Indications of Peripheral Pain, Dermal Hypersensitivity, and Neurogenic Inflammation in Patients with Lipedema

Abstract

Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema (n = 27) and control (n = 23) consenting female volunteers. Dermal biopsies from (n = 11) Stages 1–3 lipedema and control (n = 10) participants were characterized for neuronal cell body and nociceptive neuropeptide calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) distribution. Stage 2 or 3 lipedema participants responded positively to von Frey sensitization in the calf and thigh, and Stage 3 participants also responded in the arm. Lipedema abdominal skin displayed reduced Tuj-1+ neuronal cell body density, compared to healthy controls, while CGRP and NGF was significantly elevated in Stage 3 lipedema tissues. Together, dermal neuronal cell body loss is consistent with hyper-sensitization in patients with lipedema. Further study of neuropathic pain in lipedema may elucidate underlying disease mechanisms and inform lipedema clinical management and treatment impact.

Lipohyperplasia dolorosa – neu betrachtet

“…tended to be increased compared to controls, but was not significantly different. However, LiDo patients were significantly more sensitive on the calf and arm than the controls [31]. One problematic aspect of this study, however, is that only 3 out of 5 patients in stage I reported any pain at all and only 8 out of 13 patients in stage II; only the 16 patients in stage III reported consistent pain.…”

“…The etiology of peripheral neuropathy involves reduced intradermal neuronal density [32,33]. The authors counted the number of Tuj1-positive cell bodies per skin length from thigh tissue biopsies and found no difference in density between control and LiDo samples; surprisingly, there were also no differences in cell body density between LiDo stages [31]. This finding actually contradicts neuropathic pain.…”

“…Oftmals wird darin der Schmerz mit der angenommenen Entzündung bei LiDo in Verbindung gebracht, ohne dass dafür schlüssige Beweise vorgelegt werden. Die bislang detailliertesten Untersuchungen lassen jedoch den Schluss zu, dass es sich eben nicht um einen entzündlichen oder neuropathischen Schmerz handelt [30,31].…”

“…Another aspect is reports of a burning sensation, suggesting that neurogenic inflammation plays an important role in LiDo [31,48]. The increased pain perception typical of LiDo was attributed to a dysregulation of the locoregional sensory nerve fibers (neurogenic inflammation) by an inflammatory mechanism.…”

“…Often, pain is associated with the assumed inflammation in LiDo, without conclusive evidence being presented for this. However, the most detailed examinations to date suggest that it is not an inflammatory or neuropathic pain [30,31].…”