Skip to main content

Advertisement

SpringerLink
Log in

Fos protein-like immunoreactive neurons induced by electrical stimulation in the trigeminal sensory nuclear complex of rats with chronically injured peripheral nerve

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The rat trigeminal sensory nuclear complex (TSNC) was examined for Fos protein-like immunoreactive (Fos-LI) neurons induced by electrical stimulation (ES) of the lingual nerve (LN) at 2 weeks after injury to the LN or the inferior alveolar nerve (IAN). Intensity-dependent increase in the number of Fos-LI neurons was observed in the subnucleus oralis (Vo) and caudalis (Vc) of the spinal trigeminal tract nucleus irrespective of nerve injury. The number of Fos-LI neurons induced by ES of the chronically injured LN at A-fiber intensity (0.1 mA) was significantly increased in the Vo but not the Vc. On the other hand, in rats with chronically injured IAN, the number of Fos-LI neurons induced by ES of the LN at C-fiber intensity (10 mA) was significantly increased in the Vc but not the Vo. These results indicated that injury of a nerve innervating intraoral structures increased the c-Fos response of Vo neurons to A-fiber intensity ES of the injured nerve. A similar nerve injury enhanced the c-Fos response of Vc neurons to C-fiber intensity ES of a spared uninjured nerve innervating an intraoral territory neighboring that of the injured nerve. The present result show that nerve injury causes differential effects on c-Fos expression in the Vo and Vc, which may explain complexity of neuropathic pain symptoms in clinical cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Bullitt E (1990) Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol 296:517–530

    Article  PubMed  CAS  Google Scholar 

  • Dai Y, Kondo E, Fukuoka T, Tokunaga A, Miki K, Noguchi K (2001) The effect of electroacupuncture on pain behaviors and noxious stimulus-evoked Fos expression in a rat model of neuropathic pain. J Pain 2:151–159

    Article  PubMed  CAS  Google Scholar 

  • Dallel R, Ricard O, Raboisson P (2004) Organization of parabrachial projections from the spinal trigeminal nucleus oralis: an anterograde tracing study in the rat. J Comp Neurol 470:181–191. doi:10.1002/cne.11043

    Article  PubMed  Google Scholar 

  • Devor M, Govrin-Lippmann R (1983) Axoplasmic transport block reduces ectopic impulse generation in injured peripheral nerves. Pain 16:73–85

    Article  PubMed  CAS  Google Scholar 

  • Devor M, Wall PD (1978) Reorganisation of spinal cord sensory map after peripheral nerve injury. Nature 276:75–76

    Article  PubMed  CAS  Google Scholar 

  • Dubner R, Bennett GJ (1983) Spinal and trigeminal mechanisms of nociception. Annu Rev Neurosci 6:381–418. doi:10.1146/annurev.ne.06.030183.002121

    Article  PubMed  CAS  Google Scholar 

  • Govrin-Lippmann R, Devor M (1978) Ongoing activity in severed nerves: source and variation with time. Brain Res 159:406–410

    Article  PubMed  CAS  Google Scholar 

  • Hughes AS, Averill S, King VR, Molander C, Shortland PJ (2008) Neurochemical characterization of neuronal populations expressing protein kinase C gamma isoform in the spinal cord and gracile nucleus of the rat. Neuroscience 153:507–517. doi:10.1016/j.neuroscience.2008.01.082

    Article  PubMed  CAS  Google Scholar 

  • Hunt SP, Pini A, Evan G (1987) Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 328:632–634

    Article  PubMed  CAS  Google Scholar 

  • Hylden JL, Nahin RL, Dubner R (1987) Altered responses of nociceptive cat lamina I spinal dorsal horn neurons after chronic sciatic neuroma formation. Brain Res 411:341–350

    Article  PubMed  CAS  Google Scholar 

  • Korenman EM, Devor M (1981) Ectopic adrenergic sensitivity in damaged peripheral nerve axons in the rat. Exp Neurol 72:63–81

    Article  PubMed  CAS  Google Scholar 

  • Lisney SJ (1983) Changes in the somatotopic organization of the cat lumbar spinal cord following peripheral nerve transection and regeneration. Brain Res 259:31–39

    Article  PubMed  CAS  Google Scholar 

  • Luccarini P, Cadet R, Saade M, Woda A (1995) Antinociceptive effect of morphine microinjections into the spinal trigeminal subnucleus oralis. NeuroReport 6:365–368

    Article  PubMed  CAS  Google Scholar 

  • Markus H, Pomeranz B, Krushelnycky D (1984) Spread of saphenous somatotopic projection map in spinal cord and hypersensitivity of the foot after chronic sciatic denervation in adult rat. Brain Res 296:27–39

    Article  PubMed  CAS  Google Scholar 

  • Miki K, Fukuoka T, Tokunaga A, Noguchi K (1998) Calcitonin gene-related peptide increase in the rat spinal dorsal horn and dorsal column nucleus following peripheral nerve injury: up-regulation in a subpopulation of primary afferent sensory neurons. Neuroscience 82:1243–1252

    Article  PubMed  CAS  Google Scholar 

  • Molander C, Hongpaisan J, Grant G (1992) Changing pattern of c-FOS expression in spinal cord neurons after electrical stimulation of the chronically injured sciatic nerve in the rat. Neuroscience 50:223–236

    Article  PubMed  CAS  Google Scholar 

  • Molander C, Hongpaisan J, Shortland P (1998) Somatotopic redistribution of c-fos expressing neurons in the superficial dorsal horn after peripheral nerve injury. Neuroscience 84:241–253

    Article  PubMed  CAS  Google Scholar 

  • Noguchi K, Kawai Y, Fukuoka T, Senba E, Miki K (1995) Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons. J Neurosci 15:7633–7643

    PubMed  CAS  Google Scholar 

  • Nomura H, Ogawa A, Tashiro A, Morimoto T, Hu JW, Iwata K (2002) Induction of Fos protein-like immunoreactivity in the trigeminal spinal nucleus caudalis and upper cervical cord following noxious and non-noxious mechanical stimulation of the whisker pad of the rat with an inferior alveolar nerve transection. Pain 95:225–238

    Article  PubMed  CAS  Google Scholar 

  • Okada-Ogawa A, Suzuki I, Sessle BJ et al (2009) Astroglia in medullary dorsal horn (trigeminal spinal subnucleus caudalis) are involved in trigeminal neuropathic pain mechanisms. J Neurosci 29:11161–11171. doi:10.1523/jneurosci.3365-09.2009

    Article  PubMed  CAS  Google Scholar 

  • Raboisson P, Bourdiol P, Dallel R, Clavelou P, Woda A (1991) Responses of trigeminal subnucleus oralis nociceptive neurones to subcutaneous formalin in the rat. Neurosci Lett 125:179–182

    Article  PubMed  CAS  Google Scholar 

  • Scadding JW (1981) Development of ongoing activity, mechanosensitivity, and adrenaline sensitivity in severed peripheral nerve axons. Exp Neurol 73:345–364

    Article  PubMed  CAS  Google Scholar 

  • Sessle BJ (2000) Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 11:57–91

    Article  PubMed  CAS  Google Scholar 

  • Shortland P, Molander C (1998) The time-course of abeta-evoked c-fos expression in neurons of the dorsal horn and gracile nucleus after peripheral nerve injury. Brain Res 810:288–293

    Article  PubMed  CAS  Google Scholar 

  • Strassman AM, Vos BP (1993) Somatotopic and laminar organization of fos-like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat. J Comp Neurol 331:495–516

    Article  PubMed  CAS  Google Scholar 

  • Strassman AM, Vos BP, Mineta Y, Naderi S, Borsook D, Burstein R (1993) Fos-like immunoreactivity in the superficial medullary dorsal horn induced by noxious and innocuous thermal stimulation of facial skin in the rat. J Neurophysiol 70:1811–1821

    PubMed  CAS  Google Scholar 

  • Sugimoto T, Ichikawa H, Hijiya H, Mitani S, Nakago T (1993) c-Fos expression by dorsal horn neurons chronically deafferented by peripheral nerve section in response to spared, somatotopically inappropriate nociceptive primary input. Brain Res 621:161–166

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Hara T, Shirai H, Abe T, Ichikawa H, Sato T (1994a) c-fos induction in the subnucleus caudalis following noxious mechanical stimulation of the oral mucous membrane. Exp Neurol 129:251–256

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Ichikawa H, Mitani S, Hitsu A, Nakago T, Nakago T (1994b) Changes in c-fos induction in dorsal horn neurons by hindpaw formalin stimulation following tibial neurotomy. Brain Res 642:348–354

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Yoshida A, Nishijima K, Ichikawa H (1994c) c-Fos induction in the rat spinal dorsal horn partially deafferented by dorsal rhizotomy. Neurosci Lett 178:239–242

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Fujiyoshi Y, Xiao C, He YF, Ichikawa H (1997) Central projection of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive trigeminal primary neurons in the rat. J Comp Neurol 378:425–442. doi:10.1002/(SICI)1096-9861(19970217)378:3<425:AID-CNE9>3.0.CO;2-5

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, He YF, Funahashi M, Ichikawa H (1998a) Induction of immediate-early genes c-fos and zif268 in the subnucleus oralis by noxious tooth pulp stimulation. Brain Res 794:353–358

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, He YF, Xiao C, Ichikawa H (1998b) c-fos induction in the subnucleus oralis following trigeminal nerve stimulation. Brain Res 783:158–162

    Article  PubMed  CAS  Google Scholar 

  • Takemura M, Sugimoto T, Sakai A (1987) Topographic organization of central terminal region of different sensory branches of the rat mandibular nerve. Exp Neurol 96:540–557

    Article  PubMed  CAS  Google Scholar 

  • Takemura M, Sugimoto T, Shigenaga Y (1991) Difference in central projection of primary afferents innervating facial and intraoral structures in the rat. Exp Neurol 111:324–331

    Article  PubMed  CAS  Google Scholar 

  • Takemura M, Shimada T, Sugiyo S, Nokubi T, Shigenaga Y (2000) Mapping of c-Fos in the trigeminal sensory nucleus following high- and low-intensity afferent stimulation in the rat. Exp Brain Res 130:113–123

    Article  PubMed  CAS  Google Scholar 

  • Terayama R, Omura S, Fujisawa N, Yamaai T, Ichikawa H, Sugimoto T (2008) Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury. Neuroscience 153:1245–1255. doi:10.1016/j.neuroscience.2008.03.041

    Article  PubMed  CAS  Google Scholar 

  • Tokunaga A, Kondo E, Fukuoka T, Miki K, Dai Y, Tsujino H, Noguchi K (1999) Excitability of spinal cord and gracile nucleus neurons in rats with chronically chronically injured sciatic nerve examined by c-fos expression. Brain Res 847:321–331

    Article  PubMed  CAS  Google Scholar 

  • Wall PD, Waxman S, Basbaum AI (1974) Ongoing activity in peripheral nerve: injury discharge. Exp Neurol 45:576–589

    Article  PubMed  CAS  Google Scholar 

  • Woda A (2003) Pain in the trigeminal system: from orofacial nociception to neural network modeling. J Dent Res 82:764–768

    Article  PubMed  CAS  Google Scholar 

  • Yonehara N, Kudo C, Kamisaki Y (2003) Involvement of NMDA-nitric oxide pathways in the development of tactile hypersensitivity evoked by the loose-ligation of inferior alveolar nerves in rats. Brain Res 963:232–243

    Article  PubMed  CAS  Google Scholar 

  • Yoshida A, Ichikawa H, Sugimoto T (1995) CGRP in peripherally axotomized mesencephalic trigeminal neurones of the rat. NeuroReport 6:837–840

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann M (2001) Pathobiology of neuropathic pain. Eur J Pharmacol 429:23–37

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (20592324, 22592035).

Author information

Authors and Affiliations

  1. Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Naoko Fujisawa, Ryuji Terayama, Daisuke Yamaguchi, Shinji Omura & Tomosada Sugimoto

  2. Department of Orthodontics and Dentofacial Orthopedics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan

    Naoko Fujisawa & Takashi Yamashiro

  3. ASAHI College of Medical Art and Sciences, Okayama, 700-0013, Japan

    Daisuke Yamaguchi & Shinji Omura

Authors
  1. Naoko Fujisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryuji Terayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shinji Omura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Yamashiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomosada Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryuji Terayama.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fujisawa, N., Terayama, R., Yamaguchi, D. et al. Fos protein-like immunoreactive neurons induced by electrical stimulation in the trigeminal sensory nuclear complex of rats with chronically injured peripheral nerve. Exp Brain Res 219, 191–201 (2012). https://doi.org/10.1007/s00221-012-3078-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-012-3078-8

Keywords

Search

Navigation