Pain

Question 1

dysesthesia

Answer 1

Dysesthesia is a generic term for a cutaneous symptom–such as pruritus, burning, tingling, stinging, anesthesia, hypoesthesia, tickling, crawling, cold sensation, or even pain–without a primary cutaneous condition in a well-defined location that is often caused by nerve trauma, impingement, or irritation.

Question 2

Placement of c-fiber receptors

Answer 2

the epidermis

Question 3

Placement of A-delta-fiber receptors

Answer 3

the dermis

Question 4

Typical representation of Small Fiber neuropathy

Answer 4

Burning feet syndrome

Question 5

Neuropathy

Answer 5

Neuropathy is damage or dysfunction of one or more nerves that typically results in numbness, tingling, muscle weakness and pain in the affected area.

Question 6

morphological

Answer 6

of, relating to, or concerned with form or structure.

Question 7

Corneal confocal microscopy

Answer 7

morphological method to look at the small fiber function. The method allows us to see cornel innervation, which can tell us about skin innervation (non-invasive). Is hoped to be used rather than skin biopsies in the future

Question 8

Microneurography

Answer 8

most precise ways to analyse single fibers using a micro electrode, searching for spontaneous activity

Question 9

mutations for this is mostly associated with small fiber function?

Answer 9

ion-channels

Question 10

Quantitativ sensory testing

Answer 10

Test battery that includes tests to determine the thermal threshold

Question 11

Autonomic test of SNF

Answer 11

quantifying sweating

Question 12

idiopathy

Answer 12

An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin

Question 13

polymorphism

Answer 13

polymorphism is the occurrence of two or more clearly different morphs or forms, also referred to as alternative phenotypes, in the population of a species. … Put simply, polymorphism is when there are two or more possibilities of a trait on a gene.

Question 14

Wild type gene

Answer 14

A non-mutated gene

Question 15

Anosmia

Answer 15

the partial or full loss of smell, might be experienced with Congenital Insensitivity to pain

Question 16

Small Fiber Neuropathy

Answer 16

Subgroup of sensory neuropathies, Pathology: A-delta and C fibers, symptom: burning pain in feet and hands. Fibers might be reduced, and this is examined using Neurological and electrophysiological examination. Electroneurography is normal or slightly abnormal

Question 17

Methods for examining SFN

Answer 17

Quantitativ sensory testing, Autonomic tests, Skin biopsy, Corneal confocal microscopy, pain-related evoked potentials, Microneurography, genetics, histology (stains), electrophysiology (patch clamp), gene expression, cell cultures, animal models

Question 18

Skin biopsy

Answer 18

Used to find possible fiber reduction (morphological)

Question 19

Corneal confocal microscopy

Answer 19

allows us to see cornel innervation, which can tell us about skin innervation (non-invasive, morphological)

Question 20

Microneurography

Answer 20

most precise ways to analyze single fibers using a micro electrode, searching for spontaneous activity

Question 21

features of SFN

Answer 21

Localized, superficial, burning pain and dysesthesias at toes and feet, permanent pain, usually no trigger, Normal neurological and only marginally abnormal electrophysiology, the disorder is usually confined and does not spread.
Patients have an increase in thermal perception hold (cold and warm) - need more stimulus for same effect and there is a decrease in fiber density.

Question 22

Diagnosis of SFN

Answer 22

There is idiopathic cases, and it can be caused by many secondary cases such as diabetes, vitamin B12 deficiency, HIV, etc. Often we see a mutation in the sodium channel genes

Question 23

Erythromelalgia

Answer 23

Hereditary or sporadic forms, Attacks of severe burning pain and red, hot extremities
Unilateral

Question 24

Pathophysiology of Erythromelalgia

Answer 24

Mutations to the NaV1.7 gene, which leads to hyperactivity in the channels and excessive neuronal firing

Question 25

Treatment of Erythromelalgia

Answer 25

Challenging. Symptomatic treatment is cold and rest. Neuropathic pain treatment includes Gabapentine, Causative treatment are sodium channel blockers, but they’re not effective (likely because they’re not specific to NaV1.7)

Question 26

Congenital insensitivity to pain

Answer 26

Genetic pain disorder due to NaV1.7 mutation, no pain is felt, No causative or symptomatic treatment, sometimes correlates with Anosmia and fiber degeneration

Question 27

Which 2 genotypes can lead to the phenotype CIP?

Answer 27

Mutation at NaV1.7 or NaV1.9

Question 28

Mutation in NaV 1.8 can lead to which case example?

Answer 28

The ‘pain everywhere’ example?

Question 29

Hereditary autonomic and sensory neuropathies (HSAN)

Answer 29

Caused by degeneration of sensory neurons and leads to loss of pain sensation. Side effects include dysfunction of Heart rate variability, blood pressure, dyshidrosis, gastrointestinal dysmotility, anosmia, etc.

Question 30

Fabry disease

Answer 30

A Lysosomal storage disorder that is X-chromosome recessive. Seen as a loss of reduction or loss of function of alpha-galactosidase A. Sphingolipid deposits can be found in the neuron. Leads to a disease where every organ is affected to a different degree. Akren pain (from the extremities - hands and feet).
Patients are heat intolerant, experience high intensity pain that is triggerable (fever, hear, activity).
Same genotype, many phenotypes

Question 31

Pain phenotypes in Fabry disease

Answer 31

pain attacks
pain crisis
evoked pain
permanent pain

Question 32

Diagnosis of Fabry disease

Answer 32

alpha-galactosidase A activity

Genetic testing

Question 33

Findings of Fabry disease

Answer 33

Test gives similar results to earlier disorders: increase in thermal detection threshold (particular for cold) –> patients can’t perceive cold stimuli, decreased never fiber density and corneal innervation

Question 34

Treatment of Fabry disease

Answer 34

Enzyme replacement therapy (expensive and ineffective) or Migalastat (oral chaperone, expensive and ineffective)
Symptomatic analgesic treatment can be used if the above-mentioned doesn’t help the pain

Question 35

What can be the reasons behind fiber loss?

Answer 35

Axonopathy (functional or structural defects in the axon or its terminal) or Ganglionopathy (the sensory neuron is ill)

Question 36

Pathophysiology research of Fabry disease

Answer 36

There is more GP3 in sensory neurons, more neurons die, decreased neurite outgrowth, iPSC might be useful to figure out more