IP: Dr. Juan Carlos Arévalo Martín

Resumen del proyecto: During development neurotrophins modulate survival and differentiation of nervous system whereas in adulthood they regulate the correct functioning of the nervous system. Nerve growth factor (NGF), the first discovered neurotrophin, mediates its functions through binding to the receptor tyrosine kinase TrkA. NGF/TrkA-mediated signalling plays a seminal role in the sensibility to pain as knock-out mice for TrkA and NGF present a large reduction of sensory neurons and they are insensitive to thermal pain. Moreover, mutations in TrkA that inactivate the activity of the receptor are responsible for Congenital Insensitivity to Pain with Anhidrosis (CIPA), a hereditary autosomal recessive disorder characterized by, among other symptoms, the absence of reaction to noxious stimuli. In response to NGF TrkA is activated and its functions are modulated by Nedd4-2-mediated ubiquitination. Recently, it has been deposited in the NCBI repository an SNP (rs145023447) that corresponds to a change of C to T in the first base of a codon coding for Proline782 that will become Serine782. This substitution makes TrkA insensitive to Nedd4-2 ubiquitination. Our laboratory has generated a knock-in mouse in which Proline782 has been mutated to Serine782. This knock-in mouse is hypersensitive to thermal and inflammatory acute noxious stimuli. Therefore, our aim is to investigate whether there is any correlation between the presence of SNP (rs145023447) and the development of increase sensitivity to pain in fibromyalgia patients.

Entidad financiadora: Ministerio de Ciencia e Innovación