Medullary Dorsal Horn Neuronal Activity in Rats with Persistent Temporomandibular Joint and Perioral Inflammation
Authors: Iwata Koichi , Tashiro Akimasa , Tsuboi Yoshiyuki , Imai Takao , Sumino Rhyuji , Morimoto Toshifumi , Dubner Ronald , Ren Ke 
Published: December 2017

Studies at spinal levels indicate that peripheral tissue or nerve injury induces a state of hyperexcitability of spinal dorsal horn neurons that participates in the development of persistent pain and hyperalgesia. It has not been demonstrated that persistent injury in the orofacial region leads to a similar state of central hyperexcitability in the trigeminal system. The purpose of the present study was to conduct a parametric analysis of the response properties of nociceptive and nonnociceptive neurons in trigeminal nucleus caudalis (medullary dorsal horn, MDH) in a rat model of persistent orofacial inflammation. Neurons were recorded extracellularly and classified as low-threshold mechanoreceptive (LTM, n = 49), wide dynamic range (WDR, n = 82), and nociceptive-specific (NS, n = 11) neurons according to their response properties to mechanical stimuli applied to their cutaneous receptive fields (RFs). The inflammation was induced 24 h before the recordings by injecting complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) capsule or the perioral (PO) skin. The mean areas of the high-threshold RFs of WDR neurons in TMJ (8.66 ± 0.61 cm2, n = 25) and PO (5.61 ± 2.07 cm2, n = 25) inflamed rats were significantly larger than those in naive rats (1.10 ± 0.16 cm2, n = 32). The mean RF size in TMJ-inflamed rats also was significantly larger than that in PO-inflamed rats ( P < 0.01). Furthermore the mean area of the RFs of NS neurons (3.74 ± 1.44 cm2, n = 5) was significantly larger in TMJ inflamed rats as compared with naive rats (0.4 ± 0.09 cm2, n = 3) ( P < 0.05). The background activity in the TMJ- and PO-inflamed rats was generally greater in WDR and NS neurons, but less in LTM neurons, when compared with naive rats. The responses of WDR neurons to noxious mechanical stimuli were increased significantly in TMJ-inflamed rats ( P < 0.05) as compared with naive rats. WDR neuronal responses to mechanical stimulation also were increased in PO-inflamed rats but to a lesser extent than in TMJ-inflamed rats. The injection of CFA into the TMJ or PO skin resulted in reduced responses of LTM neurons to mechanical stimuli. The responses of MDH nociceptive neurons to 48–55°C heating were greater in inflamed rats as compared with naive rats. A subpopulation of WDR neurons recorded from TMJ ( n = 4 of 10)- or PO ( n = 3 of 13)-injected rats responded to cooling in addition to heating of the RFs but did not grade their responses with changes in stimulus intensity. These results indicate that persistent orofacial inflammation produced hyperexcitability of MDH nociceptive neurons. TMJ inflammation resulted in more robust changes in MDH nociceptive neurons as compared with PO inflammation, consistent with previous studies of increased inflammation, increased MDH Fos-protein expression, and increased MDH preprodynorphin mRNA expression in this deep tissue orofacial model of pain and hyperalgesia. The inflammation-induced MDH hyperexcitability may contribute to mechanisms of persistent pain associated with orofacial deep tissue painful conditions.