From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V

Abstract

Hereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder.

Axon Transport and Neuropathy

“…These neuropathies are clearly related to abnormal NGF signaling because they are caused by mutations in TrkA (HSAN4) and NGFb (HSAN5/congenital insensitivity to pain;) genes that alter TrkA-mediated signaling and NGF binding affinity to TrkA, respectively. 85 In other HSAN types, abnormal NGF/TrkA signaling has not been directly investigated, but evidence suggests that abnormalities in this signaling axis may exist. In the AD HSAN1, which is primarily associated with pain and temperature and sometimes with distal motor axon involvement, ras-associated protein 7 (RAB7; OMIM no.…”

Sensory Neuropathy Type V: Dilemma Between Function and Well-being

“…Hereditary sensory and autonomic neuropathy (HSAN) is an extremely rare autosomal recessive pathology first described in 1978 in a 6-year-old Lithuanian girl [4].…”

“…Our patient presents insensitivity to pain, absence of mental retardation and notably self-mutilation of her fingers, lips and tongue. All this clinical manifestations are reported in the literature and found in the rare published cases [1,[4][5][6][7][8]. EMG exploration was in favor of sensitive neuropathy.…”

“…In these patients, the different pathologies progress silently until complications appear [4]. For oral diseases, there is often a silent development of the carious lesions until the establishment of complications such as abscess and cellulitis.…”

“…Unlike HSAN type IV, type V has intact mental abilities and partial anhidrosis. In addition, self-mutilation is an invariable characteristic of the disease, and it often involves lips, fingers, tongue and teeth [1,[4][5][6][7][8].…”