Table 1.

Recently reported differences between painful- and painless-diabetic peripheral neuropathy

Contributing factor	Difference associated with painful-DPN	References
Risk factors	Female gender	[21••, 26, 27••, 28••]
	Nephropathy	[26, 27••]
	Nav 1.7 mutations	[35•]
Small nerve fiber alterations	Hyposensitivity phenotype	[23••, 27••]
	Epidermal nerve fiber regeneration	[49, 50•, 51]
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.	[86, 117•, 121]
Central nervous system
Spinal cord	Impaired spinal inhibitory function	[62•]
Thalamus	Preserved thalamic NAA and GABA neurochemistry	[135, 136]
	Thalamic hyperperfusion	[137•]
	Altered somatosensory cortex and thalamic functional connectivity	[138]
Descending modulatory pain centers	Descending pain facilitation	[142, 143•]
Higher brain centers	Somatomotor cortex and insula cortical atrophy	[146]
	Abnormal cerebral blood flow at rest and in response to heat pain	[142, 148]
	Altered functional connectivity in higher brain centers at rest and experimental pain conditions	[147, 149, 150]

DPN diabetic distal symmetrical polyneuropathy, NAA N-acetyl aspartate, GABA γ-aminobutyric acid, BOLD