{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T07:46:13Z","timestamp":1777189573826,"version":"3.51.4"},"reference-count":67,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:p> Diabetic neuropathy is a common complication of diabetes mellitus patients. It is a wide range of abnormalities affecting proximal and distal peripheral sensory and motor nerves. Although plasma hyperosmolality is a common finding in diabetes mellitus, the effects of hyperosmolality on conduction of various sensory signal components have not been addressed in detail. Here we show that in rat dorsal root ganglion (DRG) preparations from normal rats, hyperosmolar solutions (360 mmol\/kg, containing increased glucose, sucrose, NaCl, or mannitol) produce a selective block of signal propagation in myelinated sensory A-fibers. In compound action potential (CAP) recordings with suction electrodes, peak A-fiber CAP amplitude was selectively decreased (20%), while the C-fiber peak remained intact or was slightly increased. Hyperosmolar solutions had smaller effects on conduction velocity (CV) of both A- and C-fibers (approximately 5% decrease). Hyperosmolality-induced CAP changes could not be observed during recordings from isolated spinal nerves but were evident during recordings from desheathed spinal nerves. In intracellular recordings, hyperosmolar solutions produced a block of spinal nerve-evoked action potential invasion into the somata of some A-fiber neurons. Removal of extracellular calcium completely prevented the hyperosmolality-induced CAP decreases. Based on these data, we propose that the decreased CAP amplitudes recorded in human patients and in animal models of diabetes are in part due to the effects of hyperosmolality and would depend on the extracellular osmolality at the time of sensory testing. We also hypothesize that hyperosmolality may contribute to both the sensory abnormalities (paresthesias) and the chronic pain symptoms of diabetic neuropathy. <\/jats:p>","DOI":"10.1152\/jn.00689.2003","type":"journal-article","created":{"date-parts":[[2004,1,31]],"date-time":"2004-01-31T00:58:22Z","timestamp":1075510702000},"page":"48-56","source":"Crossref","is-referenced-by-count":28,"title":["Hyperosmolar Solutions Selectively Block Action Potentials in Rat Myelinated Sensory Fibers: Implications for Diabetic Neuropathy"],"prefix":"10.1152","volume":"91","author":[{"given":"Yoshizo","family":"Matsuka","sequence":"first","affiliation":[{"name":"Division of Oral Biology and Medicine, UCLA School of Dentistry, University of California, Los Angeles, California 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Spigelman","sequence":"additional","affiliation":[{"name":"Division of Oral Biology and Medicine, UCLA School of Dentistry, University of California, Los Angeles, California 90095"},{"name":"Brain Research Institute, University of California, Los Angeles, California 90095"},{"name":"Dental Research Institute, University of California, Los Angeles, California 90095"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)00008-X"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-197203000-00001"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.1999.00028.x"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-23-10277.2002"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.8.2.125"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1973.tb05414.x"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(83)80023-7"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1993.tb00026.x"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1981.tb06928.x"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210515"},{"key":"REF11","unstructured":"Celiker R, Basgoze O, and Bayraktar M. Early detection of neurological involvement in diabetes mellitus. Electromyogr Clin Neurophysiol 36: 29\u201335, 1996."},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1016\/1056-8727(95)00084-4"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(76)90299-5"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90435-5"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03828-3"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(01)00410-1"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.11.10.876"},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.10.1637"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019583"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1976.sp011345"},{"key":"REF21","doi-asserted-by":"crossref","unstructured":"Fulop M, Tannenbaum H, and Dreyer N. Ketotic hyperosmolar coma. Lancet 2: 635\u2013639, 1973.","DOI":"10.1016\/S0140-6736(73)92478-1"},{"key":"REF22","unstructured":"Gamble HJ. Comparative electron-microscopic observations on the connective tissues of a peripheral nerve and a spinal root in the rat. J Anat 98: 17\u201325, 1964."},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.2337\/diab.20.4.228"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.25.1.11"},{"key":"REF25","doi-asserted-by":"crossref","unstructured":"Greene DA, Yagihashi S, Lattimer SA, and Sima AAF. Nerve Na+-K+-ATPase, conduction, and myoinositol in the insulin-deficient BB rat. Am J Physiol 247: E534\u2013E539, 1984.","DOI":"10.1152\/ajpendo.1984.247.4.E534"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015573"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015574"},{"key":"REF28","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.51.2.221"},{"key":"REF29","unstructured":"Hille B. The superfamily of voltage-gated channels. In: Ion Channels of Excitable Membranes, edited by Hille B. Sunderland: Sinauer, 2001, p. 61\u201393."},{"key":"REF30","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8727(98)00019-1"},{"key":"REF31","doi-asserted-by":"crossref","unstructured":"Horowitz SH. Diabetic neuropathy. Clin Orthop 78\u201385, 1993.","DOI":"10.1097\/00003086-199311000-00015"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1007\/BF00401840"},{"key":"REF33","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(96)01366-6"},{"key":"REF34","unstructured":"Imam I, Salako BL, and Akinola A. Peripheral neuropathy in Nigerian subjects with chronic renal failure. Niger J Med 12: 72\u201375, 2003."},{"key":"REF35","unstructured":"Junge D. Voltage clamping. In: Nerve and Muscle Excitation, edited by Junge D. Sunderland: Sinauer, 1992, p. 78\u201396."},{"key":"REF36","unstructured":"Koester J. Passive membrane properties of the neuron. In: Principles of Neural Science, edited by Kandel ER, Schwartz JH, and Jessel TM. New York: Elsevier, 1991a, p. 94\u2013103."},{"key":"REF37","unstructured":"Koester J. Voltage-gated ion channels and the generation of the action potential. In: Principles of Neural Science, edited by Kandel ER, Schwartz JH, and Jessel TM. New York: Elsevier, 1991b, p. 104\u2013118."},{"key":"REF38","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(81)90088-9"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019068"},{"key":"REF40","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1983.141"},{"key":"REF41","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.9.1558"},{"key":"REF42","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(76)85673-1"},{"key":"REF43","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(80)90156-2"},{"key":"REF44","doi-asserted-by":"crossref","unstructured":"Mulder DW, Lambert EH, Bastron JA, and Sprague RG. The neuropathies associated with diabetes mellitus. Neurology 11: 275\u2013284, 1961.","DOI":"10.1097\/00132985-196104000-00001"},{"key":"REF45","unstructured":"Muravitskaia OS, Nevenglovskii IE, Smirnova VA, and Rumiantsev VB. The osmolarity of the blood and urine in patients with tuberculosis of the urinary system and chronic kidney failure. Urol Nefrol (Mosk) 1: 19\u201322, 1990."},{"key":"REF46","doi-asserted-by":"crossref","unstructured":"Murphy M and Carmichael AJ. Renal itch. Clin Exp Dermatol 25: 103\u2013106, 2000.","DOI":"10.1046\/j.1365-2230.2000.00587.x"},{"key":"REF47","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/117.1.185"},{"key":"REF48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.135bf.x"},{"key":"REF49","doi-asserted-by":"publisher","DOI":"10.1038\/247284a0"},{"key":"REF50","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199507133330203"},{"key":"REF51","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199910)22:10<1403::AID-MUS10>3.0.CO;2-Z"},{"key":"REF52","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199810)21:10<1246::AID-MUS2>3.0.CO;2-B"},{"key":"REF53","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.165"},{"key":"REF54","doi-asserted-by":"publisher","DOI":"10.1126\/science.154.3755.1464"},{"key":"REF55","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(74)90136-1"},{"key":"REF56","doi-asserted-by":"publisher","DOI":"10.1007\/BF01262054"},{"key":"REF57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-08-05068.1994"},{"key":"REF58","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.4.1733"},{"key":"REF59","unstructured":"Spigelman I, Gold MS, and Light AR. Electrophysiological recording techniques in pain research. In: Methods in Pain Research, edited by Kruger L. Boca Raton: CRC, 2001, p. 147\u2013168."},{"key":"REF60","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.11.1932"},{"key":"REF61","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91154-S"},{"key":"REF62","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.3.1924"},{"key":"REF63","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051477"},{"key":"REF64","doi-asserted-by":"publisher","DOI":"10.1007\/BF02598216"},{"key":"REF65","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(89)90218-2"},{"key":"REF66","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2000.00298.x"},{"key":"REF67","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1993.tb00208.x"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00689.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T04:51:35Z","timestamp":1568004695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00689.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,1]]}},"alternative-id":["10.1152\/jn.00689.2003"],"URL":"https:\/\/doi.org\/10.1152\/jn.00689.2003","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1]]}}}