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The Journal of Neuroscience, November 1, 2006, 26(44):11287-11294; doi:10.1523/JNEUROSCI.2659-06.2006

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Neurobiology of Disease
Abnormal Function of C-Fibers in Patients with Diabetic Neuropathy

Kristin Ørstavik,^1,2 * Barbara Namer,^3 * Roland Schmidt,⁴ Martin Schmelz,⁵ Marita Hilliges,⁶ Christian Weidner,³ Richard W. Carr,³ Hermann Handwerker,³ Ellen Jørum,² and H. Erik Torebjörk⁴

¹Faculty of Medicine, University of Oslo and ²Laboratory of Clinical Neurophysiology, Department of Neurology, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway, ³Department of Physiology and Experimental Pathophysiology, University of Erlangen/Nürnberg, 91054 Erlangen, Germany, ⁴Department of Clinical Neurophysiology, University Hospital, SE-751 85 Uppsala, Sweden, ⁵Department of Anesthesiology Mannheim, University Heidelberg, D-68135 Mannheim, Germany, and ⁶Department of Sciences, School of Business and Engineering, Halmstad University, SE-301 18 Halmstad, Sweden

Correspondence should be addressed to Dr. Kristin Ørstavik, Department of Neurology, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway. Email: kristin.orstavik{at}medisin.uio.no

The mechanisms underlying the development of painful and nonpainful neuropathy associated with diabetes mellitus are unclear. We have obtained microneurographic recordings from unmyelinated fibers in eight patients with diabetes mellitus, five with painful neuropathy, and three with neuropathy without pain. All eight patients had large-fiber neuropathy, and seven patients had pathological thermal thresholds in their feet, indicating the involvement of small-caliber nerve fibers. A total of 163 C-fibers were recorded at knee level from the common peroneal nerve in the patients (36–67 years old), and these were compared with 77 C-fibers from healthy controls (41–64 years old). The ratio of mechano-responsive to mechano-insensitive nociceptors was 2:1 in the healthy controls, whereas in the patients, it was 1:2. In patients, a fairly large percentage of characterized fibers (12.5% in nonpainful and 18.9% in painful neuropathy) resembled mechano-responsive nociceptors that had lost their mechanical and heat responsiveness. Such fibers were rarely encountered in age-matched controls (3.2%). Afferent fibers with spontaneous activity or mechanical sensitization were found in both patient groups. We conclude that small-fiber neuropathy in diabetes affects receptive properties of nociceptors that leads to an impairment of mechano-responsive nociceptors.

Key words: neuropathy; diabetes; pain; C-fibers; microneurography; degeneration

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Received Feb. 2, 2006; revised Sept. 8, 2006; accepted Sept. 13, 2006.

Correspondence should be addressed to Dr. Kristin Ørstavik, Department of Neurology, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway. Email: kristin.orstavik{at}medisin.uio.no

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