Vanilloid receptor 1-like receptor-immunoreactive primary sensory neurons in the rat trigeminal nervous system

Immunohistochemistry for vanilloid receptor 1-like receptor (VRL-1), a candidate transducer for high-threshold noxious heat, was performed on rat trigeminal primary sensory neurons. The immunoreactivity was detected in 14% of the trigeminal ganglion cell bodies, while the neurons in the mesencephalic trigeminal tract nucleus were almost devoid of it (0.5%). The immunoreactive neurons in the trigeminal ganglion were mostly of medium to large size (mean+/-S.D. of 956+/-376microm(2)). Nerve bundles in the tooth pulp, periodontal ligament, facial skin and oral mucosa contained VRL-1-positive smooth nerve fibers. The immunoreactivity could not be traced to the isolated nerve fibers, except in the tooth pulp. In the brainstem trigeminal nuclear complex, a notable concentration of the immunoreactivity was seen in laminae I and II of the medullary dorsal horn. Thirty-seven per cent of the trigeminal ganglion neurons retrogradely labeled from the tooth pulp exhibited VRL-1 immunoreactivity, while the immunoreactivity was detected in only 9% of those labeled from the skin. Co-expression of calcitonin gene-related peptide was common among the VRL-1-immunoreactive tooth pulp neurons (45%) and cutaneous neurons (25%). Moreover, as many as 41% of the VRL-1-immunoreactive tooth pulp neurons co-expressed parvalbumin immunoreactivity. Parvalbumin immunoreactivity was never detected in the VRL-1-immunoreactive cutaneous neurons.From the findings of the present study, we propose that large primary neurons responding to high-threshold noxious heat are abundant in the tooth pulp, but not in the facial skin.     

Structural and functional adaptation of the pulpal nerve fibers in the rat incisor

Special fine structure of the pulpal nerve fibers adapted to the continuously growing incisor was studied on 20 rats (25-d-old-males) electron microscopically and was compared with that of the molars of limited growth. The incisal pulp was innervated by 2 kinds of the nerve fibers derived from the cervical sympathetic and the trigeminal ganglia: polyaxonal unmyelinated and monoaxonal myelinated. In the apical pulp, however, the pulpal nerve fibers were unmyelinated, showing 3 different profiles in the fine structure: 1. polyaxonal, 2. polyaxonal with dial plate-like profile and 3. monoaxonal. The monoaxonal unmyelinated fiber reflected the transverse profile of the unmyelinated part of the myelinated axon derived from the trigeminal ganglion. It can be concluded that the pulpal nerve fibers derived from the trigeminal ganglion maintain the immatured nature in the apical proliferating pulp to adapt to the continuous growth of the incisor.     

Immunohistochemical Localization of SNARE Proteins in Dental Pulp and Periodontal Ligament of the Rat Incisor

Distribution of three soluble N‐ethylmaleimide‐sensitive fusion protein attachment protein receptor (SNARE) proteins, syntaxin‐1, synaptosomal‐associated protein of 25 kDa (SNAP‐25), and vesicle‐associated membrane protein‐2 (VAMP‐2), was examined in dental pulp and periodontal ligament of the rat incisor. In the trigeminal ganglion, syntaxin‐1 and SNAP‐25 immunoreactivity was predominately detected in medium‐ to large‐sized neurons. Most syntaxin‐1 immunoreactive neurons expressed SNAP‐25. In contrast, VAMP‐2 was localized in small‐ to medium‐sized neurons and in slender‐shaped cells surrounding SNAP‐25‐immunopositive neurons. When the inferior alveolar nerve, one of the mandibular nerve branches innervating the dental pulp and periodontal ligament, was ligated, SNARE proteins accumulated at the site proximal to the ligation. In the incisor dental pulp, all nerve fibers displayed immunoreactivity for syntaxin‐1, SNAP‐25, and VAMP‐2. In the periodontal ligament of the incisor, almost all nerve fibers displayed both syntaxin‐1 and SNAP‐25 immunoreactivity, but lacked VAMP‐2 immunoreactivity. SNAP‐25 protein expression was localized around the vesicle membranes at the axon terminal of the periodontal mechanoreceptors. These present data suggest that these three SNARE proteins are synthesized at the trigeminal ganglion, transported centrally and peripherally, and expressed in sensory endings where apparent synapses are not present. Because those proteins participate in docking and exocytosis of synapse vesicles in the central nervous system, they might also contribute to vesicle exocytosis at receptive fields where apparent synapses are not present. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Electron microscopic demonstration of horseradish peroxidase-tetramethylbenzidine reaction product as a method for identifying sensory nerve fibers in the rat tooth pulp

The purpose of the present investigation was to determine if the horseradish peroxidase could be used as a method for labeling sensory nerve fibers (specifically, tooth pulp afferents) for detailed ultrastructural analyses. HRP injected into the trigeminal ganglion of adult rats was taken up by ganglion cell bodies and transported anterogradely to their peripheral endings in the dental tissues. Following perfusion-fixation, the teeth were decalcified in EDTA, sectioned, reacted for HRP activity according to the tetramethylbenzidine (TMB) technique, and processed for electron microscopy. The HRP-TMB reaction product was clearly visible within most of the axons in the dental pulp, appearing as conspicuous, rectangular shaped aggregates of fine rods or needles.     

Alteration in the expression of heat shock protein (Hsp) 25-immunoreactivity in the dental pulp of rat molars following tooth replantation.

The regeneration process of dental pulp following tooth replantation in rat molars was investigated by immunocytochemistry for heat shock protein (Hsp) 25 and protein gene product 9.5 (PGP 9.5). In control teeth at postnatal 4 weeks, the odontoblasts showed intense Hsp 25-immunoreactivity in the coronal dental pulp, but little or no immunoreactivity in the root and floor pulp. In contrast, the Hsp 25-negative odontoblasts in the latter areas displayed immunoreactivity for PGP 9.5. Tooth replantation caused loss of Hsp 25- and PGP 9.5-immunoreactions in the dental pulp during postoperative days 1-3. At postoperative day 5, plump cells with clear nucleoli and several fine processes--presumably newly differentiated odontoblasts--at the pulp-dentin border became immunopositive for Hsp 25. These data suggest that the expression of Hsp 25- and PGP 9.5-immunoreactivity reflects the status of differentiation of the odontoblasts. Furthermore, some pulpal nerve fibers as well as the Schwann cells in the dental pulp, ordinarily negative in Hsp 25-immunoreaction, acquired their immunoreactivity by postoperative day 5, but lost it thereafter, suggesting the involvement of Hsp 25 in the regeneration of pulpal nerve fibers. In the case of bone-like tissue formation in the pulp space, on the other hand, no Hsp 25-immunoreactive odontoblasts were recognized in the pulp-dentin border. Thus, the alignment of Hsp 25-immunopositive odontoblasts along the pulp-dentin border indicates a decisive factor for inducing the reparative dentin formation after tooth replantation.     

Time-dependent differences in the increase in GAP-43 expression in dorsal root ganglion cells after peripheral axotomy.

Peripheral axotomy of primary afferent neurons results in the up-regulation of the growth-associated phosphoprotein GAP-43, by dorsal root ganglion cells. We have studied the temporal sequence of GAP-43 expression in those dorsal root ganglion neurons with unmyelinated axons (the small dark cells) and in those with myelinated axons (the large light cells) after sciatic nerve section in the adult rat. Immunoreactivity for the RT 97 neurofilament epitope, which is detectable only in large light dorsal root ganglion cells, was used to differentiate the two types of dorsal root ganglion cell. Within two days of a sciatic nerve section the number of GAP-43-immunoreactive profiles in the ipsilateral ganglion had increased five-fold and this increase persisted for 80 days post-section. While 50% of the small numbers of GAP-43-positive cells in control ganglia were RT 97 positive, only 8% of the large number of GAP-43-immunoreactive cells four days post-section, were RT 97 positive. By 14 days the number of RT 97-positive/GAP-43-positive cells had increased to 29%. This was paralleled by an increase in GAP-43 immunoreactivity in large diameter profiles at 14 days. The signals that alter GAP-43 expression in unmyelinated (small, RT 97 -ve) and myelinated (large, RT 97 +ve) afferents after peripheral nerve injury appear to operate with different time-courses.     

Morphological studies of bradykinin-treatments on the rat trigeminal sensory neuron

Subcutaneous injections of bradykinin to the rat trigeminal region over 4 days produced a significant increase in the number of mitochondria in the small trigeminal ganglion cells and the central terminals of unmyelinated fibers in the spinal trigeminal nucleus. In the large trigeminal ganglion cells, no significant change in the number of mitochondria was observed. These results seem to demonstrate that bradykinin stimulates unmyelinated nerve and increases its energy consumption.     

Expression of the 5-HT1B receptor by subtypes of rat trigeminal ganglion cells

The type of trigeminal ganglion cells that express 5-HT1B receptors has not been well characterized, despite the fact that these receptors are important targets for anti-migraine drugs. We have therefore used combined in situ hybridization and immunofluorescence to examine the expression of 5-HT1B receptor messenger RNA in identified subpopulations of rat trigeminal ganglion cells. 5-HT1B-expressing cells accounted for 15% of all trigeminal ganglion cells, were medium sized, and showed immunoreactivity for either 200,000 mol. wt neurofilament, calcitonin gene-related peptide, or nerve growth factor receptor (trkA). In contrast few 5-HT1B cells showed immunoreactivity for substance P or binding of the lectin Griffonia simplicifolia IB4. Our results are consistent with 5-HT1B receptors acting to control the release of calcitonin gene-related peptide from trigeminal neurons with finely myelinated axons. 5-HT1B receptor agonists may reduce neurogenic vasodilation by activating such receptors. However many nociceptive trigeminal neurons, including the substance P and IB4-binding populations, do not express the 5-HT1B receptor.     

Somatostatin, galanin and peptide histidine isoleucine in the newborn and adult human trigeminal ganglion and spinal nucleus: Immunohistochemistry, neuronal morphometry and colocalization with substance P

By means of indirect immunofluorescence the neuropeptides somatostatin, galanin and peptide histidine isoleucine were localized in cell bodies, nerve fibres and terminal-like elements in the ganglion and spinal nucleus of the human trigeminal nerve in perinatal and adult ages. No immunoreactivity to vasoactive intestinal polypeptide was observed. In the gasserian ganglion somatostatin-, galanin- and peptide histidine isoleucine-containing neurons and nerve fibres occurred frequently in pre- and full-term newborns, but were scarce to absent in adults. Somatostatin- and galanin-positive pericellular basket-like structures around non-immunoreactive perikarya were observed in newborn specimens. Immunoreactivity to somatostatin, galanin and peptide histidine isoleucine labelled nerve fibers and punctate and felt-like nerve terminals in the pars interpolaris and subnucleus caudalis of the spinal trigeminal nucleus, with immunostaining and distribution patterns characteristic for each peptide. In addition, somatostatin-containing neuronal cell bodies frequently were detected. At variance with those containing somatostatin, the number of galanin- and peptide histidine isoleucine-like immunoreactive elements were dramatically reduced in the adult tissue compared to the newborn one. Double immunostaining revealed that each of the three peptides partially colocalizes with substance P, the degree of coexistence being very low for somatostatin/substance P and high for galanin/substance P and peptide histidine isoleucine/substance P both in the gasserian ganglion and in the spinal nucleus. The results obtained suggest that somatostatin, galanin and peptide histidine isoleucine may play functional roles in primary sensory neurons and at the first synaptic level of the human trigeminal sensory system.     

Sympathetic nerve fibers sprout into rat odontoblast layer, but not into dentinal tubules, in response to cavity preparation

This study was designed to determine if sympathetic nerve fibers exist in dentinal tubules in rat normal dental pulp, and if they sprout into the dentinal tubules in response to artificial cavity preparation in dentin. Sympathetic nerve fibers in rat molar dental pulp were labeled using an anterograde axonal transport technique involving injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the superior cervical ganglion (SCG). They were then observed using light and electron microscopes. In normal dental pulp (control), scattered WGA-HRP reaction products were observed in unmyelinated nerve endings in the odontoblast layer and subodontoblastic region. In injured pulp 3 weeks after cavity preparation, reaction products were about 1.8-times more plentiful in the above areas (versus control pulp). However, no labeled nerve fibers were observed in the dentinal tubules in either control or injured dental pulp. These results indicate that although sympathetic nerve fibers do indeed sprout in rat dental pulp in response to cavity preparation, they do not penetrate into the dentinal tubules in which postganglionic nerve endings derived from the SCG were not originally present.     

Involvement of galanin receptors 1 and 2 in the modulation of mouse vagal afferent mechanosensitivity

It is established that the gut peptide galanin reduces neuronal excitability via galanin receptor subtypes GALR1 and GALR3 and increases excitability via subtype GALR2. We have previously shown that galanin potently reduces mechanosensitivity in the majority of gastro-oesophageal vagal afferents, and potentiates sensitivity in a minority. These actions may have implications for therapeutic inhibition of gut afferent signalling. Here we investigated which galanin receptors are likely to mediate these effects. We performed quantitative RT-PCR on RNA from vagal (nodose) sensory ganglia, which indicated that all three GALR subtypes were expressed at similar levels. The responses of mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated before and during application of galanin receptor ligands to their peripheral endings. Two types of vagal afferents were tested: tension receptors, which respond to circumferential tension, and mucosal receptors which respond only to mucosal stroking. Galanin induced potent inhibition of mechanosensitivity in both types of afferents. This effect was totally lost in mice with targeted deletion of Galr1 . The GALR1/2 agonist AR-M961 caused inhibition of mechanosensitivity in Galr1 +/+ mice, but this was reversed to potentiation in Galr1 −/− mice, indicating a minor role for GALR2 in potentiation of vagal afferents. We observed no functional evidence of GALR3 involvement, despite its expression in nodose ganglia. The current study highlights the complex actions of galanin at different receptor subtypes exhibiting parallels with the function of galanin in other systems.     

Light and electron microscopic analysis of the somata and parent axons innervating the rat upper molar and lower incisor pulp

The morphology of intradental nerve fibers of permanent teeth and of continuously growing rodent incisors has been studied in detail but little information is available on the parent axons that give rise to these fibers. Here we examined the axons and somata of trigeminal neurons that innervate the rat upper molar and lower incisor pulp using tracing with horseradish peroxidase and light and electron microscopic analysis. The majority (∼80%) of the parent axons in the proximal root of the trigeminal ganglion that innervated either molar or incisor pulp were small myelinated fibers (<20 μm² cross-sectional area). The remaining ∼20% of the fibers were almost exclusively large myelinated for the molar pulp and unmyelinated for the incisor pulp. The majority of neuronal somata in the trigeminal ganglion that innervated either molar (48%) or incisor pulp (62%) were medium in size (300–600 μm² cross-sectional area). Large somata (>600 μm²) constituted 34% and 20% of the trigeminal neurons innervating molar and incisor pulp, respectively, while small somata (<300 μm²) constituted 17% of the molar and 18% of the incisor neurons. The present study revealed that the morphology of parent axons of dental primary sensory neurons may differ from that of their intradental branches, and also suggests that the nerve fiber function may be carried out differently in the molar and incisor pulp in the rat.     

Ultrastructural localization of increased neuropeptide immunoreactivity in the axons and cells of the gracile nucleus following chronic constriction injury of the sciatic nerve.

Neuropeptide plasticity in the gracile nucleus is thought to play a role in the development of neuropathic pain following nerve injury. Two weeks after chronic constriction injury of adult rat sciatic nerve, galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities were increased in fibers and cells in the gracile nucleus ipsilateral to injury. At the electron microscopic level, this increased neuropeptide immunoreactivity was localized in myelinated axons, boutons, dendrites, neurons and glial cells. Galanin-, neuropeptide Y- and calcitonin gene-related peptide-immunoreactive boutons were frequently presynaptic to dendrites of both immunoreactive and non-immunoreactive neurons. However, no neuropeptide Y, galanin and calcitonin gene-related peptide messenger RNA was detected in the injured side gracile nuclei by in situ hybridization. These results show that partial nerve injury to the sciatic nerve induces increases in the content of galanin, neuropeptide Y and calcitonin gene-related peptide immunoreactivities in synaptic terminals within the gracile nucleus, which suggests that there may be increased release of these neuropeptides following sensory or spontaneous stimulation of large-diameter primary afferents following partial nerve injury, perhaps one mechanism involved in neuropathic pain. We also show an apparent transfer of these neuropeptides to the cells of the gracile nucleus, both neurons and glial cells, an intriguing phenomenon of unknown functional significance.     

Target finding of pain nerve fibers: neural growth mechanisms in the tooth pulp

The tooth pulp has a dense sensory innervation which, upon stimulation, conveys sensory signals perceived as pain. This innervation, which originates from the trigeminal ganglion, is established through a series of regulated steps during development, and represents an interesting example of tissue targeting by pain-specific nerves. We have investigated various potentially neurotrophic and neurorepulsive influences during this process. The dental papilla/pulp appears to secrete neurite growth inhibitory molecular factors at early stages, which prevent nerve fibers from entering the tissue at what appears to be inappropriate timepoints. Later, a shift from repulsive to attractive factors apparently takes place, and nerve fibers then enter the tooth. When nerve fibers have invaded the dental mesenchyme, a complicated interplay of secreted and membrane-bound factors probably directs the nerve terminals to appropriate sites. Laminin-8 (alpha4beta1gamma1, Lm-411), which is produced by pulpal cells, emerges as an important candidate molecule in this context. Insights into the interactions between the dental pulp nerve fibers and their environment may become important in the search for novel ways to ameliorate pain in the tooth, as well as at other sites.     

Sub-populations of smaller diameter trigeminal primary afferent neurons defined by expression of calcitonin gene-related peptide and the cell surface oligosaccharide recognized by monoclonal antibody LA4.

Summary Immunocytochemistry has been used to examine the trigeminal ganglion cell populations in the rat which express calcitonin gene-related peptide (CGRP) and the oligosaccharide antigen recognized by the monoclonal antibody LA4. Calcitonin gene-related peptide and LA4 identify two large but mainly separate populations of trigeminal ganglion cells. Depending on the method of assessment used, CGRP-immunoreactive cells represent 29–37% of trigeminal ganglion cells while LA4 labels 26–40% of the cells, but with only 8% overlap between the two populations. Both CGRP and LA4 label predominantly small diameter cells (mean diameters 23 m and 25 m respectively) but with CGRP cells exhibiting a greater range of diameters than LA4 cells. The cell sizes indicate that small diameter CGRP-immunoreactive cells and most LA4-immunoreactive cells are likely to have unmyelinated axons, and together the two populations can account for the great majority of unmyelinated trigeminal primary afferent neurons. Centrally, CGRP and LA4 show distinct patterns of staining. Thus although both antigens are found in lamina II of subnucleus caudalis of the spinal trigeminal nucleus, CGRP is most abundant in lamina I and lamina II outer while LA4 irnmunoreactivity is most dense in lamina II inner. In addition CGRP-, but not LA4-, immunoreactive fibres occur in the magnocellular portion of caudalis. Previous studies have show that in rat dorsal root ganglion cells CGRP coexists with most other known neuropeptides and can therefore be used as a general marker for peptide-containing primary afferents. In contrast LA4 labels a cell population which is probably largely identical to that identified by the presence of fluoride resistant acid phosphatase or by the binding of lectins such as Griffonia simplidfolia isolectin B4 and this population does not contain neuropeptides. Our results thus provide further evidence that unmyelinated primary afferents can be divided into peptide and non-peptide containing subpopulations and that these populations innervate distinct regions of laminae I and II.     

Distribution of TRPV1- and TRPV2-immunoreactive afferent nerve endings in rat trachea

Nociception in the trachea is important for respiratory modulation. We investigated the distribution, neurochemical characteristics, and origin of nerve endings with immunoreactivity for candidate sensor channels, TRPV1 and TRPV2, in rat trachea. In the epithelial layer, the intraepithelial nerve endings and dense subepithelial network of nerve fibers were immunoreactive for TRPV1. In contrast, TRPV2 immunoreactivity was observed mainly in nerve fibers of the tracheal submucosal layer and in several intrinsic ganglion cells in the peritracheal plexus. Double immunostaining revealed that some TRPV1-immunoreactive nerve fibers were also immunoreactive for substance P or calcitonin gene-related peptide, but neither neuropeptide colocalized with TRPV2. Injection of the retrograde tracer, fast blue, into the tracheal wall near the thoracic inlet demonstrated labeled neurons in the jugular, nodose, and dorsal root ganglia at segmental levels of C2-C8. In the jugular and nodose ganglia, 59.3% (70/118) and 10.7% (17/159), respectively, of fast blue-labeled neurons were immunoreactive for TRPV1, compared to 8.8% (8/91) and 2.6% (5/191) for TRPV2-immunoreactive. Our results indicate that TRPV1-immunoreactive nerve endings are important for tracheal nociception, and the different expression patterns of TRPV1 and TRPV2 with neuropeptides may reflect different subpopulations of sensory neurons.     

The cellular localization of preprotachykinin A messenger RNA in the bovine nervous system

The cellular distribution of preprotachykinin A messenger RNA in the bovine nervous system was investigated by in situ hybridization and its tissue distribution by Northern and dot blotting. The latter results were compared with the levels of substance P-like immunoreactivity as determined by radio-immunoassay. The highest levels of preprotachykinin A messenger RNA were found in striatum and trigeminal ganglion, medium levels in retina and lower levels in hypothalamus, spinal cord, pituitary gland and adrenal medulla. The cellular localization of preprotachykinin A messenger RNA was obtained in striatum and trigeminal ganglion using either single-stranded DNA or complementary RNA probes labelled with 32P, 35S or 3H. Specific labelling of small trigeminal ganglion neurones and of medium-sized striatal nerve cells was observed with probes in the anti-messenger RNA sense orientation. Only background labelling was obtained with probes in the messenger RNA sense orientation. The technique was further validated by the demonstration that the same cells in the trigeminal ganglion were labelled by both in situ hybridization and immunohistochemistry. The present findings allow an unambiguous identification of the cellular sites of synthesis of preprotachykinin A messenger RNA; in situ hybridization should also prove a useful technique for investigating the regulation of neuropeptide biosynthesis at the cellular level.     

Immunoelectron microscopic observation of calcitonin gene-related peptide (CGRP)-positive nerves in the dental pulp of rat molars.

The ultrastructure of nerves containing immunoreactivity for calcitonin gene-related peptide (CGRP) was investigated in the dental pulp of rat molars. The immunoreactivity was recognized predominantly in unmyelinated nerve fibers, and sparsely in a few myelinated fibers. It was localized throughout the axoplasm, as well as in the large cored vesicles. Small clear vesicles and mitochondria were free of the immunoreaction. The CGRP-immunoreactive nerves were frequently observed to terminate, being devoid of Schwann cell investment, in the vicinity of blood vessels in the coronal pulp, suggesting that CGRP may be involved in the regulation of pulpal blood flow. Moreover, CGRP-immunoreactive axon terminals containing numerous small clear vesicles, a few large cored vesicles and mitochondria were recognized in contact with the cell bodies of odontoblasts and their processes in the dentinal tubules. Although specialized synaptic ultrastructures were not recognizable, a functional association of CGRP nerves and odontoblasts was suggested. Thus, CGRP in the dental pulp appears to have multiple functions, including vascular regulation and sensory transduction.     

trkA modulation of developing somatosensory neurons in oro-facial tissues: tooth pulp fibers are absent in trkA knockout mice

To investigate the nerve growth factor requirement of developing oro-facial somatosensory afferents, we have studied the survival of sensory fibers subserving nociception, mechanoreception or proprioception in receptor tyrosine kinase (trkA) knockout mice using immunohistochemistry. trkA receptor null mutant mice lack nerve fibers in tooth pulp, including sympathetic fibers, and showed only sparse innervation of the periodontal ligament. Ruffini endings were formed definitively in the periodontal ligament of the trkA knockout mice, although calcitonin gene-related peptide- and substance P-immunoreactive fibers were reduced in number or had disappeared completely. trkA gene deletion had also no obvious effect on the formation of Meissner corpuscles in the palate. In the vibrissal follicle, however, some mechanoreceptive afferents were sensitive for trkA gene deletion, confirming a previous report [Fundin et al. (1997) Dev. Biol. 190, 94-116]. Moreover, calretinin-positive fibers innervating longitudinal lanceolate endings were completely lost in trkA knockout mice, as were the calretinin-containing parent cells in the trigeminal ganglion.These results indicate that trkA is indispensable for developing nociceptive neurons innervating oral tissues, but not for developing mechanoreceptive neurons innervating oral tissues (Ruffini endings and Meissner corpuscles), and that calretinin-containing, trkA dependent neurons in the trigeminal ganglion normally participate in mechanoreception through longitudinal lanceolate endings of the vibrissal follicle.