5-HTr Expression in Primary Trigeminal Neuron Following Injury

Download Download as PDF (Size:288KB)  HTML    PP. 427-435  
DOI: 10.4236/jbbs.2012.24050    2,133 Downloads   4,301 Views  


Trigeminal ganglia neurons significantly affect the amplitude and type of 5-HT receptor gene expression following activation of their axon terminals and sensitisation by painful stimuli. Moreover, these neurons significantly alter gene expression in cytoskeletal proteins following injury. The aim of the present study was to determine whether peripheral and/or central deafferenting lesions affect gene expression in serotonergic receptors that are involved in pain transmission. Adult rats were subjected to unilateral ablation of the facial sensory and motor cortices. Fifteen days after the surgery, degeneration of the cortico-trigeminal pathway was observed. Presynaptic deafferentation of the primary trigeminal neurons and central afferents of the contralateral ganglia was conducted. As a consequence of the excision of the meninges covering the ablated cortices, the peripheral axotomy of the trigeminal-vascular primary neurons of the ipsi-lateral side was induced. Serotonergic receptor (5-HT5A/5B/1B/1D/1F) gene expression was analysed in both sides of the trigeminal ganglia neurons. The results of the present study showed a significant increase in 5-HT5A/5B/1B/1D receptor gene expression in the primary sensory neurons of both ganglia, with the highest levels of expression noted in the ganglia contralateral to the lesion. 5-HT1F receptor expression, however, was more strongly expressed in the ganglia ipsilateral to the lesion. Our results also confirm that the adaptive response of primary trigeminal neurons to injury involves anatomical remodelling, as well as changes in receptor gene expression involved in sensory transmission. This may explain the distortion of sensory signals observed in trigeminal neuropathic states, and may lead to the development of novel pharmacological interventions.

Cite this paper

O. Mameli, A. Russo, S. Stanzani, G. Tringali, E. Insirello, M. Caria and P. Riu, "5-HTr Expression in Primary Trigeminal Neuron Following Injury," Journal of Behavioral and Brain Science, Vol. 2 No. 4, 2012, pp. 427-435. doi: 10.4236/jbbs.2012.24050.


[1] P. L. De Riu, A. Russo, R. Pellitteri, S. Stanzani, G. Tringali, A. M. Roccazzello, G. De Riu, P. Marongiu and O. Mameli, “Primary Afferent Plasticity Following Deafferentation of the Trigeminal Brainstem Nuclei in the Adult Rat,” Experimental Neurology, Vol. 213, No. 1, 2008, pp. 101-107. doi:10.1016/j.expneurol.2008.05.010
[2] J. O. Dostrovsky, K. D. Davis and K. Kawakita, “Central Mechanisms of Vascular Headaches,” Canadian Journal of Physiology and Pharmacology, Vol. 69, No. 5, 1991, pp. 652-658. doi:10.1139/y91-097
[3] G. M. Bove and M. A. Moskowitz, “Primary Afferent Neurons Innervating Guinea Pig Dura,” Journal of Neurophysiology, Vol. 77, No. 1, 1997, 299-308.
[4] D. Levy, M. Jakubowski and R. Burstein, “Disruption of Communication between Peripheral and Central Trigeminovascular Neurons Mediates the Antimigraine Action of 5HT1B/1D Receptor Agonists,” Proceedings of the National Academy of Sciences, Vol. 101, No. 12, 2004, pp. 4274-4279. doi:10.1073/pnas.0306147101
[5] A. M. Strassman and D. Levy, “Response Properties of Dural Nociceptors in Relation to Headache,” Journal of Neurophysiology, Vol. 95, No. 3, 2006, pp. 1298-1306. doi:10.1152/jn.01293.2005
[6] A. M. Strassman, S. A. Raymond and R. Burstein, “Sensitization of Meningeal Sensory Neurons and the Origin of Headaches,” Nature, Vol. 384, No. 6609, 1996, pp. 560-564. doi:10.1038/384560a0
[7] D. Levy and A. M. Strassman, “Mechanical Response Properties of A and C Primary Afferent Neurons Innervating the Rat Intracranial Dura,” Journal of Neurophysiology, Vol. 88, No. 6, 2002, pp. 3021-3031. doi:10.1152/jn.00029.2002
[8] D. Levy and A. M. Strassman, “Distinct Sensitizing Effects of the cAMP/PKA Second Messenger Cascade on Rat Dural Mechanonociceptors,” Journal of Physiology, Vol. 538, No. 2, 2002, pp. 483-493. doi:10.1113/jphysiol.2001.013175
[9] G. Bonvento, E. T. MacKenzie and L. Edvinsson, “Serotoninergic Innervation of the Cerebral Vasculature: Relevance to Migraine and Ischaemia,” Brain Research Reviews, Vol. 16, No. 3, 1991, pp. 257-263. doi:10.1016/0165-0173(91)90009-W
[10] P. M. Waite and D. J. Tracy, “Trigeminal Sensory System,” In: G. Paxynos, Ed., The Rat Nervous System, Academic Press, San Diego, 1995, pp. 714-724.
[11] I. Darian-Smith and T. Yokota, “Cortically Evoked Depolarisation of Trigeminal Cutaneous Afferent Fibres in the Cat,” Journal of Neurophysiology, Vol. 29, No. 2, 1966, pp. 170-184.
[12] I. Darian-Smith and T. Yokota, “Corticofugal Effects on Different Neuron Types within the Cat’s Brain-Stem Activated by Tactile Stimulation of the Face,” Journal of Neurophysiology, Vol. 29, No. 2, 1966, pp. 185-206.
[13] E. Welker, P. V. Hoogland and H. Van Der Loos, “Organization of Feedback and Feedforword Projections of the Barrel Cortex: A PHA-L Study in the Mouse,” Experimental Brain Research, Vol. 73, No. 2, 1988, pp. 411- 435. doi:10.1007/BF00248234
[14] J. W. Geddes, K. J. Anderson and C. W. Cotman, “Senile Plaque as Aberrant Stimulating Structure,” Experimental Neurology, Vol. 94, No. 3, 1986, pp. 767-776. doi:10.1016/0014-4886(86)90254-2
[15] M. A. Moscowitz, “Neurogenic Inflammation in the Patophysiology and Treatment of Migrane,” Neurology, Vol. 43, No. 6, 1993, pp. S16-S20.
[16] K. W. Johnson, J. M. Schaus, M. M. Durkin, J. E. Audia, S. W. Kaldor, M. E. Flaugh, N. Adham, J. M. Zgombick, M. L. Cohen, T. A. Branchek and L. A. Phebus, “5-HT1F Receptor Agonists Inhibit Neurogenic Dural Inflammation in Guinea Pigs,” Neuroreport, Vol. 8, No. 9, 1997, pp. 2237-2240. doi:10.1097/00001756-199707070-00029
[17] N. M. Barnes and T. Sharp, “A Review of Central 5-HT Receptors and Their Function,” Neuropharmacology, Vol. 38, No. 8, 1999, pp. 1083-1152. doi:10.1016/S0028-3908(99)00010-6
[18] R. J. Storer and P. J. Goadsby, “Trigeminovascular Nociceptive Transmission Involves N-Methyl-D-aspartate and Non-N-methyl-D-aspartate Glutamate Receptors,” Neuroscience, Vol. 90, No. 4, 1999, pp. 1371-1376.
[19] C. J. Woolf and Z. Wiesenfeld-Hallin, “Substance P and Calcitonin Gene-Related Peptide Synergistically Modulate the Gain of Nociceptive Flexor Withdrawal Reflex in the Rat,” Neuroscience Letters, Vol. 66, No. 2, 1986, pp. 319- 323. doi:10.1016/0304-3940(86)90195-3
[20] H. L. Fields, M. M. Heinricher and P. Mason, “Neurotrasmitters in Nociceptive Modulatory Circuits,” Annual Review of Neuroscience, Vol. 14, 1991, pp. 219-245. doi:10.1146/annurev.ne.14.030191.001251
[21] S. Doly, J. Fischer, M.-J. Brisorgueil, D. Vergé and M. Conrath, “5-HT5A Receptor Localization in the Rat Spinal Cord Suggests a Role in Nociception and Control of Pelvic Floor Musculature,” Journal of Comparative Neurology, Vol. 476, No. 4, 2004, pp. 316-329. doi:10.1002/cne.20214
[22] S. Hochman, S. M. Garraway, D. W. Machacek and B. L. Shay, “5-HT Receptors and the Neuromodulator Control of Spinal Cord Function,” In: T. C. Cope, Ed., Motor Neurobiology of the Spinal Cord, CRC Press, Boca Raton, 2001, pp. 1-40.
[23] D. L. Nelson, “5-HT5 Receptors,” Current Drug Target- CNS & Neurological Disorders, Vol. 3, No. 1, 2004, pp. 53-58. doi:10.2174/1568007043482606
[24] B. Volk, B. J. Nagy, S. Vas, D. Kostyalik, G. Simig and G. Bagdy, “Medicinal Chemistry of 5-HT5A Receptor Ligands: A Receptor Subtype with Unique Therapeutical Potential,” Current Topics in Medicinal Chemistry, Vol. 10, No. 5 2010, pp. 554-578. doi:10.2174/156802610791111588
[25] S. P. Wise, E. A. Murray and J. D. Coulter, “Somatotopic Organization of Corticospinal and Corticotrigeminal Neurons in the Rat,” Neuroscience, Vol. 4, No. 1, 1979, pp. 65-78. doi:10.1016/0306-4522(79)90218-5
[26] R. C. Dunn and D. J. Tolber, “The Corticotrigeminal Projection in the Cat. A Study on the Organization of Cortical Projections to the Spinal Trigeminal Nucleus,” Brain Research, Vol. 240, No. 1, 1982, pp. 13-25. doi:10.1016/0006-8993(82)90640-0
[27] R. Dubner and B. J. Sessle, “Presynaptic Excitability Changes of Primary Afferents and Corticofugal Fibres Projecting to Trigeminal Brain-Stem Nuclei,” Experimental Neurology, Vol. 30, No. 2, 1971, pp. 223-238. doi:10.1016/S0014-4886(71)80003-1
[28] N. L. Chiaia, C. A. Bennet-Clarke and R. W. Rhoades, “Effects of Cortical and Thalamic Lesions upon Primary Afferent Terminations, Distributions of Projecting Neurons and Cytochrome Oxidase Pattern in the Trigeminal Brain Stem-Complex,” Journal of Comparative Neurology, Vol. 303, No. 4, 1991, pp. 600-616. doi:10.1002/cne.903030407

comments powered by Disqus

Copyright © 2017 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.