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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Neuronal toll like receptor 9 contributes to complete Freund's adjuvant-induced inflammatory pain in mice
Yu Chen1, Hui Chen1, Xiao-Chen Li1
1Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institute of Acupuncture Research, Institutes of Integrative Medicine, Fudan University, Shanghai, China.
Abstract:
Toll like receptor 9 (TLR9) is a critical sensor for danger-associated molecular patterns (DAMPs) and a crucial marker of non-sterile/sterile inflammation among all TLRs. However, the significance of TLR9 in inflammatory pain remains unclear. Here, we subcutaneously injected Complete Freund's adjuvant (CFA) into the plantar surface of the hind paw, to established a mouse model of inflammatory pain, and we examined expression and distribution of TLR9 in this model. There was a significant increase of TLR9 mRNA and reduction of mechanical paw withdrawal threshold in mice intraplantar injected with CFA. By contrast, mechanical paw withdrawal threshold significantly increased in mice treated with TLR9 antagonist ODN2088. Furthermore, TLR9 is found predominantly distributed in the neurons by immunofluorescence experiment. Accordingly, neuronal TLR9 downregulation in the spinal cord prevented CFA-induced persistent hyperalgesia. Overall, these findings indicate that neuronal TLR9 in the spinal cord is closely related to CFA-induced inflammatory pain. It provides a potential treatment option for CFA-induced inflammatory pain by applying TLR9 antagonist.
Insights
Toll-like receptor 9 (TLR9) plays a key role in inflammatory pain. Blocking TLR9 in the spinal cord reduced pain sensitivity in a mouse model, suggesting TLR9 antagonism as a potential treatment for inflammatory pain.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Toll-like receptor 9 (TLR9) is recognized for its role in sensing danger signals and mediating inflammation.
- The specific involvement of TLR9 in the mechanisms underlying inflammatory pain has not been fully elucidated.
Purpose of the Study:
- To investigate the role of TLR9 in the development of inflammatory pain using a Complete Freund's adjuvant (CFA)-induced mouse model.
- To determine the expression, distribution, and functional significance of TLR9 in the context of inflammatory hyperalgesia.
Main Methods:
- Establishment of an inflammatory pain model in mice via intraplantar injection of CFA.
- Assessment of mechanical paw withdrawal thresholds to evaluate pain sensitivity.
- Examination of TLR9 mRNA expression and protein distribution using immunofluorescence.
- Administration of a TLR9 antagonist (ODN2088) to assess its effect on pain.
Main Results:
- CFA injection led to increased TLR9 mRNA levels and decreased mechanical withdrawal thresholds, indicating hyperalgesia.
- Treatment with the TLR9 antagonist ODN2088 significantly increased mechanical withdrawal thresholds.
- Immunofluorescence revealed predominant TLR9 distribution in neurons within the spinal cord.
- Downregulation of neuronal TLR9 in the spinal cord attenuated CFA-induced persistent hyperalgesia.
Conclusions:
- Neuronal TLR9 in the spinal cord is significantly associated with the development and maintenance of CFA-induced inflammatory pain.
- Targeting neuronal TLR9, potentially through antagonism, offers a promising therapeutic strategy for managing inflammatory pain conditions.
