Study of ATP release mediated by Panx1 and exocytosis on dorsal root ganglion: effect on nociception and hyperalgesia

Author(s)

Julia Borges Paes Lemes

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2021-08-20

Examining board members

Carlos Amílcar Parada; Amanda Ferreira Neves; Cássia Regina da Silva; Gisele Picolo; Luana Fischer

• Advisor: Carlos Amílcar Parada

Abstract

The ATP (adenosine triphosphate), primarily known as an intracellular energy source, play an important role as a signaling molecule on the extracellular environment under various physiological and pathological processes that occur in the Nervous System. In recent years, ATP has stood out in the transmission of nociception by interacting with the membrane channels of nociceptors, reducing the activation threshold, and modifying neuronal excitability. Although there are no synapses in the sensory ganglia, the dorsal root ganglion (DRG) is an important site for pain modulation. Studies showed that ATP is the main mediator of communication between neurons and glia in DRG. Our research group has highlighted the importance of that communication in processes involving acute pain and inflammatory pain transmission. The ATP molecule can be released to extracellular space through membrane channels and/or by vesicle exocytosis. The membrane channel called Panexin1 (Panx1) seems to have a more relevant role in the nervous system regarding the release of ATP and for painful signal transmission. Despite this, there are still few studies on ATP-mediated signaling in DRG, which prevents a deeper understanding of the peripheral mechanisms involved in pain modulation. Thus, the present work aimed to understand the release of ATP through the Panx1 channels and by exocytosis of vesicles in the dorsal root ganglion. Also, to study the effect of this release on the development of inflammatory and neuropathic hyperalgesia, as well as the acute C-fiber nociception. Behavioral pain experiments were performed using pharmacological inhibitors for Panx1 channels and exocytosis directly in the dorsal root ganglion (L5) of rats... The complete abstract is available with the full electronic document (AU)

• FAPESP's process: 17/19105-8 - Study of the release of ATP in the dorsal root ganglion in the development of inflammatory hyperalgesia
• Grantee: Júlia Borges Paes Lemes
• Support Opportunities: Scholarships in Brazil - Doctorate