• Dagrun Sagafos, Inge P Kleggetveit, Tormod Helås, Roland Schmidt, Jan Minde, Barbara Namer, Martin Schmelz, and Ellen Jørum.
• *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.
• Clin J Pain. 2016 Jul 1; 32 (7): 636-42.

ObjectivesNerve 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).Materials And MethodsOne 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.ResultsLow 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.DiscussionThe 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.

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