Membrane properties in small cutaneous nerve fibers in humans
Kristian Hennings PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorKen Steffen Frahm PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorLaura Petrini PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorOle K. Andersen PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorLars Arendt-Nielsen PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorCorresponding Author
Carsten D. Mørch PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Correspondence to: C. D. Mørch; e-mail: [email protected]Search for more papers by this authorKristian Hennings PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorKen Steffen Frahm PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorLaura Petrini PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorOle K. Andersen PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorLars Arendt-Nielsen PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Search for more papers by this authorCorresponding Author
Carsten D. Mørch PhD
Integrative Neuroscience Group, SMI, Department of Health Science and Technology, Aalborg University, Frederik Bajers Vej 7, Aalborg, Denmark
Correspondence to: C. D. Mørch; e-mail: [email protected]Search for more papers by this authorABSTRACT
Introduction: Assessment of membrane properties is important for understanding the mechanisms of painful peripheral neuropathy, developing new diagnostic techniques, and screening/profiling of analgesics that target ion channels. Methods: Small cutaneous nerves were activated electrically by small diameter (0.2 mm) cathodes, and large nerves were activated by ordinary patch electrodes. This new perception threshold tracking method combines perception threshold assessment and stimulation paradigms from conventional threshold tracking. Results: The strength-duration time-constant of large fibers (580 µs ± 160 µs) was lower than the time constant of small fibers (1060 µs ± 690 µs; P < 0.01, paired t-test). Threshold electrotonus showed similar threshold reductions to sub-threshold prepulses, except for 80 ms hyperpolarizing prepulses, to which small fibers showed less threshold reduction than large fibers (repeated-measures analysis of variance, Bonferroni, P = 0.006). Conclusions: This is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. Muscle Nerve 55: 195–201, 2017
REFERENCES
- 1Moldovan M, Alvarez S, Romer Rosberg M, Krarup C. Axonal voltage-gated ion channels as pharmacological targets for pain. Eur J Pharmacol 2013; 708: 105–112.
- 2Z'Graggen WJ, Bostock H. Nerve membrane excitability testing. Eur J Anaesthesiol Suppl (EJA) 2008; 42; 68–72.
- 3Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve 1998; 21: 137–158.
10.1002/(SICI)1097-4598(199802)21:2<137::AID-MUS1>3.0.CO;2-C CAS PubMed Web of Science® Google Scholar
- 4Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol 2001; 112: 1575–1585.
- 5Kiernan MC, Burke D, Andersen KV, Bostock H. Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve 2000; 23: 399–409.
10.1002/(SICI)1097-4598(200003)23:3<399::AID-MUS12>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- 6Bostock H, Baker M. Evidence for two types of potassium channel in human motor axons in vivo. Brain Res 1988; 462: 354–358.
- 7Horn S, Quasthoff S, Grafe P, Bostock H, Renner R, Schrank B. Abnormal axonal inward rectification in diabetic neuropathy. Muscle Nerve 1996; 19: 1268–1275.
- 8McHugh JC, Tryfonopoulos D, Fennelly D, Crown J, Connolly S. Electroclinical biomarkers of early peripheral neurotoxicity from oxaliplatin. Eur Cancer Care 2012; 21: 782–789.
- 9Park SB, Lin CSY, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede development of neuropathy. Brain 2009; 132: 2712–2723.
- 10Haanpää M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira D, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain 2011; 152: 14–27.
- 11Lauria G, Merkies ISJ, Faber CG. Small fibre neuropathy. Curr Opin Neurol 2012; 25: 542–549.
- 12Brismar T, Sima AAF, Greene DA. Reversible and irreversible nodal dysfunction in diabetic neuropathy. Ann Neurol 1987; 21: 504–507.
- 13Mørch CD, Hennings K, Andersen OK. Estimating nerve excitation thresholds to cutaneous electrical stimulation by finite element modeling combined with a stochastic branching nerve fiber model. Med Biol Eng Comput 2011; 49: 385–395.
- 14Lelic D, Mørch CD, Hennings K, Andersen OK, Drewes AM. Differences in perception and brain activation following stimulation by large versus small area cutaneous surface electrodes. Eur J Pain 2012; 16: 827–837.
- 15Gracely RH. Studies of pain in normal man. In: R Melzack, PD Wall, editors. Textbook of pain. London: Churchill Livingstone; 1994. p 315–336.
- 16Weiss G. Sur la possibility de rendre comparables entre eux les appareils servant à l 'excitation électrique. Arch Ital Biol 1901; 35: 413–446.
- 17Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull 1979; 86: 420–428.
- 18Weir JP. Quantifying test-retest reliability using the intraclass correlation coefficient and the SEM. J Strength Cond Res 2005; 19: 231–240.
- 19Atkinson G, Nevill AM. Statistical methods for assessing measurement error (reliability) in variables relevant to sports medicine. Sports Med 1998; 26: 217–238.
- 20Bromm B, Meier W. The intracutaneous stimulus - a new pain model for algesimetric studies. Methods Find Exp Clin Pharmacol 1984; 6: 405–410.
- 21Inui K, Tran TD, Hoshiyama M, Kakigi R. Preferential stimulation of A-delta fibers by intra-epidermal needle electrode in humans. Pain 2002; 96: 247–252.
- 22Mouraux A, Iannetti GD, Plaghki L. Low intensity intra-epidermal electrical stimulation can activate Ad-nociceptors selectively. Pain 2010; 150: 199–207.
- 23Frahm KS, Mørch CD, Grill WM, Lubock NB, Hennings K, Andersen OK. Activation of peripheral nerve fibers by electrical stimulation in the sole of the foot. BMC Neurosci 2013; 14: 116.
- 24Hilliges M, Wang LX, Johansson O. Ultrastructural evidence for nerve-fibers within all vital layers of the human epidermis. J Invest Dermatol 1995; 104: 134–137.
- 25Perchet C, Frot M, Charmarty A, Flores C, Mazza S, Magnin M, et al. Do we activate specifically somatosensory thin fibres with the concentric planar electrode? A scalp and intracranial EEG study. Pain 2012; 153: 1244–1252.
- 26Otsuru N, Inui K, Yamashiro K, Miyazaki T, Takeshima Y, Kakigi R. Assessing ad fiber function with lidocaine using intraepidermal electrical stimulation. J Pain 2010; 11: 621–627.
- 27Motogi J, Kodaira M, Muragaki Y, Inui K, Kakigi R. Cortical responses to C-fiber stimulation by intra-epidermal electrical stimulation: an MEG study. Neurosci Lett 2014; 570: 69–74.
- 28Mogyoros I, Kiernan MC, Burke D. Strength-duration properties of human peripheral nerve. Brain 1996; 119: 439–447.
- 29Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. Sodium channels in normal and pathological pain. Annu Rev Neurosci 2010; 33: 325–347.
- 30Baker M, Bostock H, Grafe P, Martius P. Function and distribution of three types of rectifying channel in rat spinal root myelinated axons. J Physiol 1987; 383: 45–67.
- 31Strian F, Lautenbacher S, Galfe G, Hölzl R. Diurnal variations in pain perception and thermal sensitivity. Pain 1989; 36: 125–131.
- 32Procacci P, Buzzelli G, Passeri I, Sassi R, Voegelin MR, Zoppi M. Studies on the cutaneous pricking pain threshold in man. Circadian and circatrigintan changes. Res Clin Stud Headeache 1970; 3: 260–276.
- 33Nielsen CS, Stubhaug A, Price DD, Vassend O, Czajkowski N, Harris JR. Individual differences in pain sensitivity: genetic and environmental contributions. Pain 2008; 136: 21–29.
- 34Chung SC, Um BY, Kim HS. Evaluation of pressure pain threshold in head and neck muscles by electronic algometer: intrarater and interrater reliability. Cranio 1992; 10: 28–34.
- 35Rosier EM, Iadarola MJ, Coghill RC. Reproducibility of pain measurement and pain perception. Pain 2002; 98: 205–216.
- 36Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science 2000; 288: 1769–1772.
- 37Nielsen CS, Staud R, Price DD. Individual differences in pain sensitivity: measurement, causation, and consequences. J Pain 2009; 10: 231–237.