Characterization of the role of sensory fibers A (Trkb+) and C fibers (Neurotensin+) in nociceptive and pathological pain

Author(s)

Alexandre Gomes de Macedo Maganin

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2023-03-02

Examining board members

Thiago Mattar Cunha; Soraia Kátia Pereira Costa; Felipe Villela Gomes

• Advisor: Thiago Mattar Cunha

Abstract

Pain is understood as a response generated after the recognition of a noxious stimulus, and may be associated with a real or potential injury. However, inflammatory processes and lesions in the somatosensory system can cause pain to be understood as a pathology. The perception of both nociceptive and pathological pain depends on the recognition of noxious stimuli by nociceptive sensory neurons (egg C fiber), and in cases of pathology (such as neuropathy) also by non-nociceptive sensory neurons (A fibers). However, the classification of these sensory neurons has always been based on morphofunctional characteristics, which has always generated controversy regarding the real function of these neurons in nociception. Because of this, a new classification based on global transcriptional characteristics has been proposed. However, little is known about the real function of the new subgroups and a more precise understanding of the involvement of sensory neurons in the nociceptive transmission pathway may directly contribute to studies of new, more effective therapeutic targets for the treatment of different subtypes of pain. Therefore, the aim of this project is to characterize the involvement of Trkb+ and Neurotensin (Nts)+ sensory nerve fibers in the nociceptive pathway. For this, loss and gain of function approaches will be used with the aid of genetically modified animals that express the enzyme CRE recombinase in these specific populations of sensory neurons. During this study, it was observed that Nts+ fibers do not play a role in nociception, nor in the development of neuropathic pain due to injury and chemotherapy, however apparently Trkb+ fibers, which in naive conditions respond only to innocuous stimuli, in neuropathic conditions it starts to assume a nociceptor role. Furthermore, our data demonstrate the direct involvement of Nts+ fibers in the itch response of animals. (AU)

• FAPESP's process: 19/15063-4 - Characterization of the role of the sensory fibers a (TRKb+) and fibers C (galanin+/neurotensin+) in nociceptive and pathological pain
• Grantee: Alexandre Gomes de Macedo Maganin
• Support Opportunities: Scholarships in Brazil - Doctorate