Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-10T05:51:47.062Z Has data issue: false hasContentIssue false
  • English
  • Français

A Segmental Chronic Pain Syndrome in Rats Associated with Intrathecal Infusion of NMDA: evidence for selective action in the dorsal horn

Published online by Cambridge University Press:  18 September 2015

Douglas W. Zochodne ,
Marilyn Murray ,
Sukriti Nag  and
Richard J. Riopelle
Douglas W. Zochodne*
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta
Marilyn Murray
Affiliation:
Department of Medicine, Queen's University, Kingston, Ontario
Sukriti Nag
Affiliation:
Department of Pathology, Queen's University, Kingston, Ontario
Richard J. Riopelle
Affiliation:
Department of Medicine, Queen's University, Kingston, Ontario
*
University of Calgary, Department of Clinical Neurosciences and the Neuroscience Research Group, Division of Clinical Neurosciences, Heritage Medical Building, 3330 Hospital Drive N.W., Calgary, Alberta
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We explored the effects of chronic lumbar intrathecal NMDA infusion (mini-osmotic pumps) in Sprague-Dawley rats on motor and sensory axon integrity. Several different infusion protocols, each given over a 4 week period were examined: 0.15 M NMDA in phosphate buffered saline; phosphate buffered saline without NMDA; and 0.20 M magnesium sulfate plus 0.15 M NMDA; 0.35 M NMDA. In two additional protocols, 0.15 M NMDA or phosphate buffered saline were infused for a total of 8 weeks. Within 1-2 weeks of the onset of NMDA, but not phosphate buffered saline infusions, the rats exhibited irritability, circling, biting and excessive grooming resulting in loss of hair, and skin ulcerations from autotomy localized to lumbar and sacral innervated dermatomes. Co-infusion of NMDA with magnesium sulfate almost completely prevented these findings. The behavioural changes were not associated with abnormalities of sensory or motor conduction. Intrathecal infusion of NMDA induces a chronic “central” experimental pain disorder in rats, localized to the cord segment with the greatest exposure to the infusion, without involvement of peripheral sensory axons and sparing the axonal integrity of anterior horn cells.

Type
Articles
Information
Canadian Journal of Neurological Sciences , Volume 21 , Issue 1 , February 1994 , pp. 24 - 28
Copyright
Copyright © Canadian Neurological Sciences Federation 1994

References

REFERENCES

1.Wall, PD. Neuropathic pain and injured nerve: central mechanisms. Br Med Bull 1991; 47: 631–643.CrossRefGoogle ScholarPubMed
2.Aanonsen, LM, Lei, S, Wilcox, GL. Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord. Pain 1990; 41: 309–321.CrossRefGoogle ScholarPubMed
3.Dickenson, AH, Sullivan, AF. Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following C fibre stimulation. Neuropharmacology 1987; 26: 1235–1238.CrossRefGoogle ScholarPubMed
4.Willis, WD Jr, Coggeshall RE. Sensory Mechanisms of the Spinal Cord. Second Edition. 1991. New York, Plenum Press.CrossRefGoogle Scholar
5.Aanonsen, LM, Wilcox, GL. Nociceptive action of excitatory amino acids in the mouse: effects of spinally administered opioids, phencyclidine and sigma agonists. J Pharmacol Exp Ther 1987; 243: 9–19.Google ScholarPubMed
6.Sakurada, T, Tan-no, K, Manóme, Y, Sakurada, S, Kisara, K. Aversive response produced by intrathecal injection of NMDA in mice: effects of substance P and 5HT antagonists. In: Kameyama, T., Nabeshima, T., Domino, E.F. eds., NMDA Receptor Related Agents: Biochemistry, Pharmacology and Behaviour. Ann Arbor, MI. NPP Books; 1991: 219–225.Google Scholar
7.Nag, S, Riopelle, RJ. Spinal neuronal pathology associated with continuous intrathecal infusion of N-methyl-D-aspartate in the rat. Acta Neuropathol 1990; 81: 7–13.Google ScholarPubMed
8.Zochodne, DW, Ho, LT. The influence of indomethacin and guanethidine on experimental streptozotocin diabetic neuropathy. Can J Neurol Sci 1992; 19: 433–441.Google ScholarPubMed
9.Wall, PD, Gutnick, M. Properties of afferent nerve impulses originating from a neuroma. Nature 1974; 248: 740–743.CrossRefGoogle ScholarPubMed
10. Wall, PD, Devor, M. Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats. Pain 1983; 17: 321–339.CrossRefGoogle ScholarPubMed
11.Wall, PD, Devor, M, Inbal, R, et al. Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa. Pain 1979; 7: 103–113.CrossRefGoogle ScholarPubMed
12.Dubner, R, Ruda, MA. Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends Neurosci 1992; 15: 96–103.CrossRefGoogle ScholarPubMed
13.Greenamyre, JT, Young, AB, Penney, JB. Quantitative autoradio graphic distribution of L-[3-H] glutamate-binding sites in the rat central nervous system. J Neurosci 1984; 4: 2133–2144.CrossRefGoogle Scholar
14.Battaglia, G, Rustioni, A.Coexistence of glutamate and substance P in dorsal root ganglion neurons of the rat and monkey. J Comp Neurol 1988; 277: 302–312.CrossRefGoogle ScholarPubMed
15.Cahusac, PMB, Evans, RH, Hill, RG, Rodriquez, RE, Smith, DAS. The behavioral effects of an N-methylaspartate receptor antagonist following application to the lumbar spinal cord of conscious rats. Neuropharmacology 1984; 23: 719–724.CrossRefGoogle Scholar
16.Dougherty, PM, Willis, WD. Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of n-methyl-d-aspartic acid and substance P. Pain 1991; 47: 85–93.CrossRefGoogle ScholarPubMed
17.Murase, K, Ryu, PD, Randic, M. Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons. Neurosci Lett 1989; 103: 56–63.Google ScholarPubMed
18.Woodley, SJ, Kendig, JJ. Subsance P and NMDA receptors mediate a slow nocieptive ventral root potential in neonatal rat spinal cord. Brain Res 1991; 559: 17–21.CrossRefGoogle Scholar
19.Brown, WF. The Physiological and Technical Basis of Electromyography. Toronto Butterworth, 1984.Google Scholar
20.Teitelbaum, JS, Zatorre, RJ, Carpenter, S, et al. Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. N Engl J Med 1990; 322: 1781–1787.CrossRefGoogle Scholar