journal article
Sep 01, 2025
Immunohistochemical Analysis of Maxillary Nerve Distribution in Rats
Abstract
Objective
Previous studies of nerve distribution in the orofacial complex have focused primarily on the anatomic courses of nerve fibers and have rarely addressed the density of nerve distribution. The nerve distribution in the mandible was described in only one report which showed an increase in nerve distribution density moving from the alveolar crest toward the inferior alveolar nerve. However, no previous reports have focused on the nerve distribution density in the maxilla.
Methods
In this study involving 6 Wistar rats, tissue samples from the maxillary molar region were obtained and sectioned for staining and analysis. All nerves including nociceptive nerves in 5 regions of the maxilla samples, ranging from the alveolar crest to the superior alveolar nerve, were immunohistochemically stained with antibodies to protein gene product (PGP) and calcitonin gene-related peptide (CGRP) to identify and measure the vertical and horizontal nerve distribution densities in the 5 regions under an optical microscope. We also determined the ratio of nociceptive (CGRP-positive) nerves to all (PGP-positive) nerves.
Results
The densities of both PGP- and CGRP-positive nerves increased vertically from the alveolar crest to the superior alveolar nerve and horizontally from the periosteal side to the periodontal ligament side within the maxilla. The ratio of CGRP- to PGP-positive nerves was on average greater than 80%.
Conclusion
These findings were consistent with those of the previous report on mandibular nerve distribution. However, our results suggest that the overall nerve distribution density in the maxilla is approximately one-third of that in the mandible. The results of this study, which report the nerve distribution density in the posterior maxilla, may support future research on pain and local anesthesia.
Previous studies of nerve distribution in the orofacial complex have focused primarily on the anatomic courses of nerve fibers and have rarely addressed the density of nerve distribution. The nerve distribution in the mandible was described in only one report which showed an increase in nerve distribution density moving from the alveolar crest toward the inferior alveolar nerve. However, no previous reports have focused on the nerve distribution density in the maxilla.
Methods
In this study involving 6 Wistar rats, tissue samples from the maxillary molar region were obtained and sectioned for staining and analysis. All nerves including nociceptive nerves in 5 regions of the maxilla samples, ranging from the alveolar crest to the superior alveolar nerve, were immunohistochemically stained with antibodies to protein gene product (PGP) and calcitonin gene-related peptide (CGRP) to identify and measure the vertical and horizontal nerve distribution densities in the 5 regions under an optical microscope. We also determined the ratio of nociceptive (CGRP-positive) nerves to all (PGP-positive) nerves.
Results
The densities of both PGP- and CGRP-positive nerves increased vertically from the alveolar crest to the superior alveolar nerve and horizontally from the periosteal side to the periodontal ligament side within the maxilla. The ratio of CGRP- to PGP-positive nerves was on average greater than 80%.
Conclusion
These findings were consistent with those of the previous report on mandibular nerve distribution. However, our results suggest that the overall nerve distribution density in the maxilla is approximately one-third of that in the mandible. The results of this study, which report the nerve distribution density in the posterior maxilla, may support future research on pain and local anesthesia.
Topics
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References
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Sorokivskyi IS,
Havryltsiv ST,
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Avetikov DS,
Sorokivskyi IS,
Havryltsiv ST,
Sorokivska NМ. Optimization of local anesthesia of dental patients during cystectomies of radicular cysts that have grown into the maxillary sinus or nasal cavity. Wiad Lek. 2021;74(4):906–910.
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Aoun G,
Zaarour I,
Sokhn S,
Nasseh I. Maxillary nerve block via the greater palatine canal: An old technique revisited. J Int Soc Prev Community Dent. 2015;5(5):359–364. doi:10.4103/2231-0762.165930
[29]
Mahoney PM. Maxillary nerve block. Anesth Prog. 1977;24(2):47–49.
[30]
von Arx T,
Lozanoff S. Anterior superior alveolar nerve (ASAN). Swiss Dent J. 2015;125(11):1202–1209.
[31]
Kudo K,
Tanaka K,
Ambe K,
Kawaai H,
Yamazaki S. Immunohistochemical analysis of nerve distribution in mandible of rats. Anesth Prog. 2019;66(2):87–93. doi:10.2344/anpr-66-01-10
[32]
Ohu University Guideline for Animal Experiment. Accessed May 18, 2023. https://www.ohu-u.ac.jp/information/compliance/compliance-10.pdf
[33]
Bailey JF,
Liebenberg E,
Degmetich S,
Lotz JC. Innervation patterns of PGP 9.5-positive nerve fibers within the human lumbar vertebra. J Anat. 2011;218(3):263–270. doi:10.1111/j.1469-7580.2010.01332.x
[34]
Eftekhari S,
Warfvinge K,
Blixt FW,
Edvinsson L. Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. J. Pain. 2013;14(11):1289–1303. doi:10.1016/j.jpain.2013.03.010
[35]
Erlanger J,
Gasser HS. Electrical Signs of Nervous Activity. 2nd ed. University of Pennsylvania Press; 1968.
[36]
Kandalam U,
Kawai T,
Ravindran G, et al. Predifferentiated gingival stem cell-induced bone regeneration in rat alveolar bone defect model. Tissue Eng Part A. 2021;27(5–6):424–436. doi:10.1089/ten.TEA.2020
[37]
Jung H,
Horiuchi M,
Soma K. Changes in the distribution of nerve fibers immunoreactive to calcitonin gene-related peptide according to growth and aging in rat molar periodontal ligament. Angle Orthod. 2010;80(2): 309–315. doi:10.2319/040109-185.1
[38]
Tahmasebi-Sarvestani A,
Tedman R,
Goss AN. Distribution and coexistence of neuropeptides in nerve fibres in the temporomandibular joint of late gestation fetal sheep. J Anat. 1997;191(Pt2):245–257. doi:10.1046/j.1469-7580.1997.19120245.x
[39]
Iizuka N,
Suzuki A,
Nozawa-Inoue K, et al. Differential cell-specific location of Cav-1 and Ca(2+)-ATPase in terminal Schwann cells and mechanoreceptive Ruffini endings in the periodontal ligament of the rat incisor. J Anat. 2009;214:267–274. doi:10.1111/j.1469-7580.2008.01029.x
[40]
Matsuda H,
Sato I,
Asaumi R, et al. Comparison of CGRP distributions in the maxillary sinus and trigeminal ganglion between elderly dentulous and edentulous humans. Eur J Histochem. 2021;65(2):3234. doi:10.4081/ejh2021.3234
[41]
Park SK,
Choi SK,
Kim YG, et al. Parvalbumin-, substance P- and calcitonin gene-related peptide-immunopositive axons in the human dental pulp differ in their distribution of varicosities. Sci Rep. 2020;10(1):10672. doi:10.1038/s41598-020-67804-x
[42]
Moretto EP,
Silva GH,
Toledo Filho JL,
Andreo JC,
Navarro Rde L,
Navarro JA. Surgical anatomy of the maxillary nerve in the zygomatic region. J Appl Oral Sci. 2005;13(2):167–170. doi:10.1590/s1678-77572005000200014
[43]
Hoshino N,
Harada F,
Alkhamrah BA, et al. Involvement of brain-derived neurotrophic factor (BDNF) in the development of periodontal Ruffini endings. Anat Rec Discov Mol Cell Evol Biol. 2003;274(1):807–816. doi:10.1002/ar.a.10094
[44]
Sun Y,
Tao R,
Zhang M, et al. Expression of calcitonin gene-related peptide in rat pulp and periodontal tissues by indirect immunofluorescence method. Monoclon Antib Immunodiagn Immunother. 2013;32(6):404–408. doi:10.1089/mab.2013.0044
[45]
Okutsu Y,
Yamada A,
Tonomura S. Electrophysiological properties of maxillary trigeminal Aβ-afferent neurons of rats. Mol Pain. 2021;17:17448069211021271. doi:10.1177/17448069211021271
[46]
Edvinsson JCA,
Warfvinge K,
Krause DN, et al. C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system. J Headache Pain. 2019;20(1):105. doi:10.1186/s10194-019-1055-3
[47]
Eftekhari S,
Edvinsson L. Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level. BMC Neurosci. 2011;12:112. doi:10.1186/1471-2202-12-112
[48]
Jadhav GR,
Mittal P. Anaesthesia techniques for maxillary molars -a questionnaire- based retrospective field survey of dentist in Western India. J Clin Diagn Res. 2016;10(3):ZC15–7. doi:10.7860/JCDR/2016/16533.7352
[49]
Meechan JG. Infiltration anesthesia in the mandible. Dental Clin North Am. 2010;54(4):621–629. doi:10.1016/j.cden.2010.06.003
[50]
Abu Sharkh M,
Khalil A,
Ong-Ly C,
Wilson TD,
Galil K. Buccal injection of articaine to anesthetize the palatal mucosa. Gen Dent. 2019;67(3):26–30.
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Details
- Published
- Sep 01, 2025
- Vol/Issue
- 72(3)
- Pages
- 151-158
Authors
Cite This Article
Hikaru Moriyama, Yuki Nakase, Kimiharu Ambe, et al. (2025). Immunohistochemical Analysis of Maxillary Nerve Distribution in Rats. Anesthesia Progress, 72(3), 151-158. https://doi.org/10.2344/23-0035
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