Twenty-one cases in which pain, pleasure, sleep and memory behave differently from what we expect.
21 cases/12 min main reading/Optional notes and sources
The comparison
One gene, different kinds of pain
Some changes to the SCN9A gene cause attacks of burning pain. Other changes leave a person unable to feel pain from birth.
SCN9A encodes Nav1.7, a sodium channel involved in nerve signals. Certain variants make pain-sensing neurons more excitable; other variants prevent the channel from working. The effects depend on the particular mutation and how it is inherited. The diagram below compares distinct mutations, not stages that a person moves between. SCN9A GeneReviewsCox 2006
That comparison is a useful beginning. These conditions can separate things we normally experience together: recognizing a face and feeling it is familiar, moving a hand and feeling responsible for it, remembering a life and learning a new list. Some mechanisms are well established. Others rest on a few patients and competing explanations. The difference matters throughout this guide.
Distinct changes to SCN9A
Two effects of altered Nav1.7 channels, with different inheritance patterns.
This compares mutation-specific effects. Erythromelalgia also has causes unrelated to SCN9A, and several other genes can cause congenital pain insensitivity. SCN9A GeneReviewsPain insensitivity GeneReviews
One
Pain that persists
Complex regional pain syndrome
Pain after an injury
After an injury, a limb can develop continuing pain out of proportion to the original damage, with changes in temperature, color, swelling or movement. Touch that should be harmless may hurt. CRPS involves altered pain processing alongside other nervous-system and inflammatory changes. A clinic study of 39 patients found an association between suicidal thoughts, pain and depressive symptoms. It cannot establish a suicide rate for everyone with CRPS. Lee 2014
Cluster headache
Severe attacks around one eye
Cluster headache produces recurring attacks of intense one-sided pain, often with a watering eye, a blocked nose and restless movement. In an online survey of 1,604 people meeting the study's cluster-headache criteria, the average recalled pain rating was 9.7 out of 10. The survey's case definition already required severe pain. Its rating describes respondents' experience, rather than an objective ranking of all pain: participation was voluntary, diagnoses were not independently confirmed, and other conditions were rated from memory. High-flow oxygen is an established treatment for attacks. Burish 2021Oxygen trial, 2009
Inherited erythromelalgia
Burning, hot, red extremities
Feet or hands become red and warm during attacks of burning pain, often triggered by heat or exercise. Some inherited cases come from gain-of-function SCN9A variants that make pain-sensing neurons easier to excite. Severity varies, even within a family, and the pain need not be constant. This is the first half of the gene comparison above. It explains one form of erythromelalgia, not every person with the condition. GeneReviews
Two
Pleasure and appetite
Ecstatic seizures
Bliss as a seizure symptom
A small number of people with focal epilepsy describe brief feelings of intense well-being, clarity or certainty during a seizure. In one clinical case published in 2013, electrical stimulation of the right anterior insula reproduced the patient's ecstatic sensation. That supports a role for this region in a wider seizure network. The reports are too few to establish a universal explanation for ecstatic experiences. Picard 2013Clinical review
Gourmand syndrome
A new preoccupation with good food
After a stroke, a political journalist became absorbed in dining and eventually changed from political reporting to food columns. His doctors used this and another case to investigate newly acquired eating interests. Their 1997 study identified 36 patients with gourmand syndrome; 34 had damage involving the right anterior brain, across several regions and causes. Many also had cognitive or behavioral difficulties. The eating interest was one part of a broader change. The series connects it with brain injury without showing that a particular lesion will produce it. Regard and Landis 1997
Musical chills
Frisson
A passage of music can bring a shiver, goosebumps and intense pleasure. In a small imaging experiment, eight listeners selected for reliable musical chills showed PET changes consistent with dopamine release while hearing their chosen music. A separate fMRI analysis distinguished activity before the chills from activity at their peak. The study connects musical pleasure with reward processing, while separating the buildup from the peak. Its carefully selected listeners do not represent everyone who enjoys music. Salimpoor 2011
Optional: pressing for pleasure
Classic brain-stimulation experiments made animals repeatedly work for stimulation. Some human patients also pressed stimulation buttons compulsively. But repeated pressing measures reinforcement: a strong drive to obtain something need not mean extraordinary enjoyment of it. Reviews distinguish wanting from liking, and question whether the famous human experiments demonstrated pure pleasure. Kringelbach and Berridge 2010
Three
When control breaks down
Fatal familial insomnia
An inherited prion disease
Despite the name, this is more than an inability to sleep. A disease-associated PRNP variant causes a fatal neurodegenerative illness involving abnormal prion protein, with severe sleep disruption, autonomic problems and progressive movement and cognitive changes. Damage is especially prominent in the thalamus. The course varies, and sleep medicines do not cure the underlying disease. Clinical overview
Fear after amygdala damage
The patient known as SM
SM, a woman with bilateral amygdala damage from Urbach-Wiethe disease, reported little fear while handling snakes, visiting a haunted house or watching frightening films. Yet she and two other patients with similar damage experienced panic during a laboratory carbon-dioxide inhalation challenge. Their results complicate the idea that the amygdala is the single source of fear. Its damage can affect responses to external threats without abolishing fear arising from an internal bodily threat. Feinstein 2011Feinstein 2013
Lesch-Nyhan disease
Compulsive self-injury with pain intact
The severe form of an HPRT1-related disorder disrupts the recycling of purines, components of DNA and RNA. It causes excess uric acid and serious neurological difficulties, including involuntary movement and compulsive self-injury, most often in boys. A child may bite his lips or fingers while still feeling pain. This is not evidence that he wants to be hurt. Protective equipment, careful care and treatment of the broader disorder matter; punishment can make the behavior worse. HPRT1 GeneReviewsClinical overview
Four
Sleep and waking overlap
REM sleep behavior disorder
Moving during dreams
During REM sleep, most skeletal muscles normally lose their tone. In RBD, this suppression is impaired, and people may shout, punch or act out dreams. Isolated RBD can precede a neurodegenerative disease. A specialist cohort of 1,280 patients produced an estimated 73.5 percent risk of developing parkinsonism or dementia by 12 years. This was a survival-analysis estimate, not a count showing that three quarters of all participants became ill: average follow-up was 3.6 years. The group was older and mostly male. Its result describes that diagnosed cohort, not every cause of dream movement or an individual's future. Postuma 2019
Cataplexy
Muscle weakness while awake
Laughter or another strong emotion can bring sudden weakness: a jaw droops, knees buckle, or the whole body collapses. Consciousness is usually preserved, and attacks can last seconds to minutes. Cataplexy is closely associated with narcolepsy type 1 and the loss of neurons that produce orexin, a chemical involved in stabilizing wakefulness. The overlap with REM muscle suppression helps explain the symptom, though an attack is not simply the person falling asleep. Dauvilliers 2014
Sleep paralysis
Aware but unable to move
Someone waking up or falling asleep can become aware while REM-associated muscle paralysis persists. They may be unable to move or speak, with frightening perceptions of an intruder, pressure on the chest or floating outside the body. Similar experiences recur in accounts from different cultures, though hallucinations do not accompany every episode. The overlap of waking awareness and sleep physiology explains much of the experience without determining how a person interprets it. Sharpless and Barber 2011
Optional: long sleep and sudden bangs
Kleine-Levin syndrome causes recurring episodes of prolonged sleep, with changes such as confusion and altered behavior during an episode. People often return toward their usual function between episodes, although some have lasting difficulties. Miglis and Guilleminault 2014 Exploding head syndrome is different: a person perceives a sudden loud noise around a sleep transition, generally without pain. Clinical overview
Five
Recognition, belief and agency
Cotard delusion
Believing you are dead
A person may believe they are dead, do not exist, or have lost their organs. One man with severe depression believed his brain had died while his body remained alive. A 2013 PET case study found reduced metabolism across parts of his frontal and parietal cortex compared with healthy controls. His EEG was normal, and he was awake and speaking. This was not a brain-death finding or a comparison with anesthesia. Depression, medication and the lack of a matched patient group limit what this single scan can explain about Cotard delusion. Charland-Verville 2013
Capgras delusion
A familiar person seems an impostor
Someone believes a loved one has been replaced by an identical impostor. In a 1997 case study, a man with a head injury recognized his parents' photographs but lacked the usual difference in skin-conductance response between familiar and unfamiliar faces. He accepted his parents' identity over the telephone. The authors proposed disrupted links between visual recognition and emotional familiarity, alongside problems evaluating the resulting belief. It is a plausible explanation for that patient's pattern, not proof of a severed wire in every case. Hirstein and Ramachandran 1997
Alien hand syndrome
Movement without a sense of control
A hand may grasp objects or interfere with what the other hand is doing, without the person intending the action. Sometimes the hand also feels unfamiliar or unowned. Different forms occur after damage to frontal, parietal or callosal regions, including after stroke. These cases help distinguish making a movement from experiencing agency over it. The different injury patterns also show why no single broken connection explains every case. Panikkath 2014
Optional: visions after sight loss
Charles Bonnet syndrome involves visual hallucinations in people with impaired vision. They may see figures, animals or patterned scenes, often while recognizing that the images are not real. Its reported frequency varies across populations and diagnostic definitions. Clinical overview
Six
The body remade
Bone where it should not grow
Fibrodysplasia ossificans progressiva
FOP causes extra bone to form in soft connective tissues, including muscles, tendons and ligaments. It can bridge joints and restrict movement. Disease-associated ACVR1 variants alter bone-forming signals; episodes can occur spontaneously or after injury. Unnecessary biopsies, operations and intramuscular injections can provoke further bone formation, so care must account for that risk. Characteristic malformed great toes are often present at birth, before extra bone develops. GeneReviews
Blue skin from altered hemoglobin
Hereditary methemoglobinemia
A Kentucky family helped make inherited methemoglobinemia famous. In one form, variants in both copies of CYB5R3 reduce an enzyme's ability to restore oxidized hemoglobin. The resulting methemoglobin cannot carry oxygen normally and can make skin appear blue. The type confined mainly to red blood cells differs from a more severe form affecting other tissues. Methylene blue can lower methemoglobin in suitable patients; it does not repair the inherited defect and can be dangerous with G6PD deficiency. Cawein 1964Expert recommendations, 2021
Progeria
Hutchinson-Gilford progeria syndrome
The classic form comes from a particular LMNA variant that produces progerin, an abnormal form of a protein supporting the cell nucleus. Children develop growth failure, loss of body fat and hair, joint stiffness and serious cardiovascular disease. Intellectual development is usually normal. Some features resemble aging, but the condition is not a complete accelerated version of ordinary life: its pattern of disease is specific, and it does not reproduce every illness of old age. GeneReviews
Optional: Julia Pastrana
Pastrana, a singer and dancer with hypertrichosis and enlarged gums, was exhibited for her appearance. After her death in 1860, her husband and manager had her body embalmed and continued displaying it. In 2012, a Norwegian research-ethics committee recommended return and burial of her remains, while acknowledging that her own wishes were unknown. Her story belongs here as a history of how a person was treated, rather than as another unusual body to inspect. Committee statement
Seven
Unusual abilities and their limits
Congenital insensitivity to pain
SCN9A loss of function
Loss-of-function variants in both copies of SCN9A can prevent pain sensation from birth. Touch and other abilities may remain intact, but loss of smell is characteristic. Without pain's warning, unnoticed burns, injuries and joint damage become serious hazards. Other genes cause different forms of congenital pain insensitivity, sometimes with additional impairments. The original 2006 report identified SCN9A mutations in affected people from three Pakistani families. Cox 2006GeneReviews
These genetic findings made Nav1.7 a target for pain research. A recent drug milestone concerns another channel. Suzetrigine, sold as Journavx and approved in the US in 2025 for moderate to severe acute pain in adults, selectively blocks Nav1.8. It is not an approved SCN9A/Nav1.7 drug. FDA label
Highly superior autobiographical memory
Remembering dates and personal events
People with HSAM can retrieve unusually detailed memories tied to dates in their own lives. In a 2012 study of 11 selected participants, they named the weekday for randomly chosen past dates correctly about 97 percent of the time, compared with about 15 percent for controls. They also recalled personal events, with some checked against records. Performance on many standard laboratory memory tasks was ordinary. The ability is specific, and neither that study nor its results establish perfect recall of every day, every detail or every kind of information. LePort 2012
Human echolocation
Learning to interpret echoes
Some blind people use tongue clicks and their echoes to judge objects and navigate. In a 2011 experiment with two expert echolocators, recorded echoes activated parts of the brain usually associated with vision. The small study showed how these experts processed echoes, rather than how every blind person would. A later study trained 12 blind and 14 sighted adults over 20 sessions in ten weeks. Both groups improved on echolocation tasks. The ability can be learned, with practice and improvement measured in specific tasks. Thaler 2011Norman 2021
Optional: a reported scent of Parkinson's
Joy Milne's reported ability to recognize an odor associated with Parkinson's helped motivate a study of skin sebum. The researchers found candidate chemical markers that differed between their patient and control samples. These are candidate markers requiring validation, rather than a clinical screening test. Her report of noticing an odor before diagnosis was retrospective. Trivedi 2019
What the cases show
Abilities can come apart
Rare conditions can expose distinctions that everyday experience conceals. But a memorable patient, a mutation's effect in a cell and a long-term cohort answer different questions. A case can suggest a mechanism. Establishing how widely it applies takes further evidence.
Further reading
Sources and kinds of evidence
Sources include original studies, clinical references and official documents. Case reports describe particular people; experiments test narrower questions; cohort estimates depend on who was enrolled and followed. Clinical reviews put those findings in context.
Thumbnail and cover image: "Male skeleton with a rhinoceros" from Bernhard Siegfried Albinus and Jan Wandelaar, Tabulae sceleti et musculorum corporis humani (1747). Public domain, via the Wellcome Collection.
