At the University of Minnesota there was an adolescent male patient with congenital insensitivity to pain. I performed a muscle biopsy and sural nerve biopsy on him with no local anesthesia.
A severe diaper rash when she was 2 weeks old didn't faze her. She never fussed when she was hungry, so her parents had to remind themselves to feed her every two hours. At 6 months, she laughed and cooed as a nurse administered stinging drops to dilate her eyes.
Doctors found that Ashlyn had a one-in-a-billion condition: She couldn't feel pain. And unlike most people in medical literature with a documented insensitivity to pain, she was otherwise normal and healthy.
It sounds like a gift. Imagine never having to worry about the discomfort of paper cuts, skinned knees or going to the dentist.
However, being immune to pain is also a curse, both physiologically and philosophically.
You wouldn't know if you were getting too hot or too cold. A sudden medical emergency like a heart attack or appendicitis might go unnoticed until it was too late. And how would you ever feel empathy for the suffering of others if you had never suffered yourself?
Studying Ashlyn in the hope of unlocking the mysteries of pain presents a similar conundrum.
With 30 percent to 40 percent of Americans below the age of 50 suffering from chronic pain, a gene-based cure would improve the quality of millions of lives as well as make its developer very rich. Drugmakers AstraZeneca and Xenon Pharmaceuticals are among those looking for clues in people with an inherited insensitivity to pain.
The researcher who has been studying the Southeast Georgia girl and her family for the past six years admits he is excited about where the field may lead. But Roland Staud also expresses concern about the potential for abuse, citing the temptation for athletes to use a new treatment to perform superhuman feats.
"This is a Pandora's box," said Staud, a rheumatologist and pain expert at the University of Florida College of Medicine in Gainesville.
Her life story, he added, offers "an amazing snapshot of how complicated a life can get without the guidance of pain."
Feeling no pain
By all appearances, Ashlyn is like most any 11-year-old girl.
She wears her maple-brown hair in a single ponytail, runs where she's going, often when walking would be more prudent, and is torn between playing the trumpet or the trombone in the school band. She is the second of three children in a family that lives on the wooded outskirts of Patterson, a town north of Waycross.
Ask her what it's like not to be able to feel pain and she'll simply shrug her shoulders.
It's not that she feels nothing. She can feel pressure, when something's hot or cold, different textures and even burning. But her body's nervous system doesn't relay messages of pain.
That was apparent when she bit a chunk of skin off the side of her hand as a toddler. And when she chewed her bottom lip so much that the swelling hid her top lip. And when she ripped out two front baby teeth trying to remove the cap on a ketchup bottle.
"She can fall down and get up like nothing happened," said her mother, Tara.
But there are exceptions. She has complained at times that her stomach "hurts." That, her parents have learned, is almost always followed immediately by a bathroom episode.
Tara and her husband, John, are extra protective of her.
The living room coffee table was turning into a magnet for injuries, so the family went without one for years. She isn't allowed to join her friends at recess if it's too hot outside. And she has been instructed to tell someone right away if she ever sees blood.
Neither Ashlyn's brother nor her sister share her insensitivity to pain.
Much of what the Blockers do is in unchartered parenting territory. There are no support groups or advice books for families like theirs.
"We decided we would write our book as we go along," Tara said.
Genetic clues
Ashlyn is a researcher's dream. For one thing, she is one of only a few people known in the United States to be impervious to pain. (There are a handful of others around the world, including people in Pakistan, Great Britain and Canada.)
Staud learned about Ashlyn's existence when he was contacted by a TV news reporter for a story about her. Soon, the family was making the 21/2-hour drive to Gainesville once or twice a year so Staud could get to the bottom of what caused her condition.
Last week, Staud and other UF researchers published their findings in the European Journal of Pain.
They found that she had anomalies on a gene known as SCN9A. Other scientists had implicated the gene in pain insensitivity a few years earlier, but the UF researchers found that Ashlyn's condition involved two previously unknown mutations.
They also suspect the mutations are responsible for her inability to detect scents. She has no sense of smell - a realization that eluded her parents until just a year ago, when they conducted an informal "smell test" at home.
Treatments that target how the SCN9A gene functions may hold the key to ending chronic pain for good, Staud said. But he warns against shutting down its rival: acute pain.
Just ask Ashlyn's mother about the pitfalls of that.
"I'd give her my pain mechanism if I could," Blocker said.
jeremy.cox@jacksonville.com, (904) 359-4083
https://www.jacksonville.com/story/news/healthcare/2010/08/29/georgia-girl-who-doesnt-feel-pain-helps-researchers-understand-condition/15932878007/
Abstract
Insensitivity to pain is a rare disorder that is commonly associated with Hereditary Sensory and Autonomic Neuropathies (HSAN I-V) resulting often in autonomic dysfunction and premature death. Very few individuals have been reported with pain insensitivity lacking such autonomic neuropathies. We performed genetic, neurologic, psychological, and psychophysical evaluations in such an individual (OMIM 243000) and her first degree relatives. Sequence analysis of genomic DNA revealed two novel SCN9A mutations in this index case (IC). One was a non-conservative missense mutation (C1719R) in exon 26 present only in the IC and one parent. Further sequence analysis of the child's DNA revealed a 1-bp splice donor deletion in intron 17 which was also present in the other parent and one sibling. Detailed psychophysical testing was used to phenotypically characterize the IC, her family members, and 10 matched normal controls. Similar to family members and controls the IC showed normal somatosensory functioning for non-nociceptive mechanoreception and warmth. However, she demonstrated diminished ability to detect cool temperatures combined with profound deficits in heat and mechanical nociception. Congenital insensitivity to pain in our IC was associated with two novel SCN9A mutations which most likely resulted in a Nav1.7 channelopathy. However, in contrast to individuals with other SCN9A mutations, the observed pain insensitivity was relative and not absolute, which may be consistent with hypomorphic effects of one or both mutations. The ability to sense at least some danger signals may be advantageous and ameliorate the otherwise increased morbidity and mortality of some individuals with congenital insensitivity to pain.
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