Thalamic Neuronal Dysfunction in Diabetic Peripheral Neuropathy
Abstract Number: 0002-OR
Authors: RAJIV A. GANDHI, DINESH SELVARAJAH, CELIA EMERY, PAUL GRIFFITHS, IAN WILKINSON, SOLOMON TESFAYE, Sheffield, United Kingdom
Results: Pain is the most distressing symptom of diabetic peripheral neuropathy (DPN). Although pathological abnormalities have been identified at the level of the peripheral nerve and spinal cord in DPN, there is limited understanding of why some patients suffer severe chronic pain whilst others have painless symptoms. A better understanding of the pathogenesis of pain in DPN is crucial for the development of novel, mechanism-based treatments. The thalamus, which is the gateway to the somatosensory cortex, may have a role in the pathogenesis of painful DPN. The aim of this study was to study this using proton magnetic resonance spectroscopy (H-MRS).
Seventy-one right-handed male subjects with type 1 diabetes (17 no DPN, 19 sub-clinical DPN, 13 painful DPN and 22 painless DPN) underwent detailed clinical and neurophysiological assessments (Dyck staging criteria; NIS(LL)+7). H-MRS of the left thalamus was performed to measure established markers (N-acetyl aspartate [NAA] compounds) of neuronal function using long echo time (LTE) and neuronal integrity using short echo time (STE) sequences. At LTE, NAA is expressed as a ratio to creatine (Cr), which represents a relative internal constant.
At LTE (see figure below), subjects with painless DPN had lower NAA/Cr (1.55+0.21 [mean+SD]) compared to those with no DPN (1.90+0.21, p<0.001). Subjects with painless DPN also had lower NAA/Cr compared to those with sub-clinical DPN (1.75+0.29) and painful DPN (1.80+0.23), p<0.05. There were no differences between these 2 groups and the no DPN group (p>0.2). There were no significant inter-group differences at STE.
The majority of ascending sensory nerve fibre tracts terminate in the thalamus before projections are sent out to higher cortical centres. These results imply that there is a change in neuronal physiology or function, rather than neuronal loss, within the thalamus in painless but not painful DPN. It is possible that relative preservation of thalamic neuronal function is necessary for the transmission of abnormal peripheral signals to higher centres, in order to be able to perceive chronic pain in DPN.