Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For a long period the therapeutic modalities to treat focal hyperhidrosis (HH) were very limited. Due to this the problem of focal HH was delt with stepmotherly. Nowadays we can consider BTX as the therapy of choice for axillary HH after topical treatment with aluminium salts have failed. The amount of successful reports on botulinum toxin (BTX) in the treatment of focal HH brought a change and the interest for this specific disorder grew. This article gives details on anatomy and physiology of sweating and mechanism of BTX. Further distinctive syndromes associated with HH, which all can be treated with BTX like localized unilateral hyperhidrosis (LUH), Ross' Syndrome and Frey' Syndrome are presented. A diagnosis of primary HH is usually based on the patients's history, typical younger age and visible signs of excessive sweating. Before treatment it is important to objectify focal HH with performing sweat tests such like Minor starch test and/or gravimetry. The total number of sweat glands is somewhere between 2 and 4 million and only about 5% are active at the same time, indicating the enormous potential for sweat production. The eccrine sweat gland is a long-branched tubular structure with highly coiled secretory portion and a straight ductular portion. Sweat is produced by clear and dark cells and is a clear hypotonic, odorless fluid. In response to nerve impulses, Acetylcholine (ACh) is released from the presynaptic nerve endings and then binds to postsynaptic cholinergic receptors presumably present in the basolateral membrane of the clear cells. This activates a complex in- and efflux of electrolytes creating the hypotonic sweat. Injection of BTX leads to temporary chemodenervation with the loss or reduction of activity of the target organ. BTX is consisted of a heavy and a light chain. The structural architecture of BTX comprises three domains-L, H(N) and H(C)-each with a specific function in the mechanism of cell intoxication. The heavy chain is responsible for binding to the nerve cell, whereas the light chain catalyzes the proteolysis of one of the three SNARE proteins (Snap-25, Vamp or Syntaxin) depending to the serotype of BTX (7 serotypes A-G). Once cleaved by BTX, the SNARE proteins cannot become part of the complex capable of mediating the vesicle membrane fusion and therefore prevents the release of ACh and hence transmission of the nerve impulse.
 ...
PMID:Anatomy of the sweat glands, pharmacology of botulinum toxin, and distinctive syndromes associated with hyperhidrosis. 1515 44

Pain is a physiological and adaptive process which occurs to protect organisms from tissue damage and extended injury. Pain sensation beyond injury, however, is a pathological process which is poorly understood. Experimental models of neuropathic pain demonstrate that reactive astrocytes contribute to reduced nociceptive thresholds. Astrocytes release "gliotransmitters" such as D-serine, glutamate, and ATP, which is extracellularly hydrolyzed to adenosine. Adenosine 1 receptor activation in the spinal cord has anti-nociceptive effects on baseline pain threshold, but the source of the endogenous ligand (adenosine) in the spinal cord is unknown. In this study we used a transgenic mouse model in which SNARE-mediated gliotransmission was selectively attenuated (called dnSNARE mice) to investigate the role of astrocytes in mediating baseline nociception and the development of neuropathic pain. Under baseline conditions, immunostaining in the dorsal horn of the spinal cord showed astrocyte-specific transgene expression in dnSNARE mice, and no difference in expression levels of the astrocyte marker GFAP and the microglia marker Iba1 relative to wild-type mice. The Von Frey filament test was used to probe sensitivity to baseline mechanical pain thresholds and allodynia following the spared nerve injury model of neuropathic pain. DnSNARE mice exhibit a reduced nociceptive threshold in response to mechanical stimulation compared to wild-type mice under baseline conditions, but nociceptive thresholds following spared nerve injury were similar between dnSNARE and wild-types. This study is the first to provide evidence that gliotransmission contributes to basal mechanical nociception.
 ...
PMID:Gliotransmission modulates baseline mechanical nociception. 2213 2