Contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus produced by acute injury to the masseter muscle during persistent temporomandibular joint inflammation in rats

We investigated the contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus (VSP) following acute masseter muscle injury in male rats with or without temporomandibular joint (TMJ) inflammation persisting for 7 days. TMJ inflammation was evoked by an injection of complete Freund's adjuvant (CFA). Two hours after formalin injection into the masseter muscle produced Fos-like immunoreactivity (Fos-LI) in several regions of the VSP and upper cervical spinal cord (C2), such as ventrolateral (vl) area of the trigeminal subnucleus caudalis (Vc)/subnucleus interpolaris (Vi) transition (vl-Vi/Vc), paratrigeminal nucleus (dPa5), middle portion of the Vc (mid-Vc) and Vc/C2 transition (Vc/C2) regions in both groups. Significant increases in the number of Fos-LI were observed in these areas in CFA group compared with non-CFA group. TMJ inflammation alone did not induce a significant level of Fos-LI in the VSP. In order to assess the effect of antagonizing 5-HT2A or 5-HT3 receptors on formalin-induced Fos-LI, rats were pre-treated with local (masseter muscle) administration of ketanserin or tropisetron (0.01, 0.1 mg/rat) 20 min prior to formalin injection. In CFA group, these antagonists given locally reduced the Fos-LI response in the laminae I-II at the mid-Vc and Vc/C2 regions. These antagonists reduced the Fos-LI response in the dPa5, but not in the vl-Vi/Vc region. The Fos-LI response was not affected by i.v. administration of ketanserin (0.01, 0.1 mg/rat) or tropisetron (0.01 mg/rat). In non-CFA group, these antagonists given locally did not reduce the Fos-LI response. These results suggest that peripheral 5-HT2A and 5-HT3 receptors contribute to nociceptive processing in the masseter muscle in TMJ inflammatory conditions.