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@article{Yiangou:2011:10.2147/JPR.S25189,
author = {Yiangou, Y and Anand, U and Otto, WR and Sinisi, M and Fox, M and Birch, R and Foster, KA and Mukerji, G and Akbar, A and Agarwal, SK and Anand, P},
doi = {10.2147/JPR.S25189},
journal = {Journal of Pain Research},
pages = {347--355},
title = {Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons},
url = {http://dx.doi.org/10.2147/JPR.S25189},
volume = {2011},
year = {2011}
}

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TY  - JOUR
AB  - Background: There is increasing evidence that botulinum neurotoxin A may affect sensory nociceptor fibers, but the expression of its receptors in clinical pain states, and its effects in human sensory neurons, are largely unknown.Methods: We studied synaptic vesicle protein subtype SV2A, a receptor for botulinum neurotoxin A, by immunostaining in a range of clinical tissues, including human dorsal root ganglion sensory neurons, peripheral nerves, the urinary bladder, and the colon. We also determined the effects of botulinum neurotoxins A and E on localization of the capsaicin receptor, TRPV1, and functional sensitivity to capsaicin stimuli in cultured human dorsal root ganglion neurons.Results: Image analysis showed that SV2A immunoreactive nerve fibers were increased in injured nerves proximal to the injury (P = 0.002), and in painful neuromas (P = 0.0027); the ratio of percentage area SV2A to neurofilaments (a structural marker) was increased proximal to injury (P = 0.0022) and in neuromas (P = 0.0001), indicating increased SV2A levels in injured nerve fibers. In the urinary bladder, SV2A nerve fibers were found in detrusor muscle and associated with blood vessels, with a significant increase in idiopathic detrusor overactivity (P = 0.002) and painful bladder syndrome (P = 0.0087). Colon biopsies showed numerous SV2A-positive nerve fibers, which were increased in quiescent inflammatory bowel disease with abdominal pain (P = 0.023), but not in inflammatory bowel disease without abdominal pain (P = 0.77) or in irritable bowel syndrome (P = 0.13). In vitro studies of botulinum neurotoxin A-treated and botulinum neurotoxin E-treated cultured human sensory neurons showed accumulation of cytoplasmic vesicles, neurite loss, and reduced immunofluorescence for the heat and capsaicin receptor, TRPV1. Functional effects included dose-related inhibition of capsaicin responses on calcium imaging after acute treatment with botulinum neurotoxins A and E.Conclusion: Differential
AU  - Yiangou,Y
AU  - Anand,U
AU  - Otto,WR
AU  - Sinisi,M
AU  - Fox,M
AU  - Birch,R
AU  - Foster,KA
AU  - Mukerji,G
AU  - Akbar,A
AU  - Agarwal,SK
AU  - Anand,P
DO  - 10.2147/JPR.S25189
EP  - 355
PY  - 2011///
SN  - 1178-7090
SP  - 347
TI  - Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons
T2  - Journal of Pain Research
UR  - http://dx.doi.org/10.2147/JPR.S25189
UR  - http://hdl.handle.net/10044/1/29917
VL  - 2011
ER  -

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