Daniel Barbier

Life Without Pain

The child's parents first realized something was wrong when their 4-month-old developed severe teething sores, and two months later those first teeth fell out. The boy frequently bled from his mouth and lost more teeth when gnawing on toys. Then he bit off part of his tongue, with nary a whimper. He had other symptoms: minor wounds that wouldn't heal, ulcerations between his fingers, and he didn't scream when receiving injections. When X-rays revealed a previously undetected skull fracture, doctors diagnosed a hereditary sensory and autonomic neuropathy (HSAN).¹

The boy had HSAN4, or congenital insensitivity to pain. Two mutations in the neurotrophic tyrosine kinase receptor type I (NTRK1) gene left his skin lacking nociceptors. The five HSANs, which vary by severity, age of onset, and mutated gene, vividly demonstrate that pain is vital. "People with inability to feel pain rarely make it past age 25. They become blind by rubbing their eyes, their teeth rot, and they break bones and suffer from burns," says Jeffrey A. Katz, associate director of the section for pain medicine at Northwestern University's Feinberg School of Medicine in Chicago.

The original description of HSAN2 concerned a large family in Newfoundland whose many affected members had such numbness in their extremities that their digits detached. HSAN3 is even worse; because it impairs autonomic functions, individuals cannot control body temperature or blood pressure. They can't cry.

HSAN1 strikes at an average age of 25, with distal loss of pain and thermal sensitivity, ulcers, and in some families, deafness, explains Monica Holmberg, a professor in the department of medical biosciences at Umeå University in Sweden. The HSAN1 mutation is in the serine palmitoyltransferase 1 gene. Her group investigates HSAN5 in a large family in northern Sweden in whom the nerve growth factor b gene is mutated.² "The severely affected patients have an early age of onset and suffer from multiple fractures and joint problems," she adds.

The HSANs are exceedingly rare. A much more common form of pain insensitivity is a complication of diabetes mellitus, in which lack of sensation leads to ulcerated sores. Studies in mice and biopsies from patients implicate too many receptors for NF-kB activation, somehow triggered by the complex chemical milieu that is a response to hyperglycemia.³