Up-regulation of IL-1β and sPLA2-III in the medial prefrontal cortex contributes to orofacial and somatic hyperalgesia induced by malocclusion via glial-neuron crosstalk.

The medial prefrontal cortex (mPFC) has been identified as a key brain region involved in the modulation of chronic pain. Our recent study demonstrated that unilateral anterior crossbite (UAC) developed the comorbidity model of temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS), which was characterized by both orofacial and somatic hyperalgesia. In the present study, UAC rats exhibited significant changes in gene expression in the mPFC. Enrichment analysis revealed that the significantly involved pathways were cytokines-cytokine receptor interaction and immune response. The expression of group III secretory phospholipase A2 (sPLA2-III) was significantly increased in the mPFC of UAC rats. Silencing sPLA2-III expression in the mPFC blocked the orofacial and somatic hyperalgesia. Immunofluorescence showed that sPLA2-III was mainly localized in neurons. The expression of interleukin-1β (IL-1β) in the mPFC significantly increased after UAC. Injection of IL-1β antibody into the mPFC blocked orofacial and somatic hyperalgesia. IL-1β was mainly localized in microglia cells. Furthermore, injection of IL-1β antibody significantly reduced the expression of sPLA2-III. These results indicate that neuroinflammatory cascade responses induced by glial-neuron crosstalk in the mPFC may contribute to the development of TMD and FMS comorbidity, and IL-1β and sPLA2-III are identified as novel potential therapeutic targets for the treatment of chronic pain in the comorbidity of TMD and FMS.
Competing Interests: Declaration of competing interest I, along with my coauthors hereby declare that there is no conflict of interest associated with this research. I have not received any financial support or sponsorship, nor have we been employed or hold any position in any organization that may influence the outcome or content of this research. We also declare that we have no personal relationships or connections that could influence the objectivity or integrity of the information presented in this research. We confirm that the views and opinions expressed in this research are my own and do not reflect the opinions or positions of any other individuals, organizations, or institutions.
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