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(180) Plasma endogenous enkephalin levels in systemic sclerosis patients

2008; Elsevier BV; Volume: 9; Issue: 4 Linguagem: Inglês

10.1016/j.jpain.2008.01.100

1528-8447

Terry A. McNearney, Kathleen A. Sluka, Michel Fischbach, Chang Ho Ahn, Mark Mayes,

Coagulation, Bradykinin, Polyphosphates, and Angioedema

Met-and leu-enkephalins are endogenous opioid neuropeptides with potent analgesic, vasoactive and immunomodulatory properties. We hypothesized that clinical or immunological abnormalities of systemic sclerosis (SSc) patients might be correlated to plasma enkephalin levels. Plasma samples were collected from people with SSc (N=17) and matched normal controls (N=16). Plasma met-enkephalin and leu-enkephalin levels (ug/ml) were measured by high performance liquid chromatography (HPLC). Additionally, plasma samples collected at study entry of the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort (early SSc, N=136) were measured and correlated to database parameters. Statistical analyses were performed by Student’s t-tests and Pearson correlation coefficients. The results were as follows: 1. SSc patient vs matched normal controls study: SSc patients had significantly lower plasma met-enkephalin levels (0.16+0.10 vs 0.28+0.14 ug/ml, p=0.05) and lower plasma leu-enkephalin levels (1.04+0.90 vs 2.45+0.10 ug/ml, respectively, p<0.03). 2. GENISOS samples: Significantly lower plasma met-enkephalin levels were associated with anti-topoisomerase I seropositivity (6+8.3 vs 14.9+22.8 ug/ml, p=0.02). Plasma leu-enkephalin levels were significantly higher in SSc patients with digital pulp loss (95.6+130 vs 64.9+101 ug/ml, p=0.02). Generally, plasma leu-enkephalin levels were severalfold higher than plasma met-enkephalin levels. Lower mean plasma met-enkephalin levels and inversely higher leu-enkephalin levels were noted (p=NS) in SSc patients with Raynaud’s phenomena, digital gangrene, pulmonary fibrosis and pulmonary hypertension. Lower plasma levels of endogenous enkephalins in small SSc vs matched control groups may reflect depressed synthesis or increased degradation related to ongoing neurogenic, vasogenic or fibrogenic processes. The associations of plasma enkephalin levels to immunologic or clinical pathologies may underscore their physiologic significance in SSc. Supported by NIH Specialized Center of Research (SCOR) Grant in Scleroderma P50AR44888 (TAM, CA, MDM), NIH Centers for Research Translation (CORT) P50AR054144 (TAM, CA, MDM), University Clinic Research Center Grants M01-RR00073 (UTMB), M01-RR02558 (UTH-HSC), M01-RR01346 (UT-SA), NIH K0202201 (KAS), NS39734 (KAS), AR052316 (KAS).