Abstract
Purpose
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, autosomal recessive disorder characterized by lack of pain and thermal sensation, anhidrosis, thermodysregulation, and mental retardation. Although nonnociceptive sensation, which is mediated by large-caliber myelinated Aβ fibers, is reported to be normal in CIPA patients, precise clinical assessments of this type of sensation have yet to be performed. The aim of this study was to evaluate peripheral sensory nerve function, including senses of touch/pressure, vibration, joint position, and two-point discrimination, in patients with CIPA by basic clinical neurological examination.
Methods
We examined touch/pressure sense, deep senses (vibration, joint proprioception), and two-point discrimination in 12 patients with CIPA (six males and six females aged 11–44) and 12 age- and sex-matched healthy controls. Touch/pressure sense was examined with Semmes–Weinstein monofilaments, vibration sense with a tuning fork, and two-point discrimination with a vernier caliper. Joint proprioception was assessed through subject recognition of passive movement of the great toe.
Results
Perception thresholds of touch/pressure, vibration, and two-point discrimination were significantly higher (p < 0.05), and proprioception sensitivity was significantly lower (p < 0.05) in CIPA patients than in the healthy controls.
Conclusions
Our findings suggest that CIPA patients suffer from more widespread disturbances of sensation than has been previously recognized. Impairment may not be restricted to the types of sensation conducted by peripheral sensory Aδ and C fibers.
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References
Dearborn GV (1932) A case of congenital pure analgesia. J Nerv Ment Dis 75:612–615
Daniel A, Shekim WO, Koresko RL, Dekirmenjian H (1980) Congenital sensory neuropathy with anhidrosis—a case report and investigation of autonomic nervous system abnormalities. J Dev Behav Pediatr 1:49–53
Rosemberg S, Marie SK, Kliemann S (1994) Congenital insensitivity to pain with anhidrosis (hereditary sensory and autonomic neuropathy type IV). Pediatr Neurol 11:50–56
Jarade EF, El-Sheikh HF, Tabbara KF (2002) Indolent corneal ulcers in a patient with congenital corneal ulcers in a patient with anhidrosis: a case report and literature review. Eur J Ophthalmol 12:60–65
Dyck PJ, Mellinger JF, Reagan TJ et al (1983) Not ‘indifference to pain’ but varieties of hereditary sensory and autonomic neuropathy. Brain 106:373–390
Indo Y, Tsuruta M, Hayashida Y et al (1996) Mutations in the TRAK/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat Genet 13:485–488
Miranda M, Di Virgilio M, Selleri S et al (2002) Novel pathogenic mechanisms of congenital insensitivity to pain with anhidrosis genetic disorder unveiled by functional analysis of neurotrophic tyrosine receptor kinase type1/nerve growth factor receptor mutations. J Biol Chem 277:6455–6462
Nolano M, Crisci C, Santoro L, Barbieri F et al (2000) Absent innervations of skin and sweat glands in congenital insensitivity to pain with anhidrosis. Clin Neurophisiol 111:1596–1601
Hasegawa Y, Ninomiya M, Yamada Y, Hattori T (1990) Osteoarthropathy in congenital sensory neuropathy with anhidrosis. Clin Orthop Relat Res 258:232–236
Okuno T, Inoue A, Izumo S (1990) Congenital insensitivity to pain with anhidrosis, a case report. J Bone Joint Surg Am 72:279–282
Goebel HH, Veit S, Dyck PJ (1980) Confirmation of virtual unmyelinated fiber absence in hereditary neuropathy type IV. J Neuropathol Exp Neurol 39:670–675
Swanson AG, Buchan GC, Alvord EC Jr (1965) Anatomic changes in congenital insensitivity to pain. Absence of small primary sensory neurons in ganglia, roots, and Lissauer’s tract. Arch Neurol 12:12–18
Swanson AG, Buchan GC (1963) Absence of Lissauer’s tract and small dorsal root axons in familial, congenital, universal insensitivity to pain. Trans Am Neurol Assoc 88:99–103
Shorer Z, Moses SW, Hershkovitz E, Pinsk V, Levy J (2001) Neurophysiologic studies in congenital insensitivity to pain with anhidrosis. Pediatr Neurol 25:397–400
Indo Y (2000) Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV: clinical, biological and molecular aspects of mutations in TRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor. Clin Auton Res 12(Suppl I):20–32
Maricich SM, Wellnitz SA, Nelson AM et al (2009) Merkel cells are essential for light-touch responses. Science 324:1580–1582
van Nes SI, Faber CG, Hamers RMTP et al (2008) Revising two-point discrimination assessment in normal aging and in patients with polyneuropathies. J Neurol Neurosurg Psychiatry 79:832–834
Acknowledgments
The authors are grateful for the help and support of the CIPA patient members of the “Tomorrow” association, Mr. Noritaka Kawashima of the National Rehabilitation Center for Persons with Disabilities, and Mr. Masanari Noguchi for their assistance in planning and conducting this study. This work was supported in part by a Grant-for-Research on Intractable Diseases from the Ministry of Health, Labour, and Welfare of Japan.
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Iijima, M., Haga, N. Evaluation of nonnociceptive sensation in patients with congenital insensitivity to pain with anhidrosis. Childs Nerv Syst 26, 1085–1089 (2010). https://doi.org/10.1007/s00381-009-1057-6
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DOI: https://doi.org/10.1007/s00381-009-1057-6