Epidermal Langerhans cells in small fiber neuropathies

• Published in: Pain (Amsterdam) Vol. 153; no. 5; pp. 982 - 989
• Main Authors: Casanova-Molla, Jordi, Morales, Merche, Planas-Rigol, Ester, Bosch, Anna, Calvo, Maria, Grau-Junyent, Josep Maria, Valls-Solé, Josep
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.05.2012; Lippincott Williams & Wilkins, Inc; Elsevier
• Subjects: Adult; Aged; Antigens, CD - metabolism; Biological and medical sciences; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Diabetic Neuropathies - metabolism; Diabetic Neuropathies - pathology; Female; Humans; Langerhans cells; Langerhans Cells - metabolism; Langerhans Cells - pathology; Lectins, C-Type - metabolism; Male; Mannose-Binding Lectins - metabolism; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neuralgia - metabolism; Neuralgia - pathology; Neuroinflammation; Neurology; Neuropathic pain; Neuropharmacology; Pain Measurement; Pharmacology. Drug treatments; Polyneuropathies - metabolism; Polyneuropathies - pathology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Skin - innervation; Skin - metabolism; Skin - pathology; Skin biopsy; Small fiber neuropathy; Ubiquitin Thiolesterase - metabolism; Langerhans cells; Skin biopsy; Small fiber neuropathy; Neuroinflammation; Neuropathic pain; Human; Nervous system diseases; Evaluation scale; Visual analogue scale; Neuropathy; Variance analysis; Pain; Skin; Localization
• ISSN: 0304-3959; 1872-6623; 1872-6623
• DOI: 10.1016/j.pain.2012.01.021

Subjects with painful small fiber neuropathy, specially in the context of diabetics, had an increased number of the proinflammatory Langerhans cells at the skin. We quantified the immune histiocytic Langerhans cells (LCs) in skin biopsy samples of patients with distal small fiber neuropathy (SFN). Patients were divided according to the presence or absence of neuropathic pain (burning pain) assessed by a visual analogue scale (VAS). We studied 13 diabetic patients (pain-DSFN), 7 nondiabetic patients (pain-SFN) who reported relevant neuropathic pain (VAS ⩾3), and 6 nondiabetic patients without neuropathic pain (no-pain-SFN). Using double immunofluorohistochemistry with the PGP 9.5 and the langerin/CD207, we quantified the intraepidermal nerve fibers density (IENFD) and LCs per square millimeter in the epidermis. A group of 10 skin samples from healthy subjects served as controls. Confocal analysis was performed to evaluate LC PGP 9.5-immunoreactivity. We found a mean value of 334.3LC/mm2 in controls, 310.2LC/mm2 in no-pain-SFN, 329.6LC/mm2 in pain-SFN and 484.3LC/mm2 in pain-DSFN (analysis of variance; P=.01). In patients, analysis of covariance adjusted by different covariables showed that the presence of diabetes (F=5.2, P=.03) was associated with an increased number of LC/mm2. There was a negative correlation between the IENFD and the number of LCs (r2=−0.13, P=.03). No statistically significant differences were found among groups of subjects either for the co-localization or for the number of LCs that were PGP 9.5-immunoreactive (analysis of variance; P>.05). These results indicate that patients with neuropathic pain in the context of SFN, specially those who had diabetes (DSFN), had an increased number of LCs in the epidermis that may play a role in the generation or maintenance of neuropathic pain.