Skip to main content
SpringerLink
Log in

No overlap of sensitivity to capsaicin and expression of galanin in rat dorsal root ganglion neurons after axotomy

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

Abstract

The neuropeptide galanin is known to have an antinociceptive effect under neuropathic conditions. After axotomy, galanin is upregulated in sensory neurons, presumably in the capsaicin-sensitive ones. Here, the sensitivity to capsaicin and the expression of galanin were simultaneously examined by double-staining in individual, dissociated rat dorsal root ganglion neurons (1) after axotomy of the sciatic nerve for up to 14 days and (2) in culture for up to 4 days without prior nerve injury. Ten days after axotomy, the proportion of capsaicin-sensitive neurons had decreased by 36 percentage points (from 63% to 27%), whereas the proportion of galaninergic neurons had increased by 33 percentage points (from 3% to 36%). These changes were also observed in neurons kept in culture, where the regulation was attenuated by the addition of nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) to the medium. After axotomy, galaninergic neurons had a soma size-distribution profile similar to the capsaicin-sensitive neurons, but there was no colocalization of capsaicin sensitivity and galanin expression in individual neurons. In culture, some neurons showed colocalization after 30 h and 48 h, but not after 6 h or 96 h. We conclude that the upregulation of galanin in an individual neuron is preceded by downregulation of its capsaicin sensitivity both in NGF-dependent peptidergic and in GDNF-dependent non-peptidergic neurons, indicating a change in phenotype.

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. a
Fig. 2. a
Fig. 3.

Similar content being viewed by others

References

  • Amaya F, Oh-hashi K, Naruse Y et al. (2003) Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res 963:190–196

    Article  PubMed  Google Scholar 

  • Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV (1995) Immunocytochemical localization of trkα receptors in chemically identified subgroups of adult-rat sensory neurons. Eur J Neurosci 7:1484–1494

    CAS  PubMed  Google Scholar 

  • Bennett DL, Michael GJ, Ramachandran N et al. (1998) A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury. J Neurosci 18:3059–3072

    CAS  PubMed  Google Scholar 

  • Bevan S, Winter J (1995) Nerve growth factor (NGF) differentially regulates the chemosensitivity of adult rat cultured sensory neurons. J Neurosci 15:4918–4926

    CAS  PubMed  Google Scholar 

  • Blakeman KH, Holmberg K, Hao JX et al. (2001) Mice over-expressing galanin have elevated heat nociceptive threshold. Neuroreport 12:423–425

    CAS  PubMed  Google Scholar 

  • Blakeman KH, Hao JX, Xu XJ et al. (2003) Hyperalgesia and increased neuropathic pain-like response in mice lacking galanin receptor 1 receptors. Neuroscience 117:221–227

    Article  CAS  PubMed  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    CAS  PubMed  Google Scholar 

  • Caterina MJ, Leffler A, Malmberg AB et al. (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313

    Article  CAS  PubMed  Google Scholar 

  • Ch'ng JL, Christofides ND, Anand P et al. (1985) Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury. Neuroscience 16:343–354

    Article  CAS  PubMed  Google Scholar 

  • Corness J, Shi TJ, Xu ZQ, Brulet P, Hökfelt T (1996) Influence of leukemia inhibitory factor on galanin/GMAP and neuropeptide Y expression in mouse primary sensory neurons after axotomy. Exp Brain Res 112:79–88

    CAS  PubMed  Google Scholar 

  • Corness J, Stevens B, Fields RD, Hökfelt T (1998) NGF and LIF both regulate galanin gene expression in primary DRG cultures. Neuroreport 9:1533–1536

    CAS  PubMed  Google Scholar 

  • Davis JB, Gray J, Gunthorpe MJ et al. (2000) Vanilloid receptor-1 is essential for inflammatory hyperalgesia. Nature 405:183–187

    Article  CAS  PubMed  Google Scholar 

  • Gardiner NJ, Cafferty WBJ, Slack SE, Thompson SWN (2002) Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. J Neurochem 83:100–109

    Article  CAS  PubMed  Google Scholar 

  • Hökfelt T, Wiesenfeld-Hallin Z, Villar M, Melander T (1987) Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci Lett 83:217–220

    PubMed  Google Scholar 

  • Hökfelt T, Zhang X, Wiesenfeld-Hallin Z (1994) Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci 17:22–30

    Article  PubMed  Google Scholar 

  • Hogan PG (1983) Expression of markers for pain sensory neurons in cell culture. PhD Thesis, Harvard University, Cambridge, MA, USA

  • Hu-Tsai M, Woolf C, Winter J (1996) Influence of inflammation or disconnection from peripheral target tissue on the capsaicin sensitivity of rat dorsal root ganglion sensory neurones. Neurosci Lett 203:119–122

    Article  CAS  PubMed  Google Scholar 

  • Jancsó G, Kiraly E, Jancsó-Gábor A (1977) Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature 270:741–743

    PubMed  Google Scholar 

  • Ji RR, Zhang X, Zhang Q et al. (1995) Central and peripheral expression of galanin in response to inflammation. Neuroscience 68:563–576

    CAS  PubMed  Google Scholar 

  • Johnson EM, Taniuchi M, Clark HB et al. (1987) Demonstration of the retrograde transport of nerve growth factor receptor in the peripheral and central nervous system. J Neurosci 7:923–929

    CAS  PubMed  Google Scholar 

  • Kerekes N, Landry M, Rydh-Rinder M, Hökfelt T (1997) The effect of NGF, BDNF and βFGF on expression of galanin in cultured rat dorsal root ganglia. Brain Res 754:131–141

    Article  CAS  PubMed  Google Scholar 

  • Kerekes N, Landry M, Hökfelt T (1999) Leukemia inhibitory factor regulates galanin/galanin message-associated peptide expression in cultured mouse dorsal root ganglia; with a note on in situ hybridization methodology. Neuroscience 89:1123–1134

    Article  CAS  PubMed  Google Scholar 

  • Kerr BJ, Cafferty WB, Gupta YK et al. (2000) Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury. Eur J Neurosci 12:793–802

    Article  CAS  PubMed  Google Scholar 

  • Kerr BJ, Gupta Y, Pope R, Thompson SWN, Wynick D, McMahon SB (2001) Endogenous galanin potentiates spinal nociceptive processing following inflammation. Pain 93:267–277

    Article  CAS  PubMed  Google Scholar 

  • Kidd BL, Urban LA (2001) Mechanisms of inflammatory pain. Br J Anaesth 87:3-11

    Article  CAS  PubMed  Google Scholar 

  • Leitner ML, Molliver DC, Osborne PA et al. (1999) Analysis of the retrograde transport of glial cell line-derived neurotrophic factor (GDNF), neurturin, and persephin suggests that in vivo signaling for the GDNF family is GFRalpha coreceptor-specific. J Neurosci 19:9322–9331

    CAS  PubMed  Google Scholar 

  • Liu HX, Hökfelt T (2002) The participation of galanin in pain processing at the spinal level. Trends Pharmacol Sci 23:468–474

    Article  CAS  PubMed  Google Scholar 

  • Michael GJ, Priestley JV (1999) Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. J Neurosci 19:1844–1854

    CAS  PubMed  Google Scholar 

  • Noguchi K, De Leon M, Nahin RL, Senba E, Ruda MA (1993) Quantification of axotomy-induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment. J Neurosci Res 35:54–66

    CAS  PubMed  Google Scholar 

  • Ogun-Muyiwa P, Helliwell R, McIntyre P, Winter J (1999) Glial cell line derived neurotrophic factor (GDNF) regulates VR1 and substance P in cultured sensory neurons. Neuroreport 10:2107–2111

    CAS  PubMed  Google Scholar 

  • Petersen M, Segond von Banchet G, Heppelmann B, Koltzenburg M (1998) Nerve growth factor regulates the expression of bradykinin binding sites on adult sensory neurons via the neurotrophin receptor p75. Neuroscience 83:161–168

    Article  CAS  PubMed  Google Scholar 

  • Scadding JW (1980) The permanent anatomical effects of neonatal capsaicin on somatosensory nerves. J Anat 131:471–482

    PubMed  Google Scholar 

  • Shadiack A, Sun Y, Zigmond R (2001) Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons. J Neurosci 21:363–371

    CAS  PubMed  Google Scholar 

  • Skofitsch G, Jacobowitz DM (1985) Galanin-like immunoreactivity in capsaicin sensitive sensory neurons and ganglia. Brain Res Bull 15:191–195

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Zigmond RE (1996) Leukaemia inhibitory factor induced in the sciatic nerve after axotomy is involved in the induction of galanin in sensory neurons. Eur J Neurosci 8:2213–2220

    CAS  PubMed  Google Scholar 

  • Thompson SW, Vernallis AB, Heath JK, Priestley JV (1997) Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers. Eur J Neurosci 9:1244–1251

    CAS  PubMed  Google Scholar 

  • Verge VMK, Richardson PM, Wiesenfeld-Hallin Z, Hökfelt T (1995) Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons. J Neurosci 15:2081–2096

    CAS  PubMed  Google Scholar 

  • Villar MJ, Cortes R, Theodorsson E et al. (1989) Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin. Neuroscience 33:587–604

    CAS  PubMed  Google Scholar 

  • Wendland JR, Schmidt K, Schneider M, Koltzenburg M, Petersen M (1999) Normal or axotomized galanin-containing DRG neurons are not capsaicin-sensitive in the rat. Soc Neurosci Abstr 25:690

    Google Scholar 

  • Wiesenfeld-Hallin Z, Xu XJ, Villar MJ, Hökfelt T (1989) The effect of intrathecal galanin on the flexor reflex in rat: increased depression after sciatic nerve section. Neurosci Lett 105:149–154

    Article  CAS  PubMed  Google Scholar 

  • Wiesenfeld-Hallin Z, Xu XJ, Langel U, Bedecs K, Hökfelt T, Bartfai T (1992) Galanin-mediated control of pain: enhanced role after nerve injury. Proc Natl Acad Sci USA 89:3334–3337

    CAS  PubMed  Google Scholar 

  • Winter J (1987) Characterization of capsaicin-sensitive neurones in adult rat dorsal root ganglion cultures. Neurosci Lett 80:134–140

    Article  CAS  PubMed  Google Scholar 

  • Winter J, Forbes CA, Sternberg J, Lindsay RM (1988) Nerve growth factor (NGF) regulates adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin. Neuron 1:973–981

    CAS  PubMed  Google Scholar 

  • Xu IS, Grass S, Xu XJ, Wiesenfeld-Hallin Z (1998) On the role of galanin in mediating spinal flexor reflex excitability in inflammation. Neurosci 85:827–835

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We wish to thank Andreas Klusch, BA, for help in the preparation of the manuscript. This work was supported by SFB 353 to M.P. and M.K.

Author information

Authors and Affiliations

  1. Department of Physiology, University of Würzburg, Roentgenring 9, 97070, Würzburg, Germany

    Jens R. Wendland & Marlen Petersen

  2. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany

    Klaus H. Schmidt

  3. Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK

    Martin Koltzenburg

Authors
  1. Jens R. Wendland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus H. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Koltzenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marlen Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marlen Petersen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wendland, J.R., Schmidt, K.H., Koltzenburg, M. et al. No overlap of sensitivity to capsaicin and expression of galanin in rat dorsal root ganglion neurons after axotomy. Exp Brain Res 153, 1–6 (2003). https://doi.org/10.1007/s00221-003-1562-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-003-1562-x

Keywords

Search

Navigation