Single-Fiber Recordings of Nociceptive Fibers in Patients With HSAN Type V With Congenital Insensitivity to Pain.
Nerve growth factor (NGF) is a protein important for growth and survival, but also for modulation of sensitivity of nociceptors and sympathetic neurons. The purpose of the present study was to investigate the effects of reduced NGF signaling in patients with hereditary sensory and autonomic neuropathies type V, congenital insensitivity to pain, caused by a mutation of the NGFβ gene, including a characterization of single nociceptive fibers using microneurography (MNG).



One homozygote and 2 heterozygote patients with this mutation were examined with electromyography/neurography, thermal testing, quantitative sudomotor axon reflex test, and electrically induced axon reflex erythema in addition to MNG.



Low quantitative sudomotor axon reflex test measurements of 0.02 (left foot) and 0.03 (right foot) μL/cm and elevated thermal thresholds for warmth and cold detection testing showed clear impairment of small nerve fibers, both sudomotor efferent and somatic afferent fibers, in the patient homozygote for the mutation. MNG from one of the heterozygote patients revealed changes in the small nociceptive fibers in skin, including abnormally low conduction velocity, spontaneous activity in A-δ fibers and C-nociceptors and abnormal or lacking response to heat.



The findings of grossly intact pain thresholds compared with anamnestic insensitivity of pain in deep somatic tissue such as bone suggest a gradient of impairment dependent on different NGF availability in various tissues. Even though these patients in some aspects report insensitivity to pain, they also report chronic spontaneous pain as their main symptom, strikingly highlighting differential mechanisms of insensitivity to evoked pain versus spontaneous pain.
*Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway †Department of Clinical Neurophysiology, Uppsala University, Uppsala ‡Department of Surgery, Unit of Orthopedics, Perioperative Sciences, Umeå University Hospital, Umeå, Sweden §Department of Physiology and Experimental Pathophysiology, University of Erlangen, Erlangen ∥Department of Anaesthesiology and Operative Intensive Care, Heidelberg University, Mannheim, Germany.
Dagrun
D
Sagafos
Inge P
IP
Kleggetveit
Tormod
T
Helås
Roland
R
Schmidt
Jan
J
Minde
Barbara
B
Namer
Martin
M
Schmelz
Ellen
E
Jørum
D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000503:physiopathology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020932:Nerve Growth Factor / Q000235:genetics*; D009619:Nociceptors / Q000502:physiology*; D000699:Pain Insensitivity, Congenital / Q000235:genetics* / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology; D012018:Reflex / Q000235:genetics / Q000502:physiology
C502240:NGF protein, human; D020932:Nerve Growth Factor