Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Dec 1;89(23):11617–11621. doi: 10.1073/pnas.89.23.11617

Marked increase in nitric oxide synthase mRNA in rat dorsal root ganglia after peripheral axotomy: in situ hybridization and functional studies.

V M Verge 1, Z Xu 1, X J Xu 1, Z Wiesenfeld-Hallin 1, T Hökfelt 1
PMCID: PMC50604  PMID: 1280832

Abstract

Using in situ hybridization, we studied nitric oxide (NO) synthase (EC 1.14.23.-) mRNA in lumbar dorsal root ganglia after peripheral transection of the sciatic nerve in rats. The effect of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester on the nociceptive flexor reflex was also studied in axotomized rats. Nerve section induced a dramatic increase in number of NO synthase mRNA-positive cells in the ipsilateral dorsal root ganglia. In some of these cells the peptides galanin and/or vasoactive intestinal polypeptide and/or neuropeptide Y were also strongly up-regulated. Intravenous administration of nitro-L-arginine methyl ester blocked spinal hyperexcitability at much lower dosages in axotomized than in normal animals. The results suggest involvement of NO in the function of lumbar sensory neurons, especially after axotomy, perhaps preferentially at peripheral sites.

Full text

PDF
11617

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aimi Y., Fujimura M., Vincent S. R., Kimura H. Localization of NADPH-diaphorase-containing neurons in sensory ganglia of the rat. J Comp Neurol. 1991 Apr 15;306(3):382–392. doi: 10.1002/cne.903060303. [DOI] [PubMed] [Google Scholar]
  2. Amara S. G., Arriza J. L., Leff S. E., Swanson L. W., Evans R. M., Rosenfeld M. G. Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide. Science. 1985 Sep 13;229(4718):1094–1097. doi: 10.1126/science.2994212. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Glatt C. E., Hwang P. M., Fotuhi M., Dawson T. M., Snyder S. H. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron. 1991 Oct;7(4):615–624. doi: 10.1016/0896-6273(91)90374-9. [DOI] [PubMed] [Google Scholar]
  4. Bredt D. S., Hwang P. M., Glatt C. E., Lowenstein C., Reed R. R., Snyder S. H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991 Jun 27;351(6329):714–718. doi: 10.1038/351714a0. [DOI] [PubMed] [Google Scholar]
  5. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  6. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bredt D. S., Snyder S. H. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A. 1989 Nov;86(22):9030–9033. doi: 10.1073/pnas.86.22.9030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brenneman D. E., Nicol T., Warren D., Bowers L. M. Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen. J Neurosci Res. 1990 Mar;25(3):386–394. doi: 10.1002/jnr.490250316. [DOI] [PubMed] [Google Scholar]
  9. Dagerlind A., Friberg K., Bean A. J., Hökfelt T. Sensitive mRNA detection using unfixed tissue: combined radioactive and non-radioactive in situ hybridization histochemistry. Histochemistry. 1992 Aug;98(1):39–49. doi: 10.1007/BF00716936. [DOI] [PubMed] [Google Scholar]
  10. Dawson T. M., Bredt D. S., Fotuhi M., Hwang P. M., Snyder S. H. Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7797–7801. doi: 10.1073/pnas.88.17.7797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Devor M., Govrin-Lippmann R. Axoplasmic transport block reduces ectopic impulse generation in injured peripheral nerves. Pain. 1983 May;16(1):73–85. doi: 10.1016/0304-3959(83)90087-8. [DOI] [PubMed] [Google Scholar]
  12. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  13. Garthwaite J., Garthwaite G., Palmer R. M., Moncada S. NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur J Pharmacol. 1989 Oct 17;172(4-5):413–416. doi: 10.1016/0922-4106(89)90023-0. [DOI] [PubMed] [Google Scholar]
  14. Haley J. E., Dickenson A. H., Schachter M. Electrophysiological evidence for a role of nitric oxide in prolonged chemical nociception in the rat. Neuropharmacology. 1992 Mar;31(3):251–258. doi: 10.1016/0028-3908(92)90175-o. [DOI] [PubMed] [Google Scholar]
  15. Hope B. T., Michael G. J., Knigge K. M., Vincent S. R. Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2811–2814. doi: 10.1073/pnas.88.7.2811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hökfelt T., Wiesenfeld-Hallin Z., Villar M., Melander T. Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci Lett. 1987 Dec 29;83(3):217–220. doi: 10.1016/0304-3940(87)90088-7. [DOI] [PubMed] [Google Scholar]
  17. Ignarro L. J., Byrns R. E., Buga G. M., Wood K. S. Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res. 1987 Dec;61(6):866–879. doi: 10.1161/01.res.61.6.866. [DOI] [PubMed] [Google Scholar]
  18. Jessell T., Tsunoo A., Kanazawa I., Otsuka M. Substance P: depletion in the dorsal horn of rat spinal cord after section of the peripheral processes of primary sensory neurons. Brain Res. 1979 May 25;168(2):247–259. doi: 10.1016/0006-8993(79)90167-7. [DOI] [PubMed] [Google Scholar]
  19. Larhammar D., Ericsson A., Persson H. Structure and expression of the rat neuropeptide Y gene. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2068–2072. doi: 10.1073/pnas.84.7.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morris R., Southam E., Braid D. J., Garthwaite J. Nitric oxide may act as a messenger between dorsal root ganglion neurones and their satellite cells. Neurosci Lett. 1992 Mar 16;137(1):29–32. doi: 10.1016/0304-3940(92)90290-n. [DOI] [PubMed] [Google Scholar]
  21. Nishizawa M., Hayakawa Y., Yanaihara N., Okamoto H. Nucleotide sequence divergence and functional constraint in VIP precursor mRNA evolution between human and rat. FEBS Lett. 1985 Apr 8;183(1):55–59. doi: 10.1016/0014-5793(85)80953-4. [DOI] [PubMed] [Google Scholar]
  22. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  23. Raivich G., Graeber M. B., Gehrmann J., Kreutzberg G. W. Transferrin Receptor Expression and Iron Uptake in the Injured and Regenerating Rat Sciatic Nerve. Eur J Neurosci. 1991;3(10):919–927. doi: 10.1111/j.1460-9568.1991.tb00027.x. [DOI] [PubMed] [Google Scholar]
  24. Shehab S. A., Atkinson M. E. Vasoactive intestinal polypeptide (VIP) increases in the spinal cord after peripheral axotomy of the sciatic nerve originate from primary afferent neurons. Brain Res. 1986 Apr 30;372(1):37–44. doi: 10.1016/0006-8993(86)91456-3. [DOI] [PubMed] [Google Scholar]
  25. Snyder S. H., Bredt D. S. Biological roles of nitric oxide. Sci Am. 1992 May;266(5):68-71, 74-7. doi: 10.1038/scientificamerican0592-68. [DOI] [PubMed] [Google Scholar]
  26. THOMAS E., PEARSE A. G. The fine localization of dehydrogenases in the nervous system. Z Zellforch Microsk Anat Histochem. 1961;2:266–282. doi: 10.1007/BF00736504. [DOI] [PubMed] [Google Scholar]
  27. Vincent S. R., Kimura H. Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience. 1992;46(4):755–784. doi: 10.1016/0306-4522(92)90184-4. [DOI] [PubMed] [Google Scholar]
  28. Vrontakis M. E., Peden L. M., Duckworth M. L., Friesen H. G. Isolation and characterization of a complementary DNA (galanin) clone from estrogen-induced pituitary tumor messenger RNA. J Biol Chem. 1987 Dec 15;262(35):16755–16758. [PubMed] [Google Scholar]
  29. Wakisaka S., Kajander K. C., Bennett G. J. Increased neuropeptide Y (NPY)-like immunoreactivity in rat sensory neurons following peripheral axotomy. Neurosci Lett. 1991 Apr 1;124(2):200–203. doi: 10.1016/0304-3940(91)90093-9. [DOI] [PubMed] [Google Scholar]
  30. Wall P. D., Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain. 1983 Dec;17(4):321–339. doi: 10.1016/0304-3959(83)90164-1. [DOI] [PubMed] [Google Scholar]
  31. Wall P. D., Gutnick M. Ongoing activity in peripheral nerves: the physiology and pharmacology of impulses originating from a neuroma. Exp Neurol. 1974 Jun;43(3):580–593. doi: 10.1016/0014-4886(74)90197-6. [DOI] [PubMed] [Google Scholar]
  32. Wall P. D., Woolf C. J. Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol. 1984 Nov;356:443–458. doi: 10.1113/jphysiol.1984.sp015475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wiesenfeld-Hallin Z., Xu X. J., Langel U., Bedecs K., Hökfelt T., Bartfai T. Galanin-mediated control of pain: enhanced role after nerve injury. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3334–3337. doi: 10.1073/pnas.89.8.3334. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES