Tropomyosin receptor kinase B-mediated signaling in integration of neuropathic pain and obesity in diabetic polyneuropathy / Sinalização mediada pelo receptor de tropomiosina quinase tipo B na integração de dor neuropática e obesidade na polineuropatia diabética

ABSTRACT

ABSTRACT Objective: To assess the quantitative serum levels of tropomyosin receptor kinase receptor B, and to estimate its association with serum concentration of brain-derived neurotrophic factor and obesity in patients with painful and painless forms of diabetic polyneuropathy. Methods: We examined 70 patients with diabetic polyneuropathy with confirming peripheral nerve dysfunction by electroneuromyography and measuring of serum levels tropomyosin receptor kinase receptor B and brain-derived neurotrophic factor by enzyme immunoassay. Diabetic polyneuropathy was diagnosed using the modified Toronto Consensus (2011) criteria, while neuropathic pain was assessed using an 11-point Numerical Pain Rating Scale. The patients were divided into two groups according to presence or absence of neuropathic pain. Control Group consisted of 14 healthy persons. Results: The serum levels of tropomyosin receptor kinase receptor B and brain-derived neurotrophic factor in patients with diabetic polyneuropathy are significantly higher than healthy controls (p=0.000). Hyperexpression of brain-derived neurotrophic factor in serum was associated with painful form of diabetic polyneuropathy (R=0.392, p=0.012) and obesity (R=0.412, p=0.001). On the contrary high concentration of tropomyosin receptor kinase receptor B in serum associated with painless diabetic polyneuropathy by Pain DETECT (R=-0.354, p=0.015), low body weight (R=-0.354, p=0.015) and severe demyelization of nerve fibers (R=-0.574, p=0.001), indicated "non-working" receptor detected in serum. Conclusion: Tropomyosin receptor kinase receptor B signaling is involved in the modulation of neuropathic pain and obesity in diabetic polyneuropathy.

RESUMO

RESUMO Objetivo: Avaliar os níveis séricos quantitativos do receptor da tropomiosina quinase B, e estimar sua associação com os níveis séricos do fator neurotrófico derivado do cérebro e a obesidade, em pacientes com formas dolorosas e indolores de polineuropatia. Métodos: Examinamos 70 pacientes com polineuropatia diabética, com disfunção de nervo periférico confirmada por eletroneuromiografia e medida de níveis séricos do receptor da tropomiosina quinase B e do fator neurotrófico derivado do cérebro, por imunoensaio enzimático. Polineuropatia diabética foi diagnosticada através dos critérios modificados do Consenso de Toronto (2011), e a dor neuropática foi avaliada pela escala Numerical Pain Rating com 11 pontos. Os pacientes foram divididos em dois grupos, conforme presença ou ausência de dor neuropática. O Grupo Controle tinha 14 indivíduos saudáveis. Resultados: Os níveis séricos do receptor da tropomiosina quinase B e do fator neurotrófico derivado do cérebro em pacientes com polineuropatia diabética são significativamente mais elevados do que controles saudáveis (p=0,000). Hiperexpresssão do fator neurotrófico derivado do cérebro no soro foi associada à forma dolorosa da polineuropatia diabética (R=0,392, p=0,012) e obesidade (R=0,412, p=0,001). Por outro lado, alta concentração sérica de receptor da tropomiosina quinase B, associada à polineuropatia diabética indolor por PainDETECT (R=-0,354, p=0,015), baixo peso corporal (R=-0,354, p=0,015) e grave desmielização de fibras nervosas (R=-0,574, p=0,001), indicaram receptor "não funcionante" detectado no soro. Conclusão: A sinalização do receptor da tropomiosina quinase B está envolvida na modulação da dor neuropática e obesidade na polineuropatia diabética.