ABSTRACT
Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.
Subject(s)
Animals , Male , Mice , Chloroquine , Toxicity , Disease Models, Animal , Dose-Response Relationship, Drug , Etanercept , Therapeutic Uses , Ganglia, Spinal , Metabolism , Mice, Inbred C57BL , Mice, Transgenic , Pruritus , Drug Therapy , Metabolism , Pathology , RNA, Messenger , Metabolism , Receptors, Tumor Necrosis Factor, Type I , Genetics , Receptors, Tumor Necrosis Factor, Type II , Genetics , Signal Transduction , Skin , Metabolism , Spinal Cord , Metabolism , Thalidomide , Therapeutic Uses , Time Factors , Tumor Necrosis Factor-alpha , Genetics , Metabolism , p-Methoxy-N-methylphenethylamine , ToxicityABSTRACT
Objective To compare the efficacy of holmium laser and traditional surgery for the treatment of varicosis of the lower limbs.Methods From March 2005 to December 2006,226 patients with varicosis of the lower limbs(274 limbs)were treated using holmium laser(laser group,120 patients with 148 diseased limbs)or high ligation and stripping of the great saphenous vein(traditional group,106 patients with 126 diseased limbs).Results The mean operation time of the laser group was significantly shorter than that in the traditional group [(38.0?10.8)min vs(61.5?12.3)min,t=-15.294,P=0.000].None of the patients in the laser group need analgetics after the operation,while 58 patients in the traditional group received the drug after the surgery(0 vs 54.7%,?2=88.329,P=0.000).The patients in the laser group returned to activities earlier and had shorter postoperative hospital stay than those in the traditional group [(6.2?0.8)h and(3.0?0.5)d vs(22.5?1.5)h and(8.5?2.5)d;t=-105.034,P=0.000 and t=-23.632,P=0.000,respectively].The rates of complications and 1-year recurrence were similar in the two groups [16.9%(25/148)vs 18.3%(23/126),?2=0.087,P=0.768 and 3.8%(3/78)vs 3.1%(2/65),?2=0.000,P=1.000].Conclusions Holmium laser has advantages of shorter operation time and hospital stay,fewer surgical incisions,milder postoperative pain,and earlier return to activities.Closure of the great saphenous vein is the key to ensure the effect of laser therapy.High ligation of the great saphenous vein should be done simultaneously if necessary.