TMJ inflammatory pain is associated with microglia activation and neuroinflammation

Objectives Recent research has provided much evidence that the trigeminal ganglion (TG) is a crucial component of the trigeminal pain pathway, modulating and amplifying the pain signal by way of a network of non-synaptic cellular interaction. Persistent or severe stimulation of this system is believed to lead to chronic pain states, however the nature of this cellular interaction and their role in pain process is not known. The aim of this study is to define the role of TG neuronal and non-neuronal cells in temporomandibular joint (TMJ) inflammatory pain model.Methods The TMJ of mice were injected unilaterally with either complete or incomplete Freund’s adjuvant (IFA or CFA), or did not receive an injection. Behavioural analysis was carried out using cheek wiping as an indicator of pain experience. 7 days post-injection, the TMJ tissue was processed for Western blotting for IL-1β, and trigeminal ganglion samples were processed for immunohistochemistry. The activation state of microglia in the trigeminal ganglion was analysed by comparing staining intensity of Iba1 (microglia marker), and the mean neuronal cell soma size was compared by staining for PGP9.5 (neuronal cell marker). Results Behavioural analysis and Western blotting indicated painful inflammation in the ipsilateral TMJ of CFA-injected mice. Microglial activation was significantly increased in CFA-injected mice compared to naïve mice. The neurons showed a trend of decreasing mean soma size from naïve to IFA- to CFA-injected mice. Conclusions The results of this study provided evidence that microglia activation is associated with TMJ pain. The observed sprouting of small diameter nociceptive neurons is not unexpected but further research is required to determine the role of microglia in neuronal phenotypic changes observed and identify drugable targets for pain relief.