Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type A: an organ culture study

The Journal of Headache and Pain

Research Article

Lars Edvinsson¹  Jacob Edvinsson¹  Karin Warfvinge² 

[1] Department of Medicine, Lund University, Lund, Sweden;Department of Medicine, Lund University, Lund, Sweden;Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup Hospital, Glostrup, Denmark;

关键词: CGRP;    iNOS;    IL-1β;    SNAP-25;    SV2-A;    Monoclonal antibodies;    Botulinum neurotoxin type A;   

DOI  :  10.1186/s10194-015-0555-z

 received in 2015-04-07, accepted in 2015-07-11,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundOnabotulinumtoxin type A (BoNT-A) has been found to reduce pain in chronic migraine. The aim of the present study was to ask if BoNT-A can interact directly on sensory mechanisms in the trigeminal ganglion (TG) using an organ culture method.MethodsTo induce inflammation, rat TGs were incubated for 24 hrs with either the mitogen MEK1/2 inhibitor U0126, BoNT-A or NaCl. After this the TGs were prepared for immunohistochemistry. Sections of the TG were then incubated with primary antibodies against CGRP (neuronal transmitter), iNOS (inflammatory marker), IL-1β (Interleukin 1β), SNAP-25 (synaptic vesicle docking protein) or SV2-A (Botulinum toxin receptor element).ResultsWe report that CGRP, iNOS, IL-1β, SNAP-25 and SV2-A were observed in fresh TG with a differential distribution. Interestingly, NaCl organ culture of the TG resulted in enhanced expression of CGRP and SNAP-25 in neurons and iNOS in SGCs. Co-incubation with U0126 or BoNT-A retained the increased expression of SNAP-25, while it decreased the IL-1β immunoreactivity in neurons. The iNOS expression in SGCs returned to levels observed in fresh specimens. Moreover, we observed no alteration SV2-A expression in SGCs. Thus, the overall picture is that both U0126 and BoNT-A have the ability to modify the expression of certain molecules in the TG.ConclusionWe hypothesize that chronic migraine might be associated with some degree of inflammation in the TG that could involve both neurons and SGCs. It is clinically well recognized that treatment with corticosteroids will reduce the symptoms of chronic migraine; however this remedy is associated with long-term side effects. Understanding the mechanisms involved in the expressional alterations may suggest novel ways to modify the changes and indicate novel therapeutics. The results of the present work illustrate one way by which BoNT-A may modify these expressional alterations.

【 授权许可】

CC BY   
© Edvinsson et al. 2015