Persistent monoarthritis of the temporomandibular joint region enhances nocifensive behavior and lumbar spinal Fos expression after noxious stimulation to the hindpaw in rats

Effects of persistent temporomandibular joint (TMJ) inflammation on nociceptive responses of remote bodily areas of the rat were investigated. Monoarthritis of the TMJ region was evoked by the injection of complete Freund’s adjuvant (CFA) into the left TMJ region. Rats without injection of CFA into the TMJ region served as controls (non-CFA group). Time spent on licking behavior evoked by the injection of formalin into the left hindpaw and withdrawal thresholds of mechanical stimulation to both sides of the hindpaw were measured during TMJ inflammation for 3 weeks. Furthermore, expression of Fos protein in the lumbar dorsal horn was immunohistochemically investigated following the injection of formalin into the hindpaw during TMJ inflammation. Formalin-evoked nocifensive behavioral activities were significantly enhanced at 10 and 14 days after CFA injection in the late phase, while the withdrawal threshold to mechanical stimulation was significantly decreased bilaterally at 8, 10 and 14 days after CFA injection. Both formalin-evoked licking behavior and mechanical withdrawal thresholds to bilateral hindpaw at 21 days after CFA injection were similar to those in the non-CFA group. The number of Fos-positive neurons in the lumbar dorsal horn ipsilateral to the formalin injection at 1 and 7 days after CFA injection into the TMJ were similar to those in the non-CFA group; however, those were significantly increased in the laminae I–II and V–VI of the lumbar dorsal horn at 14 days after CFA injection. TMJ inflammation for 7 and 14 days alone produced a small number of Fos-expressing neurons in the lumbar dorsal horn. These results provide evidence that persistent unilateral inflammation of the TMJ region causes an increase in behavioral hyperalgesia of the hindpaw, which is attributed to the modulation of neural activities, in part, in the lumbar dorsal horn, likely mediated by supraspinal neural mechanisms.