-
- Dongsheng Xu, Hui Zhao, Han Gao, Huiling Zhao, Dandan Liu, and Jing Li.
- 1 Tumor Center, The First Hospital of Jilin University, Changchun, Jilin, China.
- Mol Pain. 2018 Jan 1; 14: 1744806918783535.
AbstractBackground Neuropathic pain is observed in patients as chemotherapeutic oxaliplatin is used to treat metastatic digestive tumors; however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of pathophysiology of neuropathic pain. Since the midbrain periaqueductal gray is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines system of the periaqueductal gray in regulating mechanical hyperalgesia and cold hypersensitivity evoked by oxaliplatin. Methods Neuropathic pain was induced by intraperitoneal injection of oxaliplatin in rats. ELISA and western blot analysis were used to examine pro-inflammatory cytokine levels and their receptors expression. Results IL-1β, IL-6, and TNF-α were elevated within the periaqueductal gray of oxaliplatin rats. Protein expression of IL-1β, IL-6, and TNF-α receptors (namely, IL-1R, IL-6R, and TNFR subtype TNFR1) in the plasma membrane periaqueductal gray of oxaliplatin rats was upregulated, whereas the total expression of pro-inflammatory cytokine receptors was not altered. In oxaliplatin rats, impaired inhibitory gamma-aminobutyric acid within the periaqueductal gray was accompanied with decreases in withdrawal thresholds to mechanical stimulus and % time spent on the cold plate. Our data further showed that the concentrations of gamma-aminobutyric acid were largely restored by blocking those pro-inflammatory cytokine receptors in periaqueductal gray of oxaliplatin rats; and mechanical hyperalgesia and cold hypersensitivity evoked by oxaliplatin were attenuated. Stimulation of gamma-aminobutyric acid receptors in the periaqueductal gray also blunted neuropathic pain in oxaliplatin rats. Conclusions Our data suggest that the upregulation of pro-inflammatory cytokines and membrane pro-inflammatory cytokine receptor in the periaqueductal gray of oxaliplatin rats is likely to impair the descending inhibitory pathways in regulating pain transmission and thereby contributes to the development of neuropathic pain after application of chemotherapeutic oxaliplatin.
Notes
Knowledge, pearl, summary or comment to share?You can also include formatting, links, images and footnotes in your notes
- Simple formatting can be added to notes, such as
*italics*
,_underline_
or**bold**
. - Superscript can be denoted by
<sup>text</sup>
and subscript<sub>text</sub>
. - Numbered or bulleted lists can be created using either numbered lines
1. 2. 3.
, hyphens-
or asterisks*
. - Links can be included with:
[my link to pubmed](http://pubmed.com)
- Images can be included with:
![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
- For footnotes use
[^1](This is a footnote.)
inline. - Or use an inline reference
[^1]
to refer to a longer footnote elseweher in the document[^1]: This is a long footnote.
.