Journal
JOURNAL OF NEUROPHYSIOLOGY
Volume 116, Issue 2, Pages 425-430Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00667.2015
Keywords
nerve growth factor-beta gene mutation; corneal confocal microscopy; pain evaluation; Situational Pain Questionnaire; C-fiber
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Funding
- Swedish Research Council Distinguished Young Investigator Award [FF-2013-687]
- National Institute for Health Research Wellcome Trust Clinical Research Facility
- Heidelberg Engineering UK
- Heidelberg Engineering Sweden
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The rare nerve growth factor-beta (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience.
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