title: Thalamic amplification of sensory input in experimental diabetes.
abstract: Diabetic neuropathy is a common, and often debilitating, secondary complication of diabetes mellitus. As pain, hypersensitivity and paraesthesias present in a distal-proximal distribution, symptoms are generally believed to originate from damaged afferents within the peripheral nervous system. Increasing evidence suggests altered processing within the central nervous system in diabetic neuropathy contributes towards somatosensory dysfunction, but whether the accurate coding and relay of peripherally encoded information through the central nervous system is altered in diabetes is not understood. Here, we applied the strengths of the rodent whisker-barrel system to study primary afferent-thalamic processing in diabetic neuropathy. We found that neurons in the thalamic ventral posteromedial nucleus from rats with experimental diabetic neuropathy showed increased firing to precisely graded, multidirectional whisker deflection compared to non-diabetic rats. This thalamic hyperactivity occurred without any overt primary afferent dysfunction, as recordings from the trigeminal ganglion showed these primary afferents to be unaffected by diabetes. These findings suggest that central amplification can substantially transform ascending sensory input in diabetes, even in the absence of a barrage of ectopic primary afferent activity.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Oliver J
authors.identifier: 0000-0003-4009-282X
authors.initials: OJ
authors.lastname: Freeman
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Mathew H
authors.initials: MH
authors.lastname: Evans
authors.affiliation: Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK.|Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.|School of Biological Sciences, University of Auckland, Auckland, New Zealand.|Medical Sciences Division, Department of Pharmacology, University of Oxford, Oxford, UK.
authors.forename: Garth J S
authors.initials: GJ
authors.lastname: Cooper
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Rasmus S
authors.initials: RS
authors.lastname: Petersen
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Natalie J
authors.identifier: 0000-0001-8287-1181
authors.initials: NJ
authors.lastname: Gardiner
mesh_terms: D000200:Action Potentials; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013787:Thalamic Nuclei / Q000166:cytology / Q000503:physiopathology*; D014738:Vibrissae / Q000294:innervation / Q000502:physiology
keywords: neuropathy; rat; somatosensory; streptozotocin; thalamus