Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats.

In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and gamma-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABA(A) receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABA(A) receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin-NTS, lingual muscle-NTS and lingual muscle-Pa5-NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures.

Modulation of trigeminal spinal subnucleus caudalis neuronal activity following regeneration of transected inferior alveolar nerve in rats.

Modulation of trigeminal spinal subnucleus caudalis neuronal activity following regeneration of transected inferior alveolar nerve in rats. To clarify the neuronal mechanisms of abnormal pain in the face innervated by the regenerated inferior alveolar nerve (IAN), nocifensive behavior, trigeminal ganglion neuronal labeling following Fluorogold (FG) injection into the mental skin, and trigeminal spinal subnucleus caudalis (Vc) neuronal properties were examined in rats with IAN transection. The mechanical escape threshold was significantly higher at 3 days and lower at 14 days after IAN transection, whereas head withdrawal latency to heat was significantly longer at 3, 14, and 60 days after IAN transection. The number of FG-labeled ganglion neurons was significantly reduced at 3 days after IAN transection but increased at 14 and 60 days. The number of wide dynamic range (WDR) neurons with background (BG) activity was significantly higher at 14 and 60 days after IAN transection compared with naïve rats, and the number of WDR and low-threshold mechanoreceptive (LTM) neurons with irregularly bursting BG activity was increased at these two time points. Mechanically evoked responses were significantly larger in WDR and LTM neurons 14 days after IAN transection compared with naïve rats. Heat- and cold-evoked responses in WDR neurons were significantly lower at 14 days after transection compared with naïve rats. Mechanoreceptive fields were also significantly larger in WDR and LTM neurons at 14 and 60 days after IAN transection. These findings suggest that these alterations may be involved in the development of mechanical allodynia in the cutaneous region innervated by the regenerated IAN.

Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis and upper cervical cord following capsaicin injection into oral and craniofacial regions in rats.

To define the somatotopic arrangement of neurons in the trigeminal spinal subnucleus caudalis and upper cervical cord activated by acute noxious stimulation of various orofacial sites, pERK expression was analyzed in these neurons. After capsaicin injection into the tongue, lower gum, upper and lower lips, or mental region, pERK-like immunoreactive (pERK-LI) cells were distributed mainly in the dorsal half of the trigeminal spinal nucleus interporalis (Vi) and caudalis (Vc) transition zone (Vi/Vc zone), middle Vc, and Vc and upper cervical cord transition zone (Vc/C2 zone). pERK-LI cells were distributed throughout the dorsal to ventral portion of the Vi/Vc zone, middle Vc, and Vc/C2 zone following capsaicin injection into the anterior hard palate, upper gum, buccal mucosa, or vibrissal pad and in the ventral portion of the Vi/Vc zone, middle Vc, and Vc/C2 zone following snout, ophthalmic, or ocular injection of capsaicin. The rostrocaudal distribution area of pERK-LI cells was more extensive from the Vi/Vc zone to the Vc/C2 zone after intraoral injection than that after facial injection, and the rostrocaudal distribution of pERK-LI cells from the Vi/Vc zone to the Vc/C2 zone had a somatotopic arrangement, with the snout being represented most rostrally and ophthalmic, ocular, or mental regions represented most caudally. These findings suggest that the pERK-LI cells expressed from the Vi/Vc zone to the Vc/C2 zone following injection of capsaicin in facial and intraoral structures may be differentially involved in pain perception in facial and intraoral sites.

Organization of cortical processing for facial movements during licking in cats.

We proposed that cortical organization for the execution of adequate licking in cats was processed under the control of two kinds of affiliated groups for face and jaw & tongue movements (Hiraba H, Sato T. 2005A. Cerebral control of face, jaw, and tongue movements in awake cats: Changes in regional cerebral blood flow during lateral feeding Somatosens Mot Res 22:307-317). We assumed the cortical organization for face movements from changes in MRN (mastication-related neuron) activities recorded at area M (motor cortex) and orofacial behaviors after the lesion in the facial SI (facial region in the primary somatosensory cortex). Although we showed the relationship between facial SI (area 3b) and area M (area 4delta), the property of area C (area 3a) was not fully described. The aim of this present study is to investigate the functional role of area C (the anterior part of the coronal sulcus) that transfers somatosensory information in facial SI to area M, as shown in a previous paper (Hiraba H. 2004. The function of sensory information from the first somatosensory cortex for facial movements during ingestion in cats Somatosens Mot Res 21:87-97). We examined the properties of MRNs in area C and changes in orofacial behaviors after the area C or area M lesion. MRNs in area C had in common RFs in the lingual, perioral, and mandibular parts, and activity patterns of MRNs showed both post- and pre-movement types. Furthermore, cats with the area C lesion showed similar disorders to cats with the area M lesion, such as the dropping of food from the contralateral mouth, prolongation of the period of ingestion and mastication, and so on. From these results, we believe firmly the organization of unilateral cortical processing in facial SI, area C, and area M for face movements during licking.