Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti‐inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia

Brain and Behavior

Jenny L. Wilkerson²  Katherine R. Gentry³  Ellen C. Dengler²  James A. Wallace²  Audra A. Kerwin²  Megan N. Kuhn²  Alexander M. Zvonok¹  Ganesh A. Thakur¹  Alexandros Makriyannis¹ 

[1] Center for Drug Discovery, Northeastern University, Boston, Massachusetts 02115;Department of Neurosciences, Health Sciences Center, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131;Department of Anesthesiology and Critical Care Medicine, Health Sciences Center, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131

关键词: CCI;    DRG;    MAGL;    pain;    paraffin immunohistochemistry;   

DOI  :  10.1002/brb3.44

来源: Wiley

【 摘 要 】

Abstract

During pathological pain, the actions of the endocannabinoid system, including the cannabinoid 2 receptor (CB₂R), leads to effective anti-allodynia and modifies a variety of spinal microglial and astrocyte responses. Here, following spinal administration of the CB₂R compound, AM1241, we examined immunoreactive alterations in markers for activated p38 mitogen-activated protein kinase, interleukin-1β (IL-1β), the anti-inflammatory cytokine, interleukin-10 (IL-10) as well as degradative endocannabinoid enzymes, and markers for altered glial responses in neuropathic rats. In these studies, the dorsal horn of the spinal cord and dorsal root ganglia were examined. AM1241 produced profound anti-allodynia with corresponding immunoreactive levels of p38 mitogen-activated kinase, IL-1β, IL-10, the endocannabinoid enzyme monoacylglycerol lipase, and astrocyte activation markers that were similar to nonneuropathic controls. In contrast, spinal AM1241 did not suppress the increased microglial responses observed in neuropathic rats. The differences in fluorescent markers were determined within discrete anatomical regions by applying spectral analysis methods, which virtually eliminated nonspecific signal during the quantification of specific immunofluorescent intensity. These data reveal expression profiles that support the actions of intrathecal AM1241 control pathological pain through anti-inflammatory mechanisms by modulating critical glial factors, and additionally decrease expression levels of endocannabinoid degradative enzymes.

【 授权许可】

CC BY-NC   
© 2012 The Authors. MicrobiologyOpen published by Blackwell Publishing Ltd.

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.