BACKGROUND: Small fiber neuropathy (SFN) is a subtype of sensory neuropathy with acral pain and normal findings in routine nerve conduction studies. METHODS: Twenty-four patients with SFN and matched controls were prospectively studied in this case-control study. Patients were assessed clinically, with standardized pain and depression questionnaires, by neurophysiologic tests, and by quantitative sensory testing. All patients underwent skin punch biopsy in a clinically affected (distal calf) and a nonaffected area (proximal thigh). Blood samples were collected for systemic cytokine gene expression analysis. RESULTS: Patients with SFN had a 2-fold higher gene expression for interleukin (IL)-2 (p < 0.0001), IL-10 (p = 0.01), and transforming growth factor-beta1 (p = 0.001) in peripheral blood. Skin samples from affected areas showed increased IL-6 (7-fold; p = 0.001) and IL-8 (5-fold; p = 0.002) gene expression when compared to healthy controls. In 10/24 patients, SFN was termed length-dependent (LD) because of a > or =5-fold higher intraepidermal nerve fiber density in the proximal than in the distal skin. Patients with LD-SFN had higher gene expression in the affected distal skin than in nonaffected skin for tumor necrosis factor-alpha (2.6-fold; p = 0.04), IL-1beta (2-fold; p = 0.02), IL-6 (>200-fold; p = 0.01), and IL-8 (>500-fold; p = 0.046). Inflammatory cells were present in most SFN samples but their numbers were not correlated with cytokine levels. CONCLUSIONS: Elevated local proinflammatory cytokines may be involved in the pathophysiology of pain in length-dependent small fiber neuropathy. These findings suggest a potential therapeutic role of locally applied cytokine inhibitors.
BACKGROUND:Small fiber neuropathy (SFN) is a subtype of sensory neuropathy with acral pain and normal findings in routine nerve conduction studies. METHODS: Twenty-four patients with SFN and matched controls were prospectively studied in this case-control study. Patients were assessed clinically, with standardized pain and depression questionnaires, by neurophysiologic tests, and by quantitative sensory testing. All patients underwent skin punch biopsy in a clinically affected (distal calf) and a nonaffected area (proximal thigh). Blood samples were collected for systemic cytokine gene expression analysis. RESULTS:Patients with SFN had a 2-fold higher gene expression for interleukin (IL)-2 (p < 0.0001), IL-10 (p = 0.01), and transforming growth factor-beta1 (p = 0.001) in peripheral blood. Skin samples from affected areas showed increased IL-6 (7-fold; p = 0.001) and IL-8 (5-fold; p = 0.002) gene expression when compared to healthy controls. In 10/24 patients, SFN was termed length-dependent (LD) because of a > or =5-fold higher intraepidermal nerve fiber density in the proximal than in the distal skin. Patients with LD-SFN had higher gene expression in the affected distal skin than in nonaffected skin for tumor necrosis factor-alpha (2.6-fold; p = 0.04), IL-1beta (2-fold; p = 0.02), IL-6 (>200-fold; p = 0.01), and IL-8 (>500-fold; p = 0.046). Inflammatory cells were present in most SFN samples but their numbers were not correlated with cytokine levels. CONCLUSIONS: Elevated local proinflammatory cytokines may be involved in the pathophysiology of pain in length-dependent small fiber neuropathy. These findings suggest a potential therapeutic role of locally applied cytokine inhibitors.
Authors: Janneke G Hoeijmakers; Catharina G Faber; Giuseppe Lauria; Ingemar S Merkies; Stephen G Waxman Journal: Nat Rev Neurol Date: 2012-05-29 Impact factor: 42.937
Authors: Lara Heij; Marieke Niesters; Maarten Swartjes; Elske Hoitsma; Marjolein Drent; Ann Dunne; Jan C Grutters; Oscar Vogels; Michael Brines; Anthony Cerami; Albert Dahan Journal: Mol Med Date: 2012-11-15 Impact factor: 6.354
Authors: Pablo Andrade; Govert Hoogland; Miguel A Garcia; Harry W Steinbusch; Marc A Daemen; Veerle Visser-Vandewalle Journal: Eur Spine J Date: 2012-09-27 Impact factor: 3.134