Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus.

Giovanni Villa,Stefania Ceruti,Maria P Abbracchio,Luc Jasmin,Giulia Magni,Matteo Zanardelli,Peter T Ohara

doi:10.1186/1744-8069-6-89

Giovanni Villa, Stefania Ceruti + Show 5 more

Open Access

https://doi.org/10.1186/1744-8069-6-89

Copy DOI

Abstract

BackgroundGlial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS). Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA) into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity.ResultsCFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression.ConclusionsOur data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

Highlights

Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS)
While there was no difference in the dye concentration in the temporomandibular joint (TMJ) of rats injected with saline (0.07 ± 0.07 μg/ml for the ipsilateral side vs. 0.07 ± 0.06 μg/ml for the contralateral side, p = 0.977; n = 7 animals) (Figure 1A), a significantly greater amount of dye was extracted from the ipsilateral TMJ of Complete Freund’s Adjuvant (CFA)-injected rats, both at 24 h p.i
satellite glial cells (SGCs) and macrophages are selectively activated in trigeminal ganglia following TMJ inflammation We evaluated the morphological and biochemical consequences of the induction of TMJ inflammation in the trigeminal ganglion (TG), with particular focus on SGCs [33]

Summary

Introduction

Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS). Despite efforts in the last decades towards the understanding of its pathophysiology and the development of new drugs, chronic pain still remains a difficult to manage and disabling condition. The reason for this failure may be in part due to the fact that most of the available drugs target neurons [2,3], whereas increasing evidence indicates. An increased expression of interleukin (IL)-6 [19] and of other pro-inflammatory cytokines [20] is detected in SGCs. DRG neurons release chemokines that trigger macrophage invasion, suggesting that the latter cell population is involved in the regulation of chronic pain [21,22,23]

Methods

Results

Discussion

Conclusion