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Cutaneous Microdialysis as a Novel Means of Continuously Stimulating Eccrine Sweat Glands In Vivo

2006; Elsevier BV; Volume: 126; Issue: 6 Linguagem: Inglês

10.1038/sj.jid.5700197

1523-1747

Caroline J. Morgan, Peter S. Friedmann, Martin K. Church, Geraldine Clough,

Advancements in Transdermal Drug Delivery

Previous studies of the pharmacological regulation of sweat gland function in humans have administered agonists or antagonists systemically, by local intradermal injection or by iontophoresis. This has not allowed prolonged or steady-state activation of sweat glands to be examined. In this study, we used the technique of dermal microdialysis to administer pharmacological agents singly and in combination for up to 5 hours. Muscarinic stimulation with pilocarpine nitrate (50 μg ml−1 to 1.66 mg ml−1) produced a sigmoid dose response curve, with maximal sweating (measured as transepidermal water loss) (mean 70 g m−2 hour−1) after 15 minutes. This was sustained at steady-state levels (55 g m−2 hour−1) until perfusion stopped. Perfusion with atropine (0.003 mg ml−1) reduced sweating below baseline and blocked pilocarpine-induced sweating completely. Noradrenaline (0.005 mg ml−1) induced much lower sweat rates than pilocarpine (56.8±1.62 g m−2 hour−1 vs 8.2±1.2 g m−2 hour−1, respectively, P<0.001) and this was unaffected by co-administration of atropine. This method has made it possible to show that sweat glands are capable of sustaining near maximal activity for at least 5 hours. The method has future application in investigation of conditions with disordered sweat gland activity. Previous studies of the pharmacological regulation of sweat gland function in humans have administered agonists or antagonists systemically, by local intradermal injection or by iontophoresis. This has not allowed prolonged or steady-state activation of sweat glands to be examined. In this study, we used the technique of dermal microdialysis to administer pharmacological agents singly and in combination for up to 5 hours. Muscarinic stimulation with pilocarpine nitrate (50 μg ml−1 to 1.66 mg ml−1) produced a sigmoid dose response curve, with maximal sweating (measured as transepidermal water loss) (mean 70 g m−2 hour−1) after 15 minutes. This was sustained at steady-state levels (55 g m−2 hour−1) until perfusion stopped. Perfusion with atropine (0.003 mg ml−1) reduced sweating below baseline and blocked pilocarpine-induced sweating completely. Noradrenaline (0.005 mg ml−1) induced much lower sweat rates than pilocarpine (56.8±1.62 g m−2 hour−1 vs 8.2±1.2 g m−2 hour−1, respectively, P<0.001) and this was unaffected by co-administration of atropine. This method has made it possible to show that sweat glands are capable of sustaining near maximal activity for at least 5 hours. The method has future application in investigation of conditions with disordered sweat gland activity. transepidermal water loss