In peripheral neuropathies such as diabetic polyneuropathy, impairments of microcirculation due to autonomic dysfunction and small fiber pathology often coincide. The contribution of the autonomic nervous system to pain pathophysiology and the interaction of sympathetic efferents with sensory afferents has been subject of controversial debate for years. This presentation will highlight changes in cutaneous sensory and sympathetic vaso- and sudomotor innervation in peripheral neuropathic pain conditions using advanced quantification of cutaneous somatosensory and sympathetic innervation. To this end, skin biopsies have been examined in patients with diabetic polyneuropathy. Specifically, sudomotor function have been investigated through quantification of the sweat gland volume and innervation. Vasomotor function and microvascular integrity will be assessed by quantification of neurovascular contacts and vessel density, respectively. The findings will be correlated with signs and symptoms, measures of autonomic function (e.g., SUDOSCAN©) and sensory profiles of meticulously phenotyped patients with diabetic polyneuropathy with and without pain.