Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: A link to neurogenic skin disorders

Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and are associated with increased numbers and activation of mast ce lls which release vasoactive, nociceptive, and proinflammatory mediators. N ontraumatic acute psychological stress by immobilization has been shown to induce mast cell degranulation in the rat dura and colon. Moreover, intrade rmal injection of corticotropin-releasing hormone (CRH) or its analogue uro cortin (10(-5)-10(-7) M) induced skin mast cell degranulation and increased vascular permeability. Here, we investigated the effect of acute immobiliz ation stress on skin mast cell degranulation by light microscopy and electr on microscopy. Immobilization for 30 min resulted (P < 0.05) in degranulati on of 40.7 +/- 9.1% of skin mast cells compared to 22.2 +/- 7.3% in control s killed by CO2 or 17.8 +/- 2.4% in controls killed by pentobarbital. Pretr eatment intraperitoneally (ip) with antiserum to CRH for 60 min prior to st ress reduced (P < 0.05) skin mast cell degranulation to 21.0 +/- 3.3%. Pret reatment with the neurotensin (NT) receptor antagonist SR48692 reduced (P < 0.05) mast cell degranulation to 12.5 +/- 3.4%, which was significantly (P < 0.05) below control levels. In animals treated neonatally with capsaicin to deplete their sensory neurons of their neuropeptides, such as substance P (SP), mast cell degranulation due to immobilization stress was reduced t o about 15%. This is the first time that stress has been shown to trigger s kin mast cell degranulation, an action not only dependent on CRH, but appar ently also involving NT and SP. These findings may have implications for th e pathophysiology and possible therapy of neuroinflammatory skin disorders such as atopic dermatitis, neurogenic pruritus, or psoriasis, which are ind uced or exacerbated by stress. (C) 1999 Academic Press.