Hereditary Sensory and Autonomic Neuropathy type V (HSANV) is a rare genetic disease characterized by a severe reduction in pain perception. Surprisingly, this disease is caused by a specific mutation in the gene coding for Nerve Growth Factor (NGF), a neurotrophin mostly known for its actions on brain development and survival of neurons. Actually, NGF also acts throughout the body as a modulator of the perception of potentially harmful stimuli. To understand how a single mutation can so dramatically impair pain perception, Giovanna Testa and colleagues, working in the of Antonino Cattaneo, have generated and characterized transgenic mice carrying the mutation responsible for HSAN V. These mice have a normal cognitive performance and, overall, normal anatomical structures for transmitting pain to the brain, but perceive potentially harmful stimuli with a decreased intensity. Testa and colleagues also found that the peculiar features of the disease are linked to the decreased ability of mutated “painless” NGF to activate molecular pathways responsible for eliciting pain.
This work provides scientists a new tool to study how such an important sensory modality is originated in the brain, in addition to suggesting new approaches for the treatment of chronic pain.