The effect of neurotrophic factors on morphology, TRPV1 expression and capsaicin responses of cultured human DRG sensory neurons

• Published in: Neuroscience letters 2006-05, Vol.399 (1), p.51-56
• Main Authors: Anand, U., Otto, W.R., Casula, M.A., Day, N.C., Davis, J.B., Bountra, C., Birch, R., Anand, P.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Capsaicin - pharmacology; Capsaicin response; Cell Size; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Human DRG; Humans; Male; NAV1.8 Voltage-Gated Sodium Channel; Nerve Growth Factor - metabolism; Nerve Growth Factors - metabolism; Neurons; Neurons, Afferent - cytology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Neurotrophic factors; Neurotrophin 3 - metabolism; Pain; Potassium Channels, Calcium-Activated - biosynthesis; Sodium Channels - biosynthesis; TRPV Cation Channels - biosynthesis; TRPV1; Vanilloid receptor; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.01.046

We have studied the effect of key neurotrophic factors (NTFs) on morphology, levels of the vanilloid receptor-1 (TRPV1) and responses to capsaicin in adult human sensory neurons in vitro. Avulsed dorsal root ganglia (DRG, n = 5) were cultured with or without a combination of nerve growth factor (NGF), glial cell (line)-derived growth factor (GDNF) and neurotrophin3 (NT3) for 5 days. In the absence of NTFs, the diameter of neurons ranged from 20 to 100 μm (mean 42 ± 4 μm). Adding NTFs caused a significant increase in neuronal sizes, up to 120 μm (mean diameter 62 ± 5 μm, P < 0.01, t-test), an overall 35% increase of TRPV1-positive neurons ( P < 0.003), and notably of large TRPV1-positive neurons >80 μm ( P < 0.05). Responses to capsaicin were significantly enhanced with calcium ratiometry ( P < 0.0001). Short duration (1 h) exposure of dissociated sensory neurons to NTFs increased numbers of TRPV1-positive neurons, but not of TRPV3, Nav 1.8 and IK1 and the morphological size-distribution remained similar to intact post-mortem DRG neurons. NTFs thus increase size, elevate TRPV1 levels and enhance capsaicin responses in cultured human DRG neurons; these changes may relate to pathophysiology in disease states, and provide an in vitro model to study novel analgesics.