Central serotonin 3 receptors play an important role in the modulation of nociceptive neural activity of trigeminal subnucleus caudalis and nocifensive orofacial behavior in rats with persistent temporomandibular joint inflammation

The role of central serotonin 3 receptors on neural activities recorded from superficial laminae of trigeminal subnucleus caudalis/upper cervical spinal cord junction region was investigated using rats with (Complete Freund's Adjuvant day 7 group) or without (non-Complete Freund's Adjuvant group) persistent temporomandibular joint inflammation evoked by Complete Freund's Adjuvant for 7 days. We identified two types of units, Deep-wide dynamic range units and Skin-wide dynamic range units from extracellular recordings. Deep-wide dynamic range units have mechanoreceptive fields in the deep craniofacial tissues including masseter muscle but do not have cutaneous mechanoreceptive fields. Deep-wide dynamic range unit discharges evoked by the formalin injection into masseter muscle were significantly enhanced in the late phase in Complete Freund's Adjuvant day 7 group. Discharges of Skin-wide dynamic range units evoked by the noxious pinch stimulation to facial skin in Complete Freund's Adjuvant day 7 group were significantly enhanced compared with those in non-Complete Freund's Adjuvant group. Topical administration of central serotonin 3 receptor antagonist, tropisetron, onto trigeminal subnucleus caudalis/upper cervical spinal cord junction region significantly reduced both formalin-evoked Deep-wide dynamic range unit and pinch-evoked Skin-wide dynamic range unit discharges in non-Complete Freund's Adjuvant and Complete Freund's Adjuvant day 7 groups significantly. The inhibitory effects of tropisetron on pinch-evoked Skin-wide dynamic range unit discharges were prolonged in Complete Freund's Adjuvant day 7 group compared with those in non-Complete Freund's Adjuvant group. The role of central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical spinal cord junction region was also tested by orofacial formalin test in Complete Freund's Adjuvant day 7 group. Intracisternal administration of tropisetron decreased the orofacial nocifensive behavior in the late phase evoked by the injection of formalin into the masseter muscle. These results suggest that central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical spinal cord junction region are involved in mediating pronociceptive effects in both superficial and deep craniofacial tissues nociception during persistent temporomandibular joint inflammation.