Occlusal Trauma Induces Neuroimmune Crosstalk for a Pain State

Abstract

Temporomandibular joint (TMJ) disorder caused by occlusal trauma is one of the most controversial topics in dentistry. Experimental traumatic occlusion (ETO) induced by metal crowns cemented to mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-α, IL-1β, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28 d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1β and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization.

Novel Apocynin regulates TRPV1 activity in the trigeminal system and controls pain in a temporomandibular joint neurogenic model

“…Also, rats were placed into the test chamber for 10 minutes due to the habituation process for the new environment. On the day test, rats were previously anesthetized by inhalation of iso urane, and the intra-temporomandibular joint (TMJ) injection was performed as previously described (Abdalla et al, 2022). Rats were placed back to the test chamber to completely regain consciousness (30-60s after discontinuing the anesthesia), and then the nociceptive response was evaluated over 30 minutes.…”

“…Protein lysates from trigeminal ganglion samples for western blotting reactions were performed as previously described (Abdalla et al, 2022). Thirty micrograms of each protein lysate were probed with primary antibodies against anti-TRPV1 (1:500; Alomone Labs), anti-transient receptor potential ankyrin 1 (TRPA1) (1:500; Alomone Labs), anti-transient receptor potential melastin 8 (TRPM8) (1:250; Alomone Labs), p38 MAPK (1:1.000; Cell Signaling), p44/42 MAPK (1:1.000; Cell Signaling), SAPK/JNK (1:1.000; Cell Signaling), Phospho-p38 MAPK (Thr180/Tyr182; 1:1.000; Cell Signaling), Phospho-p44/42 MAPK (Erk1/2; 1:1000, Cell Signaling), Phospho-SAPK/JNK (Thr183/Tyr185; 1:1000, Cell Signaling), and GAPDH (1:1.000, Cell Signaling).…”

Pain-sensorimotor interactions: New perspectives and a new model

“…In contrast with the acute pain models, these chronic models are typically associated with a more complex array of spontaneous and evoked behaviors, including sensorimotor behaviors analogous to some of those noted above for chronic pain models in the spinal sensorimotor system and reflecting features such as allodynia or hyperalgesia as well as peripheral and/or central sensitization ( Cairns et al, 2014 , Dostrovsky et al, 2014 , Dubner et al, 2014 , Shinoda et al, 2019 , Chung et al, 2020 , Sessle, 2021 ). These nocifensive sensorimotor behaviors may include changes in grooming and exploratory activity, facial grimacing, increased licking and guarding behaviors, and disruptions in chewing, biting, feeding, drinking, or other motor behaviors as well as operant responses involving complex craniofacial behaviors ( Abdalla et al, 2022 , Chung et al, 2020 , Dubner et al, 2014 , Ro, 2005 , Rocha Barreto et al, 2022 , Sessle, 2021 , Shinoda et al, 2019 ). It is notable that, like the pain models used in the spinal sensorimotor system, sex differences and inter-individual variability in pain-related sensorimotor behavior are not uncommon in the acute or chronic craniofacial pain models ( Cairns, 2007 , Cairns et al, 2014 , Zhang et al, 2014 , Sessle, 2021 ).…”

Peripheral role of glutamate in orofacial pain

“…Glutamate increases in the TG following a chronic constriction injury of the inferior orbital nerve, which can be released within the TG and can contribute to nociception ( Kung et al, 2013 ). Experimental traumatic occlusion causes a long-lasting nociceptive response, in which the release of glutamate increases, and AMPA and NMDA receptors are upregulated in the TG ( Abdalla et al, 2022 ). Since EAATs are expressed by SGCs in the TG ( Miller et al, 2011 ; Laursen et al, 2014 ), it is likely that SGCs participate in regulating intra-ganglionic glutamate levels.…”