Abstract
Irreversible pulpitis is an extremely painful condition and its consequence in the central nervous system (CNS) remains unclear. A mouse model of dental pulp injury (DPI) resembles the irreversible pulpitis profile in humans. This study sought to determine whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc), as well as increases levels of proinflammatory cytokines, and whether electroacupuncture (EA) can be a potential analgesic and neuroprotective therapy following DPI. Pain behavior was measured via head-withdrawal threshold (HWT) and burrowing behavior at days 1, 3, 7, 14 and 21 after DPI. A marked decrease in HWT and burrowing activity was observed from day 1 to 14 after DPI and no changes were seen on day 21. Microglial and astrocytes activation; along with high cytokine (TNFα, IL-1β, and IL-6) levels, were observed in the Vc at 21 days after DPI. These effects were attenuated by verum (local and distal) EA, as well as oral ibuprofen administration. The results suggest that DPI-induced pain and glial activations in the Vc and EA exert analgesic efficacy at both local and distal acupoints. Furthermore, verum (local and distal) EA might be associated with the modulations of microglial and astrocytes activation.
Highlights
Pain associated with inflammation of the dental pulp, pulpitis, is anecdotally described as “the highest level possible” [1] and is one of the most common oral diseases affecting humans worldwide and is majorly contributed by bacterial infection due to the development of caries [2]
Sci.h20a18d, 19n, xoFOsRigPEnERifiREcVaIEnWt effect on the nociceptive threshold whe3nofc17ompared to the dental pulp injury (DPI) group (Figu14re(Fi1gBur–eE1E).).OAnt adll aasyse2ss1e,dtthimeenpooicnitcs,esphatimveEAthhraedsnhooslidgniifniccanrteaefsfeecdt oannthde rneotcuicerpntievde to normal and there were no stihgrenshiofildcawnhtendcioffmepraernedcetosthine DpPaIignro-ruepl(aFtigeudreb1eBh–Ea).vOion rdsayb2e1t,wtheennocigcerpotiuveptshr(eFshigolud re 1F)
Following DPI, microglia and astrocyte shape changes were observed on day 14, which peaked on day 21 and persisted through day 28 (Figure 3A,B)
Summary
Pain associated with inflammation of the dental pulp, pulpitis, is anecdotally described as “the highest level possible” [1] and is one of the most common oral diseases affecting humans worldwide and is majorly contributed by bacterial infection due to the development of caries [2]. Microglia undergo a morphological shift from a resting to an activated state [7] These changes are usually accompanied by variations in gene signaling and expression, as well as the release of reactive nitrogen, oxygen species and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and IL-6 [8]. The World Health Organization supports acupuncture for its efficacy in several symptoms, diseases, or conditions and facial pain (including the craniomandibular disorders) [16] This novel study sought to determine for the first time whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc) of mice as well as increases levels of proinflammatory cytokines and whether electroacupuncture (EA) can be a potent analgesic and neuroprotective therapy following DPI
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