Tumor necrosis factor alpha mediates orofacial discomfort in an occlusal dental interference model in rats: The role of trigeminal ganglion inflammation

Abstract

Background: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine that plays an important role in the early stages of inflammation. In this study, we investigated its role in orofacial discomfort in rats subjected to occlusal dental interference (ODI). Methods:Female Wistar rats (180-200 g) were divided in three groups (n = 30/group):sham group, without ODI, and two experimental groups with ODI pre-treated with 0.1 mL/kg saline (ODI + SAL) or 5 mg/kg infliximab (ODI + INF) and treated every 3 days. The animals were euthanized after 1, 3, and 7 days. The number of bites and scratches and grimace scale scores were determined daily, and the bilateral trigeminal ganglion was histomorphometrically (neuronal body area) analyzed and submitted for immunohistochemistry for TNF-α, nitric oxide synthesis (NOS) neuronal (nNOS) and inducible (iNOS), peroxisome proliferator-activated receptors (PPAR) y (PPARy) and δ/β (PPARδ/β), and glial fibrillary acidic protein (GFAP). One-way/two-way ANOVA/ Bonferroni tests were used (P < .05, GraphPad Prism 5.0). Results:ODI + SAL showed a large number of bites (P = .002), scratches (P = .002), and grimace scores (P < .001) in the firsts days, and ODI + INF partially reduced these parameters. The contralateral and ipsilateral neuronal body area was significantly reduced on day 1 in ODI + SAL, but returned to the basal size on days 3 and 7, by increase in TNF-α, nNOS, PPARy, PPARδ/β, and GFAP immunostaining. The infliximab treatment attenuated these alterations (P < .05). There was no iNOS immunostaining. Conclusion:Occlusal dental interference induced transitory orofacial discomfort by trigeminal inflammatory mediator overexpression, and TNF-α blockage attenuated these processes.

Measurement properties of grimace scales for pain assessment in nonhuman mammals: a systematic review

“…The responsiveness of the MGS, RGS, RbtGS, HGS, SPFES, PGS-b, and FelGS was supported by significant changes in pain scores in response to several treatments including opioids (ie, morphine, buprenorphine, fentanyl, and tramadol), nonsteroidal anti-inflammatory drugs (ie, meloxicam, ketoprofen, diclofenac, and phenylbutazone), local anesthetics (ie, topical EMLA cream, local infiltration of bupivacaine, and intravenous regional analgesia with lidocaine or mepivacaine), anticonvulsants (ie, gabapentin), antidepressants (ie, duloxetine), and others (monoclonal antibodies, tumor necrosis factor inhibitor, and antibiotics). 1,12,34,37,39,41,48,52,69,85,88,89,97,98 In addition, for the MGS, RGS, and PGS-b, the effect of opioids in nonpainful animals was also reported to explore potential limitations of the scale (ie, whether scores could be influenced by drugs). 41,54,71,98 Responsiveness was the second-best explored measurement property of grimace scales after construct validity.…”

Celecoxib in the treatment of orofacial pain and discomfort in rats subjected to a dental occlusal interference model

“…When activated, these receptors exhibit antioxidant and anti-inflammatory activity by blocking NFkB activation and suppressing neuroinflammation 21 . PPARy reduces transcriptional activity and blocks the production of numerous cytokines such as TNF-α 22 - , 23 , which is strongly related to neuronal and behavioral changes in the head and neck region 5 and has been linked to neuroprotective actions, as reported by studies of neurodegenerative diseases (Parkinson’s, Alzheimer’s and Huntington’s) 24 .…”

“…A trained researcher manually counted the number of neuron cell bodies with positive (brownish pigmentation) and negative immunostaining for each marker. The percentage of immunopositive cells was the sampling unit 5 .…”

“…Cyclooxygenase 2 (COX-2) is an enzyme that can affect nociceptive thresholds and inflammatory pain-related symptoms 3 . Changes in the occlusal pattern may lead to an inflammatory process in periodontal tissue, whereas inflammatory changes in the trigeminal terminals may affect cell bodies in the trigeminal ganglion 4 - , 5 .…”

“…Given those changes in the occlusal pattern, dental inflammatory processes may trigger in the trigeminal system, altering animal behavior with increased signs of orofacial pain and discomfort 5 , and the control of COX-2 expression can attenuate this process 11 . The purpose of the present study was to evaluate the effect of celecoxib (a selective COX-2 inhibitor) on trigeminal ganglion changes and orofacial discomfort/nociception in rats submitted to an experimental model of dental occlusal interference (DOI).…”