Introduction
Risk Factors
Clinical Features
Cardiovascular Autonomic Neuropathy
Diagnostic Methods of Painful-DPN
Skin Biopsy
Corneal Confocal Microscopy
Evoked Responses
Quantitative Sensory Testing
Pathogenesis of Painful-DPN
Microvascular Blood Flow
Hyperglycemia and Downstream Effects
Vitamin D
Inflammation
The Central Nervous System
Spinal Cord Changes in Painful-DPN
Advanced MRI Studies of the Brain
The Thalamus
Descending Inhibition
Higher Brain Centers
Conclusions
Contributing factor | Difference associated with painful-DPN | References |
---|---|---|
Risk factors | Female gender | |
Nephropathy | ||
Nav 1.7 mutations | [35•] | |
Small nerve fiber alterations | Hyposensitivity phenotype | |
Epidermal nerve fiber regeneration | ||
Microvascular alterations | Elevated immunostaining for blood vessels | [56] |
Vitamin D | Reduced 25-hydroxyvitamin D levels | [110•] |
Inflammatory biomarkers | C-reactive protein, tumor necrosis factor-α, inducible nitric oxide synthase and interleukin 6. | |
Central nervous system | ||
Spinal cord | Impaired spinal inhibitory function | [62•] |
Thalamus | Preserved thalamic NAA and GABA neurochemistry | |
Thalamic hyperperfusion | [137•] | |
Altered somatosensory cortex and thalamic functional connectivity | [138] | |
Descending modulatory pain centers | Descending pain facilitation | |
Higher brain centers | Somatomotor cortex and insula cortical atrophy | [146] |
Abnormal cerebral blood flow at rest and in response to heat pain | ||
Altered functional connectivity in higher brain centers at rest and experimental pain conditions |