The development of myelinated nociceptors is dependent upon trks in the trigeminal ganglion.
Cell size of primary sensory neurons and distribution patterns of neurons that are immunopositive (ip) for VRL-1, a newly cloned capsaicin-receptor homologue, were examined in trigeminal ganglia (TGs) of knockout mice for trkA, trkB or trkC to determine the developmental dependency of myelinated nociceptors on expression of the genes. The number of TG neurons was strongly decreased in the knockout mice as compared to wildtype and heterozygous mice (82%, 39%, and 48% reduction for trkA, trkB and trkC, respectively). The absence of trkA and trkC reduced the number of TG neurons in all cell-size ranges. The number of medium-sized and large TG neurons was decreased in trkB-knockout mice, whereas that of small TG neurons was barely affected by trkB deficiency. TG contained abundant VRL-1-ip neurons in wildtype and heterozygous mice; 9% of TG neurons exhibited immunopositivity. In trkA-knockout mice, VRL-1-ip neurons almost disappeared (1% of TG neurons were VRL-1-ip). However, 13% and 9% of TG neurons in trkB- and trkC-knockout mice, respectively, were immunostained for the ion channel protein. In trkC-knockout mice, the proportion of large VRL-1-ip neurons decreased whereas that of small and medium-sized VRL-1-ip neurons increased. In addition, immunohistochemistry of the protein gene product 9.5 (PGP 9.5) demonstrated that trkA deficiency caused a marked reduction of varicose endings in the epithelium of the palatal mucosa. Loss of trkC diminished the number of PGP 9.5-ip varicose fibers in the deep layer of mucosal connective tissue of the palate. In tooth pulp, PGP 9.5-ip nerve fibers were absent in trkA-knockout mice but abundant in trkB- and trkC-knockout mice. The present study suggests that the development of myelinated nociceptors is dependent on trkA and trkC but not on trkB.
Ichikawa
Hiroyuki
H
Department of Oral Function and Anatomy, Biodental Research Center, Okayama University Graduate School of Medicine and Dentistry, Okayama 700, Japan. hiroichi@md.okayama-u.ac.jp
Matsuo
Saburo
S
Silos-Santiago
Inmaculada
I
Jacquin
Mark F
MF
Sugimoto
Tomosada
T
D000818:Animals; D002452:Cell Count; D048429:Cell Size; D003782:Dental Pulp / Q000294:innervation; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010159:Palate / Q000294:innervation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D050916:TRPV Cation Channels; D012668:Trigeminal Ganglion / Q000378:metabolism*
D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D020794:Receptor Protein-Tyrosine Kinases