Skip to main content
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2008 Feb 1;23(4):215–220. doi: 10.1007/s12264-007-0032-z

Regulatory effect of nerve growth factor on release of substance P in cultured dorsal root ganglion neurons of rat

神经生长因子对培养的大鼠背根神经节神经元 P 物质释放的调节作用

Xiang-Dong Yang 1, Zhen Liu 2, Hua-Xiang Liu 3, Li-Hong Wang 2, Chun-Hong Ma 4, Zhen-Zhong Li 2,
PMCID: PMC5550584  PMID: 17687396

Abstract

Objective

To investigate the regulatory effects of nerve growth factor (NGF) on basal and capsaicin-induced release of neuropeptide substance P (SP) in primary cultured embryonic rat dorsal root ganglion (DRG) neurons.

Methods

DRGs were dissected from 15-day-old embryonic Wistar rats. DRG neurons were dissociated and cultured, and then exposed to different concentrations of NGF (10 ng/mL, 30 ng/mL, or 100 ng/mL) for 72 h. The neurons cultured in media without NGF served as control. RT-PCR were used for detecting the mRNAs of SP and vanilloid receptor 1 (VR1) in the DRG neurons. The SP basal and capsaicin (100 nmol/L)-induced release in the culture were measured by radioimmunoassay (RIA).

Results

SP mRNA and VR1 mRNA expression increased in primary cultured DRG neurons in a dose-dependent manner of NGF. Both basal release and capsaicin-evoked release of SP increased in NGF-treated DRG neurons compared with in control group. The capsaicin-evoked release of SP also increased in a dose-dependent manner of NGF.

Conclusion

NGF may promote both basal release and capsaicin-evoked release of SP. NGF might increase the sensitivity of nociceptors by increasing the SP mRNA or VR1 mRNA.

Keywords: nerve growth factor, dorsal root ganglion, capsaicin, vanilloid receptor 1, substance P

References

  • [1].Price T.J., Louria M.D., Candelario-Soto D., Dussor G.O., Jeske N.A., Patwardhan A.M., et al. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion. BMC Neuroscience. 2005;6:4–18. doi: 10.1186/1471-2202-6-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Petruska J.C., Mendell L.M. The many functions of nerve growth factor: multiple actions on nociceptors. Neurosci Lett. 2004;361:168–171. doi: 10.1016/j.neulet.2003.12.012. [DOI] [PubMed] [Google Scholar]
  • [3].Merighi A., Carmignoto G., Gobbo S., Lossi L., Salio C., Vergnano A.M., et al. Neurotrophins in spinal cord nociceptive pathways. Prog Brain Res. 2004;146:291–321. doi: 10.1016/S0079-6123(03)46019-6. [DOI] [PubMed] [Google Scholar]
  • [4].Lazar J., Szabo T., Marincsak R., Kovacs L., Blumberg P.M., Biro T. Sensitization of recombinant vanilloid receptor-1 by various neurotrophic factors. Life Sci. 2004;75:153–163. doi: 10.1016/j.lfs.2003.11.023. [DOI] [PubMed] [Google Scholar]
  • [5].Kasai M., Mizumura K. Endogenous nerve growth factor increases the sensitivity to bradykinin in small dorsal root ganglion neurons of adjuvant inflamed rats. Neurosci Lett. 1999;272:41–44. doi: 10.1016/S0304-3940(99)00568-6. [DOI] [PubMed] [Google Scholar]
  • [6].Shu X., Mendell L.M. Acute sensitization by NGF of the response of small-diameter sensory neurons to capsaicin. J Neurophysiol. 2001;86:2931–2938. doi: 10.1152/jn.2001.86.6.2931. [DOI] [PubMed] [Google Scholar]
  • [7].Galoyan S.M., Petruska J.C., Mendell L.M. Mechanisms of sensitization of the response of single dorsal root ganglion cells from adult rat to noxious heat. Eur J Neurosci. 2003;18:535–541. doi: 10.1046/j.1460-9568.2003.02775.x. [DOI] [PubMed] [Google Scholar]
  • [8].Ji R.R., Samad T.A., Jin S.X., Schmoll R., Woolf C.J. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron. 2002;36:57–68. doi: 10.1016/S0896-6273(02)00908-X. [DOI] [PubMed] [Google Scholar]
  • [9].Chuang H., Prescott E.D., Kong H., Shields S., Jordt S.E., Basbaum A.I., et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature. 2001;411:957–962. doi: 10.1038/35082088. [DOI] [PubMed] [Google Scholar]
  • [10].Di Marzo V., Blumberg P.M., Szallasi A. Endovanilloid signaling in pain. Curr Opin Neurobiol. 2002;12:372–379. doi: 10.1016/S0959-4388(02)00340-9. [DOI] [PubMed] [Google Scholar]
  • [11].Rigoni M., Trevisani M., Gazzieri D., Nadaletto R., Tognetto M., Creminon C., et al. Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin. Br J Pharmacol. 2003;138:977–985. doi: 10.1038/sj.bjp.0705110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Nemeth J., Reglodi D., Pozsgai G., Szabo A., Elekes K., Pinter E., et al. Effect of pituitary adenylate cyclase activating polypeptide-38 on sensory neuropeptide release and neurogenic inflammation in rats and mice. Neuroscience. 2006;143:223–230. doi: 10.1016/j.neuroscience.2006.07.028. [DOI] [PubMed] [Google Scholar]
  • [13].Ribeiro-da-Silva A., Hökfelt T. Neuroanatomical localisation of substance P in the CNS and sensory neurons. Neuropeptides. 2000;34:256–271. doi: 10.1054/npep.2000.0834. [DOI] [PubMed] [Google Scholar]
  • [14].Kim H.S., Yumkham S., Kim S.H., Yea K., Shin Y.C., Ryu S.H., et al. Secretin induces neurite outgrowth of PC12 through cAMP-mitogen-activated protein kinase pathway. Exp Mol Med. 2006;38:85–93. doi: 10.1038/emm.2006.10. [DOI] [PubMed] [Google Scholar]
  • [15].Mowa C.N., Usip S., Storey-Workley M., Amann R., Papka R. Substance P in the uterine cervix, dorsal root ganglia and spinal cord during pregnancy and the effect of estrogen on SP synthesis. Peptides. 2003;24:761–771. doi: 10.1016/S0196-9781(03)00120-7. [DOI] [PubMed] [Google Scholar]
  • [16].Winston J., Toma H., Shenoy M., Pasricha P.J. Nerve growth factor regulates VR-1 mRNA levels in cultures of adult dorsal root ganglion neurons. Pain. 2001;89:181–186. doi: 10.1016/S0304-3959(00)00370-5. [DOI] [PubMed] [Google Scholar]
  • [17].Reichardt L.F., Mobley W.C. Going the distance, or not, with neurotrophin signals. Cell. 2004;118:141–143. doi: 10.1016/j.cell.2004.07.008. [DOI] [PubMed] [Google Scholar]
  • [18].Donnerer J., Schuligoi R., Stein C. Increased content and transport of substance P and calcitonin gene-related peptide innervating inflammed tissue: evidence for a regulatory function of nerve growth factor in vivo. Neuroscience. 1992;49:693–698. doi: 10.1016/0306-4522(92)90237-V. [DOI] [PubMed] [Google Scholar]
  • [19].Schuligoi R., Amann R. Differential effects of treatment with nerve growth factor on thermal nociception and on calcitonin gene-related peptide content of primary afferent neurons in the rat. Neurosci Lett. 1998;252:147–149. doi: 10.1016/S0304-3940(98)00566-7. [DOI] [PubMed] [Google Scholar]
  • [20].McMahon S.B. NGF as a mediator of inflammatory pain. Philos Trans R Soc Lond B Biol Sci. 1996;351:431–440. doi: 10.1098/rstb.1996.0039. [DOI] [PubMed] [Google Scholar]
  • [21].Buck H., Winter J. K252a modulates the expression of Nerve Growth Factor-dependent capsaicin sensitivity and substance P levels in cultured adult rat dorsal root ganglion neurones. J Neurochem. 1996;67:345–351. doi: 10.1046/j.1471-4159.1996.67010345.x. [DOI] [PubMed] [Google Scholar]
  • [22].Malcangio M., Ramer M.S., Boucher T.J., McMahon S.B. Intrathecally injected neurotrophins and the release of substance P from the rat isolated spinal cord. Eur J Neurosci. 2000;12:139–144. doi: 10.1046/j.1460-9568.2000.00890.x. [DOI] [PubMed] [Google Scholar]
  • [23].Hu-Tsai M., Woolf C., Winter J. Influence of inflammation or disconnection from peripheral target tissue on the capsaicin sensitivity of rat dorsal root ganglion sensory neurons. Neurosci Lett. 1996;203:119–122. doi: 10.1016/0304-3940(95)12277-X. [DOI] [PubMed] [Google Scholar]
  • [24].McMahon S.B., Bennett D.L., Priestly J.V., Shelton D.L. The biological effects of endogenous nerve growth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule. Nat Med. 1995;1:774–780. doi: 10.1038/nm0895-774. [DOI] [PubMed] [Google Scholar]
  • [25].Bevan S., Winter J. Nerve Growth Factor (NGF) differentially regulates the chemosensitivity of adult rat cultured sensory neurons. J Neurosci. 1995;15:4918–4926. doi: 10.1523/JNEUROSCI.15-07-04918.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Lindsay R.M., Hammar A.J. Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature. 1989;337:362–364. doi: 10.1038/337362a0. [DOI] [PubMed] [Google Scholar]
  • [27].Malcangio M., Garrett N.E., Tomlinson D.R. Nerve growth factor treatment increases stimulus-evoked release of sensory neuropeptides in the rat spinal cord. Eur J Neurosci. 1997;9:1101–1104. doi: 10.1111/j.1460-9568.1997.tb01462.x. [DOI] [PubMed] [Google Scholar]
  • [28].Malcangio M., Garrett N.E., Tomlinson D.R. Nerve growth factor treatment enhances release of immunoreactive calcitonin gene-related peptide but not substance P from spinal dorsal horn slices in rats. Neurosci Lett. 2004;363:239–242. doi: 10.1016/j.neulet.2004.03.068. [DOI] [PubMed] [Google Scholar]
  • [29].Oh U., Hwang S.W., Kim D. Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons. J Neurosci. 1996;16:1659–1667. doi: 10.1523/JNEUROSCI.16-05-01659.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Hingtgen C.M., Waite K.J., Vasko M.R. Prostaglandins facilitate peptide release from rat sensory neurons by activating the adenosine 3′,5′-cyclic monophosphate transduction cascade. J Neurosci. 1995;15:5411–5419. doi: 10.1523/JNEUROSCI.15-07-05411.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Pei L., Lin C.Y., Dai J.P., Yin G.F. Facial pain induces the alteration of transient receptor potential vaniloid receptor 1 expression in rat trigeminal ganglion. Neurosci Bull. 2007;23:92–100. doi: 10.1007/s12264-007-0013-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Caterina J.M., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D., Julius D. The capsaicin-receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389:816–824. doi: 10.1038/39807. [DOI] [PubMed] [Google Scholar]
  • [33].Helliwell R.J.A., McLatchie L.M., Clarke M., Winter J., Bevan S., McIntyre P. Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia. Neurosci Lett. 1998;250:177–180. doi: 10.1016/S0304-3940(98)00475-3. [DOI] [PubMed] [Google Scholar]
  • [34].Skoff A.M., Resta C., Swamydas M., Adler J.E. Nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) regulate substance P release in adult spinal sensory neurons. Neurochem Res. 2003;28:847–854. doi: 10.1023/A:1023211107073. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES