title: Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation.
abstract: The rare nerve growth factor-β (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.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; irene.perini@liu.se.
authors.forename: Irene
authors.initials: I
authors.lastname: Perini
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester, Manchester, United Kingdom; National Institute of Health Research Collaboration for Leadership in Applied Health Research and Care Greater Manchester, Manchester, United Kingdom; University of Exeter Medical School, Exeter, United Kingdom;
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.affiliation: Greater Manchester Neuroscience Centre, Salford Royal Hospital NHS Trust, Salford, United Kingdom; University of Manchester, Manchester, United Kingdom; Liverpool John Moores University, Liverpool, United Kingdom; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Department of Surgery, Unit of Orthopedics, Perioperative Sciences, Umeå University Hospital, Umeå, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Minde
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;
authors.forename: India
authors.initials: I
authors.lastname: Morrison
mesh_terms: D059787:Acute Pain / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D001120:Arginine / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D020932:Nerve Growth Factor / Q000235:genetics*; D010147:Pain Measurement; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000235:genetics; D055815:Young Adult
chemical_list: C502240:NGF protein, human; D014364:Tryptophan; D020932:Nerve Growth Factor; D001120:Arginine
keywords: C-fiber; Situational Pain Questionnaire; corneal confocal microscopy; nerve growth factor-β gene mutation; pain evaluation