leukotriene-b4 and Neurogenic-Inflammation

Substance P is located in cutaneous nerve fibres and induces wheal and flare responses, accompanied by granulocyte infiltration, upon intradermal injection. Studies with animal skin and rat peritoneal mast cells have suggested that substance P induces the release of histamine and leukotriene B4 (LTB4), a potent chemoattractant for granulocytes, from skin mast cells. However, the release of LTB4 has not been detected from mast cells enzymatically isolated from human skin. In order to investigate the mechanism of granulocyte infiltration induced by substance P in human skin, we studied the release of LTB4 and histamine in response to substance P, and the effect of dexamethasone using human skin obtained from 22 nonallergic individuals. Histamine was released from all skin tissue samples in a dose-dependent manner. However, the amount of LTB4 release, both constitutive and inducible, was variable among skin preparations. Substance P induced a large release of LTB4 from the skin of eight donors (twice to six times that of the spontaneous release), but no or only negligible release from the skin of 14 donors. The amount of constitutive release of LTB4 correlated with the amount of tissue histamine. Dexamethasone selectively abolished the inducible release of LTB4, without an effect on histamine release and the constitutive release of LTB4. These results suggest that substance P induces the release of LTB4 in a certain population of human individuals by a glucocorticosteroid-dependent mechanism, and plays an important role in neurogenic inflammation with granulocyte infiltration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Chromatography, High Pressure Liquid; Dexamethasone; Epidermal Cells; Epidermis; Female; Genetic Variation; Histamine Release; Humans; Leukotriene B4; Male; Mast Cells; Middle Aged; Neurogenic Inflammation; Neutrophil Infiltration; Substance P

The pathophysiology behind chronic pain from masticatory muscles is unclear. Our hypothesis was that this pain is of inflammatory origin and associated with release of inflammatory mediators. The aim of this study was therefore to investigate the presence of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the masseter muscle and plasma and their relation to myalgia. Nineteen patients with fibromyalgia, 19 with local myalgia of the masseter muscle, and 11 healthy individuals were examined with regard to local muscular pain intensity at rest and pressure pain threshold. Inclusion criteria were masseter muscle pain for at least 3 months and masseter muscle tenderness on digital palpation. Samples were obtained from the masseter muscle by microdialysis, and the dialysates and venous blood samples were analyzed with regard to PGE2 and LTB4 concentration. Intramuscular levels were found in all groups, with significantly higher levels of LTB4 in the patients with fibromyalgia, in whom PGE2 was positively correlated to muscular pain. In the healthy individuals PGE2 was negatively correlated to pressure pain threshold. In both patient groups but not in the healthy individuals LTB4 increased during the consecutive samplings. PGE2 and LTB4 were detectable in the plasma of all groups. In conclusion, both PGE2 and LTB4 were found in the human masseter muscle. LTB4 levels are increased on needle trauma in patients with myalgia. PGE2 levels are related to muscular pain in patients with fibromyalgia. Masseter muscle pain therefore seems to be partly of peripheral inflammatory origin in fibromyalgia.

Topics: Adult; Analysis of Variance; Case-Control Studies; Chronic Disease; Dialysis; Dinoprostone; Facial Pain; Female; Fibromyalgia; Humans; Leukotriene B4; Male; Masseter Muscle; Neurogenic Inflammation; Pain Measurement; Statistics, Nonparametric