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Cleavage of SNAP‐25 ameliorates cancer pain in a mouse model of melanoma
Author(s) -
Olbrich K.,
Costard L.,
Möser C.V.,
Syhr K.M.J.,
KingHimmelreich T.S.,
Wolters M.C.,
Schmidtko A.,
Geisslinger G.,
Niederberger E.
Publication year - 2017
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.904
Subject(s) - snap , melanoma , cleavage (geology) , medicine , cancer research , biology , computer science , computer graphics (images) , paleontology , fracture (geology)
Background Cancer pain is associated with increased pain sensitivity to noxious (hyperalgesia) and normally innocuous (allodynia) stimuli due to activation of nociceptors by tumour‐derived mediators or tumour infiltration of nerves. The pain sensitization is accompanied by modifications in gene expression, but specifically regulated genes are largely unknown. The 25 kDa synaptosomal‐associated protein ( SNAP ‐25) is involved in chemical neurotransmission at the synaptic cleft. Its inhibition by Botulinum neurotoxin A (Bo NT /A) has been associated with antinociceptive effects in migraine, inflammatory and neuropathic pain. However, its potential to reduce tumour‐associated pain remains to be clarified. Methods We applied a melanoma model of tumour pain in C57 BL /6 mice and investigated SNAP ‐25 expression and regulation by qRT ‐ PCR , Western Blot and immunofluorescence as well as tumour‐associated mechanical allodynia with and without Bo NT /A treatment. Results We found increased SNAP ‐25 expression in the dorsal root ganglia and the sciatic nerve. Intraplantar injection of Bo NT /A induced the cleavage of SNAP ‐25 in these tissues and was associated with decreased mechanical allodynia after therapeutic treatment at early and late stages of tumour pain while the tumour size was not affected. Conclusions Our data indicate that SNAP ‐25 plays a role in tumour pain but has no influence on the initiation and progression of skin cancer. Its cleavage inhibits the development of allodynia in the mouse melanoma model and might be useful as new therapeutic approach for the treatment of cancer pain. What does this study add? SNAP‐25 is differentially regulated during melanoma‐induced tumour pain. Its cleavage by Bo NT /A might be a suitable therapeutic option for tumour pain patients since tumour‐associated pain can be strongly and significantly reduced after preventive and therapeutic Bo NT /A treatment, respectively.