Differential impairment of the sudomotor and nociceptor axon-reflex in diabetic peripheral neuropathy
It is not known whether C‐fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C‐fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C‐fiber functio...
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| Vydané v: | Muscle & nerve Ročník 33; číslo 4; s. 494 - 499 |
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| Abstract | It is not known whether C‐fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C‐fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C‐fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C‐fiber (axon‐reflex)–mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C‐fiber–mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C‐fiber–mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon‐reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C‐fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus. Muscle Nerve, 2006 |
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| AbstractList | It is not known whether C-fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C-fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C-fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C-fiber-mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C-fiber-mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon-reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C-fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus. Muscle Nerve, 2006 It is not known whether C-fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C-fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C-fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C-fiber-mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C-fiber-mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon-reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C-fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus.It is not known whether C-fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C-fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C-fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C-fiber-mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C-fiber-mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon-reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C-fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus. It is not known whether C‐fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C‐fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C‐fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C‐fiber (axon‐reflex)–mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C‐fiber–mediated flare response was reduced in type 2 diabetic patients ( P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C‐fiber–mediated responses, including sweat volume ( P < 0.05) and the number of activated sweat glands ( P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon‐reflex sweat area in patients with type 1 diabetes ( P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C‐fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus. Muscle Nerve, 2006 It is not known whether C-fiber functional subclasses are differentially affected by diabetes mellitus or whether the patterns of C-fiber dysfunction are different between type 1 and type 2 diabetes. We therefore examined efferent sympathetic sudomotor and primary afferent nociceptor C-fiber function in diabetic patients. Acetylcholine (10%) was used to evoke C-fiber (axon-reflex)-mediated responses. The nociceptor (flare) response was measured using a laser Doppler device. The sudomotor response was quantified with silastic imprints. The nociceptor C-fiber-mediated flare response was reduced in type 2 diabetic patients (P < 0.008) but was similar to controls in type 1 diabetic patients. The sympathetic C-fiber-mediated responses, including sweat volume (P < 0.05) and the number of activated sweat glands (P = 0.003), were increased in patients with type 1 diabetes. There also was a trend toward a larger axon-reflex sweat area in patients with type 1 diabetes (P = 0.09). No differences in these sweat responses were found in patients with type 2 diabetes compared to controls. These findings suggest that the functional abnormalities in diabetic peripheral neuropathy are not homogeneous and that C-fiber subclasses are differentially affected in type 1 and 2 diabetes mellitus. |
| Author | Kilo, Sonja Hilz, Max J. Freeman, Roy Berghoff, Martin |
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| Cites_doi | 10.1093/brain/123.10.2118 10.2337/diabetes.50.2.436 10.1111/j.1600-0404.1995.tb06999.x 10.1002/mus.880110613 10.1212/WNL.34.6.758 10.1152/japplphysiol.01167.2000 10.1212/WNL.50.2.480 10.1093/jnen/62.3.260 10.1007/BF00315014 10.1056/NEJM198805193182005 10.1212/WNL.59.6.917 10.1002/mus.880090502 10.1002/ana.410150514 10.1002/ana.410140513 10.1016/S0025-6196(12)65338-5 10.1212/WNL.54.6.1246 10.1093/brain/awh175 10.1002/ana.410290604 10.1002/mus.880171205 10.1212/01.WNL.0000040250.31755.F9 10.1136/jnnp.49.9.1059 10.2337/diab.39.8.898 |
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| Keywords | Endocrinopathy Type 2 diabetes Human Immunopathology axon-reflex Nervous system diseases c-fiber dysautonomia Autoimmune disease Metabolic diseases Peripheral neuropathy Axon reflex laser Doppler flowmetry Nociceptor Type 1 diabetes Dysfunction autonomic function Peripheral nerve disease Sweat diabetes silastic imprint method |
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| References | Pierson CR, Zhang W, Murakawa Y, Sima AA. Insulin deficiency rather than hyperglycemia accounts for impaired neurotrophic responses and nerve fiber regeneration in type 1 diabetic neuropathy. J Neuropathol Exp Neurol 2003; 62: 260-271. Kilo S, Berghoff M, Hilz M, Freeman R. Neural and endothelial control of the microcirculation in diabetic peripheral neuropathy. Neurology 2000; 54: 1246-1252. Britland ST, Young RJ, Sharma AK, Clarke BF. Association of painful and painless diabetic polyneuropathy with different patterns of nerve fiber degeneration and regeneration. Diabetes 1990; 39: 898-908. Theriault M, Dort J, Sutherland G, Zochodne DW. A prospective quantitative study of sensory deficits after whole sural nerve biopsies in diabetic and nondiabetic patients. Surgical approach and the role of collateral sprouting. Neurology 1998; 50: 480-484. Bradley JL, Thomas PK, King RH, Muddle JR, Ward JD, Tesfaye S, et al. Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy: correlation with type of diabetes. Acta Neuropathol (Berl) 1995; 90: 403-410. Fealey RD, Low PA, Thomas JE. Thermoregulatory sweating abnormalities in diabetes mellitus. Mayo Clin Proc 1989; 64: 617-628. Polydefkis M, Hauer P, Sheth S, Sirdofsky M, Griffin JW, McArthur JC. The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 2004; 127: 1606-1615. Berghoff M, Kathpal M, Kilo S, Hilz MJ, Freeman R. Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation. J Appl Physiol 2002; 92: 780-788. Parkhouse N, Le Quesne PM. Impaired neurogenic vascular response in patients with diabetes and neuropathic foot lesions. N Engl J Med 1988; 318: 1306-1309. Kennedy WR, Navarro X, Kamei H. Reinnervation of sweat glands in the mouse: axonal regeneration versus collateral sprouting. Muscle Nerve 1988; 11: 603-609. Ahmed ME, Le Quesne PM. Quantitative sweat test in diabetics with neuropathic foot lesions. J Neurol Neurosurg Psychiatry 1986; 49: 1059-1062. Caselli A, Rich J, Hanane T, Uccioli L, Veves A. Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes. Neurology 2003; 60: 297-300. Low PA, Caskey PE, Tuck RR, Fealey RD, Dyck PJ. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol 1983; 14: 573-580. Benarroch EE, Low PA. The acetylcholine-induced flare response in evaluation of small fiber dysfunction. Ann Neurol 1991; 29: 590-595. Kennedy WR, Sakuta M, Sutherland D, Goetz FC. The sweating deficiency in diabetes mellitus: Methods of quantitative and clinical correlation. Neurology 1984; 34: 758-763. Hoeldtke RD, Bryner KD, Horvath GG, Phares RW, Broy LF, Hobbs GR. Redistribution of sudomotor responses is an early sign of sympathetic dysfunction in type 1 diabetes. Diabetes 2001; 50: 436-443. Kennedy JM, Zochodne DW. The regenerative deficit of peripheral nerves in experimental diabetes: its extent, timing and possible mechanisms. Brain 2000; 123: 2118-2129. Bickel A, Kramer HH, Hilz MJ, Birklein F, Neundorfer B, Schmelz M. Assessment of the neurogenic flare reaction in small-fiber neuropathies. Neurology 2002; 59: 917-919. Longo FM, Powell HC, Lebeau J, Gerrero MR, Heckman H, Myers RR. Delayed nerve regeneration in streptozotocin diabetic rats. Muscle Nerve 1986; 9: 385-393. Kennedy WR, Sakuta M, Sutherland D, Goetz FC. Quantitation of the sweating deficiency in diabetes mellitus. Ann Neurol 1984; 15: 482-488. Lang E, Spitzer A, Claus D, Neundorfer B, Handwerker HO. Stimulation of sudomotor axon reflex mechanism by carbachol in healthy subjects and patients suffering from diabetic polyneuropathy. Acta Neurol Scand 1995; 91: 251-254. Stewart JD, Nguyen DM, Abrahamowicz M. Quantitative sweat testing using acetylcholine for direct and axon reflex mediated stimulation with silicone mold recording; controls versus neuropathic diabetics. Muscle Nerve 1994; 17: 1370-1377. 1991; 29 2002; 59 2001; 50 2004; 127 1989; 64 1995; 91 1995; 90 1984; 15 1990; 39 1986; 9 2000; 54 1984; 34 1986; 49 1988; 11 2002; 92 1998; 50 2000; 123 1994; 17 2003; 60 1988; 318 2003; 62 1983; 14 e_1_2_7_5_2 e_1_2_7_4_2 e_1_2_7_3_2 e_1_2_7_2_2 e_1_2_7_9_2 e_1_2_7_8_2 e_1_2_7_7_2 e_1_2_7_6_2 e_1_2_7_19_2 e_1_2_7_18_2 e_1_2_7_17_2 e_1_2_7_16_2 e_1_2_7_15_2 e_1_2_7_14_2 e_1_2_7_13_2 e_1_2_7_12_2 e_1_2_7_23_2 e_1_2_7_11_2 e_1_2_7_22_2 e_1_2_7_10_2 e_1_2_7_21_2 e_1_2_7_20_2 |
| References_xml | – reference: Kennedy JM, Zochodne DW. The regenerative deficit of peripheral nerves in experimental diabetes: its extent, timing and possible mechanisms. Brain 2000; 123: 2118-2129. – reference: Berghoff M, Kathpal M, Kilo S, Hilz MJ, Freeman R. Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation. J Appl Physiol 2002; 92: 780-788. – reference: Pierson CR, Zhang W, Murakawa Y, Sima AA. Insulin deficiency rather than hyperglycemia accounts for impaired neurotrophic responses and nerve fiber regeneration in type 1 diabetic neuropathy. J Neuropathol Exp Neurol 2003; 62: 260-271. – reference: Kennedy WR, Sakuta M, Sutherland D, Goetz FC. The sweating deficiency in diabetes mellitus: Methods of quantitative and clinical correlation. Neurology 1984; 34: 758-763. – reference: Bickel A, Kramer HH, Hilz MJ, Birklein F, Neundorfer B, Schmelz M. Assessment of the neurogenic flare reaction in small-fiber neuropathies. Neurology 2002; 59: 917-919. – reference: Bradley JL, Thomas PK, King RH, Muddle JR, Ward JD, Tesfaye S, et al. Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy: correlation with type of diabetes. Acta Neuropathol (Berl) 1995; 90: 403-410. – reference: Britland ST, Young RJ, Sharma AK, Clarke BF. Association of painful and painless diabetic polyneuropathy with different patterns of nerve fiber degeneration and regeneration. Diabetes 1990; 39: 898-908. – reference: Kilo S, Berghoff M, Hilz M, Freeman R. Neural and endothelial control of the microcirculation in diabetic peripheral neuropathy. Neurology 2000; 54: 1246-1252. – reference: Caselli A, Rich J, Hanane T, Uccioli L, Veves A. Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes. Neurology 2003; 60: 297-300. – reference: Fealey RD, Low PA, Thomas JE. Thermoregulatory sweating abnormalities in diabetes mellitus. Mayo Clin Proc 1989; 64: 617-628. – reference: Stewart JD, Nguyen DM, Abrahamowicz M. Quantitative sweat testing using acetylcholine for direct and axon reflex mediated stimulation with silicone mold recording; controls versus neuropathic diabetics. Muscle Nerve 1994; 17: 1370-1377. – reference: Hoeldtke RD, Bryner KD, Horvath GG, Phares RW, Broy LF, Hobbs GR. Redistribution of sudomotor responses is an early sign of sympathetic dysfunction in type 1 diabetes. Diabetes 2001; 50: 436-443. – reference: Benarroch EE, Low PA. The acetylcholine-induced flare response in evaluation of small fiber dysfunction. Ann Neurol 1991; 29: 590-595. – reference: Polydefkis M, Hauer P, Sheth S, Sirdofsky M, Griffin JW, McArthur JC. The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 2004; 127: 1606-1615. – reference: Ahmed ME, Le Quesne PM. Quantitative sweat test in diabetics with neuropathic foot lesions. J Neurol Neurosurg Psychiatry 1986; 49: 1059-1062. – reference: Kennedy WR, Navarro X, Kamei H. Reinnervation of sweat glands in the mouse: axonal regeneration versus collateral sprouting. Muscle Nerve 1988; 11: 603-609. – reference: Lang E, Spitzer A, Claus D, Neundorfer B, Handwerker HO. Stimulation of sudomotor axon reflex mechanism by carbachol in healthy subjects and patients suffering from diabetic polyneuropathy. Acta Neurol Scand 1995; 91: 251-254. – reference: Low PA, Caskey PE, Tuck RR, Fealey RD, Dyck PJ. Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol 1983; 14: 573-580. – reference: Parkhouse N, Le Quesne PM. Impaired neurogenic vascular response in patients with diabetes and neuropathic foot lesions. N Engl J Med 1988; 318: 1306-1309. – reference: Theriault M, Dort J, Sutherland G, Zochodne DW. A prospective quantitative study of sensory deficits after whole sural nerve biopsies in diabetic and nondiabetic patients. Surgical approach and the role of collateral sprouting. Neurology 1998; 50: 480-484. – reference: Kennedy WR, Sakuta M, Sutherland D, Goetz FC. Quantitation of the sweating deficiency in diabetes mellitus. Ann Neurol 1984; 15: 482-488. – reference: Longo FM, Powell HC, Lebeau J, Gerrero MR, Heckman H, Myers RR. Delayed nerve regeneration in streptozotocin diabetic rats. 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| SubjectTerms | Acetylcholine - pharmacology Adult autonomic function axon-reflex Axons - physiology Biological and medical sciences c-fiber Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction Data Interpretation, Statistical diabetes Diabetes Mellitus, Type 1 - physiopathology Diabetes Mellitus, Type 2 - physiopathology Diabetic Nephropathies - physiopathology dysautonomia Female Forearm - innervation Forearm - physiology Humans Iontophoresis laser Doppler flowmetry Male Medical sciences Middle Aged Nerve Fibers, Unmyelinated - physiology Nervous system (semeiology, syndromes) Neurology Nociceptors - physiology Reflex - physiology Regional Blood Flow - physiology silastic imprint method Skin - blood supply Skin - innervation Sweating - physiology Sympathetic Nervous System - physiology Vasodilation - physiology Vasodilator Agents - pharmacology |
| Title | Differential impairment of the sudomotor and nociceptor axon-reflex in diabetic peripheral neuropathy |
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