Participation of nitric oxide synthase and tumor necrosis factor alpha in chronic pain model

• Grant number: 08/10456-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2009
• End date: December 31, 2009
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marucia Chacur
• Grantee: Aline Carolina Giardini
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The peripheral nerve injury results in persistent and/or chronic pain, characterized by spontaneous pain followed by alodinia and hyperalgesia. The occurrence of pathological changes in the peripheral nervous system and spinal cord contribute to the development of neuropathic pain. These changes include rapid and intense discharges in the injured peripheral nerve fibers, which keep the afferent nerve impulses to the central nervous system. Several substances synthesized and/or released during the inflammatory process, such as cininas, neuropeptides, cytokines, nitric oxide, can interfere with the activity of sensory afferent nerve fibers. In spinal cord, peripheral nerve injury causes the release of pro-inflammatory cytokines by glial cells, such as interleukin-1 beta and tumor necrosis factor-alpha (TNFa), which mediate the nociceptive processes from this injury. It is important to identify which factors are released in the neuropathic pain model for a better understanding of the mechanisms involved in this phenomenon. Thus, the aim of the project is to assess the participation of TNFa and nitric oxide synthase in a chronic pain model induced by chronic constriction injury of sciatic nerve in rats. We will determine the distribution of TNFa and the neuronal nitric oxide (nNOS) by immunohistochemistry assay. Still, the painful sensitivity will be evaluated in animals using anti-TNFa and an inhibitor of nNOS. We hope that this series of investigations help in elucidation the mechanisms involved in the genesis of neuropathic pain. Moreover, the identification of different mediators could provide information for a better development of different clinical treatments. (AU)