Activation of trigeminal ganglion satellite glial cells in CFA-induced tooth pulp pain in rats

Abstract

This study further investigated the mechanisms underlying the rat model of tooth pulp inflammatory pain elicited by complete Freund’s adjuvant (CFA), in comparison to other pulpitis models. Pulps of the left maxillary first molars were accessed. In the CFA group, the pulps were exposed, and CFA application was followed by dental sealing. In the open group, the pulps were left exposed to the oral cavity. For the closed group, the pulps were exposed, and the teeth were immediately sealed. Naïve rats were used as negative controls. Several parameters were evaluated at 1, 2, 3 and 8 days. There was no statistical significant difference among the groups when body weight variation, food or water consumption were compared. Analysis of serum cytokines (IL-1β, TNF or IL-6) or differential blood cell counts did not reveal any evidence of systemic inflammation. The CFA group displayed a significant reduction in the locomotor activity (at 1 and 3 days), associated with an increased activation of satellite glial cells in the ipsilateral trigeminal ganglion (TG; for up to 8 days). Amygdala astrocyte activation was unaffected in any experimental groups. We provide novel evidence indicating that CFA-induced pulp inflammation impaired the locomotor activity, with persistent activation of ipsilateral TG satellite cells surrounding sensory neurons, without any evidence of systemic inflammation or amygdala astrogliosis.

Role of transient receptor potential vanilloid type 1 in the trigeminal ganglion and brain stem following dental pulp inflammation

“…Recently, CFA has been frequently used to study pulpal pain (Matsuura et al 2013, Filippini et al 2018, Watase et al 2018. Further, a rapid onset of definitive pain was observed.…”

Polarization of macrophages in the trigeminal ganglion of rats with pulpitis

“…CFA is a mixture of mineral oils containing heat‐inactivated Mycobacterium tuberculosis, which has been widely used to induce chronic inflammatory pain when injected into the rat tooth pulp 16,17 . CFA induced pulpitis is a developmental process, including the development of pulpitis to apical periodontitis and alveolar bone inflammation, as well as the repair process of inflammatory injury at the later stage.…”

“…The studies found that after applying complete Freund's adjuvant (CFA) to induce pulpitis, macrophages were activated in the TG. The innervation of single TG neurons to multiple pulps was involved in enhancing the activity of TG neurons in adjacent non inflammatory teeth, resulting in ectopic persistent dental pulp pain 16 . Therefore, the interaction between activated macrophages and neurons in the TG may be the key to regulate pulpitis pain and repair of nerve injury.…”

Glia and Orofacial Pain: Progress and Future Directions

“…It is now well known that activation, proliferation, and inflammatory signaling in microglia and astrocytes within the TN and SGCs within the TG are important mechanisms for the maintenance of pathological orofacial pain, as demonstrated using preclinical pain models [127]. More than 20 years ago, Byers and colleagues found a marked upregulation of GFAP staining in the TG after pulp injury, and the work has been replicated by other groups [45,128]. The increased expression of activated satellite glia cells in the TG, as measured by GFAP expression, can occur adjacent to the neurons innervating the injured or inflamed pulp, as well as neurons innervating adjacent, non-injured teeth [113,129].…”