008
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Guilherme de Araújo Lucas
Grantee:Ricardo Kusuda
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Neuropathic pain is an intractable, chronic syndrome that may arise from injury to peripheral nerves and is associated with allodynia, hyperalgesia, spontaneous pain, repetitive discharge of nociceptors and the expansion of receptive fields of nociceptive input. Our understanding of the pathophysiology of this debilitating syndrome is very limited and represents the main obstacle to the development of more effective therapeutic strategies. Recently, in vitro studies indicated that TrkB neurotrophin receptor strongly modulate cannabinoid activity, suggesting a communication between two different classes of receptors. In the present study, we will explore the functional consequences of this interaction in an animal model of neuropathic pain. The main objectives of the project are:1) to investigate TrkB modulation of CB1 induced CREB phosphorylation in the spinal cord dorsal horn following chronic peripheral nerve injury. 2) study nerve lesion-induced CREB phosphorylation in the spinal cord dorsal horn of mice with reduced TrkB activity (TrkB.T1);This proposal combines unique genetic tools, cellular methods with pharmacological and behavioral paradigms to uncover the contribution of neurotrophic factors in the action of cannabinoid activity. We will pursue multidisciplinary studies aiming at delineating new, fundamental neurobiological mechanisms underlying chronic pain. Most important, this project may reveal novel mechanistically based targets for development of more effective and specific analgesic drugs.