Activation of microglial cells in the trigeminal subnucleus caudalis evoked by inflammatory stimulation of the oral mucosa

The mucous membrane surface lining of the oral cavity is constantly exposed to micro-environmental changes elicited by a variety of physical, chemical, microbiological and thermal stimulation. In the oral cavity, there are many kinds of receptors involved in nocifensive (e.g., pain-related) behaviors maintained by mechanisms to escape from noxious events. Because pain sensation deteriorates the quality of life (QOL), the task to elucidate nociceptive mechanisms, which evoke, enhance or hypersensitize pain, is an important assignment. Some previous studies have reported that hypodermic injection of tumor necrosis factor (TNFα; an inflammatory mediator cytokine) into tissue distributed with C fibers would upregulate IL-1β to evoke inflammatory hyperalgesia1)–7). Additionally, we observed the enhanced expression of TRPV4, serotonin (5-hydroxytryptamine: 5HT) and phosphorylated-extracellular signal-regulated kinase (pERK) —a mitogen activated-protein kinase (MAPK)— in many parts of the brainstem, and confirmed that the expression of TRPV4 and pERK in the trigeminal subnucleus caudalis (Vc) was closely related with central hyperalgesia and descending noradrenergic and serotonergic endogenous pain inhibitory systems evoked by nociceptive stimulation8). The pERK has been recognized as a marker of activation of spinal dorsal horn (DH) neurons following a variety of peripheral noxious stimuli9, 10). There have been many studies reported that the Vc glia were activated to elicit central sensitization, while dental pulp injuries induced plastic neuronal changes of astrocytes in the Vc11)–14). Astrocytes and microglia in the central nervous system (CNS) were activated either by inflammation or peripheral injury, and the activity of spinal glia was deeply involved with activation mechanisms of p38 MAPK to evoke inflammatory pain, hyperalgesia and allodynia15)–17). Other studies also observed that both peripheral inflammation and nerve damage prominently increased the number of microglial markers and phosphorylated(phospho-) p38 MAPK-IR glia in the spinal cord, while application with 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580, Okajimas Fol a An t. Jpn., 89(4): 137–145, February, 2013