Skip to main content
SpringerLink
Log in

Cardiac nociception in rats

Neuronal pathways and the influence of dermal neurostimulation on conveyance to the central nervous system

  • Original Articles
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Neurostimulation for refractory angina pectoris is often advocated for its clinical efficacy. However, the recruited pathways to induce electroanalgesia are partially unknown. Therefore, we sought to study the effect of neurostimulation on experimentally induced cardiac nociception, using capsaicin as nociception-induced substance. Four different groups of male Wistar rats were pericardially infused with either saline or capsaicin with or without neurostimulation. Group StimCap was infused with capsaicin, and group StimVeh was infused with saline. Both groups were treated with neurostimulation. Group ShamCap was only infused with capsaicin without stimulation, whereas group ShamVeh was only infused with saline. Neuronal activation differences were assessed with cytochemical staining, revealing the cellular expression of c-fos. Pain behavior was registered on video and was quantitatively analyzed. In the StimCap and ShamCap groups, all animals exerted typical pain behavior, whereas in the StimVeh group only moderate changes in behavior were observed. Group ShamVeh animals were unaffected by the procedure. The upper thoracic spinal cord showed high numbers of c-fos-positive cells, predominately in laminae III and IV in both StimCap and StimVeh groups. Almost no c-fos expression was noticed in groups ShamCap and ShamVeh in these sections of the spinal cord. In groups StimCap and ShamCap a significantly higher number of c-fos-positive cells in comparison with groups StimVeh and ShamVeh were noticed in the periambigus region, the nucleus tractus solitarius, and the paraventricular hypothalamus. In the paraventricular thalamus, periaqueductal gray, and central amygdala, no significant differences were noted among the first three groups, and the c-fos concentration in these three groups was significantly higher than in group ShamVeh. It is concluded that neurostimulation does not influence capsaicin-induced cardiac nociceptive pain pulses to the central nervous system. Furthermore, capsaicin-induced cardiac pain and neurostimulation may utilize two different pathways.

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

Similar content being viewed by others

References

  • Ammons W.S., Girardot M.-N., and Foreman R. D. (1985a) T2–T5 spinothalamic neurons projecting to medial thalamus with viscerosomatic input. J. Neurophysiol. 54, 73–89.

    PubMed  CAS  Google Scholar 

  • Ammons W. S., Girardot M.-N., and Foreman R. D. (1985) Effects of intracardiac bradykinin on T2–T5 medial spinothalamic cells. Am. J. Physiol. 249, R147-R152.

    PubMed  CAS  Google Scholar 

  • Anderson C., Hole P., and Oxhoj H. (1994) Does pain relief with spinal cord stimulation for angina conceal myocardial infarction? Br. Heart J. 71, 419–421.

    Google Scholar 

  • Anton F., Herdegen T., Peppel P., and Leah J. D. (1991) C-fos-like immunoreactivity in rat brain stem neurons following noxious chemical stimulation of the nasal mucosa. Neuroscience 41, 629–641.

    Article  PubMed  CAS  Google Scholar 

  • Apkarian A. V. and Hodge C. J. (1989) Primate spinothalamic pathways II. The cells of origin of the dorsolateral and ventral spinothalamic pathways. J. Comp. Neurol. 288, 474–492.

    Article  PubMed  CAS  Google Scholar 

  • Baker D. G., Coleridge H. M., Coleridge J. C. G., and Nerdrum T. (1980) Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of cat. J. Physiol. 306, 519–536.

    PubMed  CAS  Google Scholar 

  • Berendse H. W. and Groenewengen V. H. (1991) Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat. Neuroscience 42, 73–102.

    Article  PubMed  CAS  Google Scholar 

  • Blair R. W., Weber R. N., and Foreman R. D. (1981) Characteristics of primate spinothalamic tract neurons receiving viscerosomatic convergent inputs in T3–T5 segments. J. Neurophysiol. 46, 797–811.

    PubMed  CAS  Google Scholar 

  • Blair R. W., Weber R. N., and Foreman R. D. (1982) Responses of thoracic spinothalamic neurons to intracardiac injection of bradykinin in the monkey. Circ. Res. 51, 83–94.

    PubMed  CAS  Google Scholar 

  • Brüggemann J., Shi T., and Apkarian A. V. (1997) Viscerosomatic neurons in the primary somatosensory cortex (SI) of the squirrel monkey. Brain Res. 756(1–2), 297–300.

    Article  PubMed  Google Scholar 

  • Casey K. L. and Jones E. G. (1978) Supraspinal mechanisms: an overview of ascending pathways: brainstem and thalamus. Neurosci. Res. Prog. Bull. 16, 103–118.

    Google Scholar 

  • Chandler M. J. and Foreman R. D. (1997) Pathways and characterization of excitatory cardiopulmonary sympathetic afferent (CPSA) input to ventroposterolateral (VPL) thalamic cells in primates. Soc. Neurosci. 23(2), 9151.

    Google Scholar 

  • Chandler M. J., Hobbs S. F., Fu Q.-G., Kenshalo D. R., Blair R. W., and Foreman R. D. (1992) Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distention. Brain Res. 571, 26–34.

    Article  PubMed  CAS  Google Scholar 

  • Coleridge H. M. and Coleridge J. C. G. (1980) Cardiovascular afferents involved in regulation of peripheral vessels. Annu. Rev. Physiol. 42, 413–427.

    Article  PubMed  CAS  Google Scholar 

  • Colin I., Clement, K. Keay A., Podzbenko K, Gorden B. D., and Bandler R. (2000) Spinal Sources of noxious visceral and noxious deep somatic afferent drive onto the ventrolateral periaqueductal gray of the rat. J. Comp. Neurol. 425, 323–344.

    Article  Google Scholar 

  • De Jongste M. J. L., Hautvast R. W. M., Ruiters M. H. J., and Ter Horst G. J. (1998). Spinal cord stimulation and the induction of c-fos and heat shock protein in the central nervous system of rats. Neuromodulation 1, 66–77.

    Google Scholar 

  • Dragunow M. and Faull R. (1989) The use of c-fos as a metabolic marker in neuronal pathway tracing. J. Neurosci. Methods 29, 261–265.

    Article  PubMed  CAS  Google Scholar 

  • Follett K. A. and Dirks B. (1994) Characterization of responses of primary somatosensory cerebral cortex neurons to noxious visceral stimulation in the rat. Brain Res. 656(1), 27–32.

    Article  PubMed  CAS  Google Scholar 

  • Foreman R. D. (1999) Mechanisms of cardiac pain. Annu. Rev. Physiol. 61, 143–167.

    Article  PubMed  CAS  Google Scholar 

  • Gybels J. M. and Sweet W. H., eds. (1989) Neurosurgical Treatment of Persistent Pain. Karge, New York.

    Google Scholar 

  • Harris J. A. (1998) Using c-fos as a neural marker of pain. Brain Res. Bull. 45(1), 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Holzer P. (1991) Capsaicin: cellular targets, mechanisms of action and selectivity for thin sensory neurons. Pharmacol. Rev. 11, 330–343.

    Google Scholar 

  • Hautvast R. W. M., Ter Horst G. J., De Jong B. M., De Jongste M. J. L., Blanksma P. K., Paans A. M. J., and Korf J. (1997) Relative changes in regional cerebral blood flow during spinal cord stimulation in patient with refractory angina pectoris. Eur. J. Neurosci. 9, 1178–1183.

    Article  PubMed  CAS  Google Scholar 

  • Hautvast R. W., Brouwer J., DeJongste M. J., and Lie K. I. (1998) Effect of spinal cord stimulation on heart rate variability and myocardial ischemia in patients with chronic intractable angina pectoris—a prospective ambulatory electrocardiographic study. Clin. Cardiol. 21(1), 33–38.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Jessurun G. A., DeJongste M. J., and Blanksma P. K. (1996) Current views on neurostimulation in the treatment of cardiac ischemic syndromes. Pain 66, 109–116.

    Article  PubMed  CAS  Google Scholar 

  • Kemper R. H., Meijler W. J., Ter Horst G. J. (1997) Trigeminovascular stimulation in conscious rats. Neuroreport. 8(5), 1123–1126.

    Article  PubMed  CAS  Google Scholar 

  • Kuo D. C., Oravitz J., and De Groet W. C. (1984) Tracing of afferent and efferent pathways in the left inferior cardiac nerve of the cat using retrograde and transganglionic transport of horseradish peroxidase. Brain Res. 321, 111–118.

    Article  PubMed  CAS  Google Scholar 

  • Lewis T. (1942) Pain. McMillan, London, UK, 1942.

    Google Scholar 

  • Lombardi F., Della Bella P., Casati R., and Malliani A. (1981) Effects of intracoronary administration of bradykinin on the impulse activity of afferent sympathetic unmyelinated fibers with left ventricular endings in the cat. Circ. Res. 48, 69–75.

    PubMed  CAS  Google Scholar 

  • Maggi C. A., Giuliani S., Meini S., Santicioli P. (1995) Calcitonin gene related peptide as inhibitory neurotransmitter in the ureter. Can. J. Physiol. Pharmacol. 73(7), 986–990.

    PubMed  CAS  Google Scholar 

  • Mannheimer C., Carlsson C. A., Emanuelsson H., Vedin A., Waagstein F., Wilhelmsson C. (1985) The effects of transcutaneous electrical nerve stimulation in patients with severe angina pectoris. Circulation 71(2), 308–316.

    PubMed  CAS  Google Scholar 

  • Meller S. T. and Gebhart G. F. (1992) A critical review of the afferent pathways and the potential chemical mediators involved in cardiac pain. Neuroscience 48, 501–524.

    Article  PubMed  CAS  Google Scholar 

  • Melzack R. and Wall P. D. (1982) The Challenge of Pain. Basic Books, New York.

    Google Scholar 

  • Nowicki D. and Szulczyk P. (1986) Longitudinal distribution of negative cord dorsum potentials following stimulation of afferent fibres in the left inferior cardiac nerve. J. Auton. Nerv. Syst. 18, 185–197.

    Article  Google Scholar 

  • Pagani M., Pizzinelli P., Furlan R., Guzzetti S., and Rimoldi O. (1985) Analysis of the pressor sympathetic reflex produced by intracoronary injections of bradykinin in conscious dogs. Circ. Res. 56, 175–183.

    PubMed  CAS  Google Scholar 

  • Rosen S. D. and Camici P. G. (2000) The brain-heart axis in the perception of cardiac pain: the elusive link between ischemia and pain. Ann. Med. 32(5), 350–364.

    PubMed  CAS  Google Scholar 

  • Rosen S. D., Paulesu E., Frith C. D., Frackowiak R. S. J., Jomes T., and Camici P. G. (1994) Central nervous pathways mediating angina pectoris. Lancet 344, 147–150.

    Article  PubMed  CAS  Google Scholar 

  • Rosen S. D., Paulesu E., Nihoyannopoulos P., Tousoulis D., Frackowiak R. S. J., Firth C. D., et al. (1996) Silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia. Ann. Intern. Med. 124, 939–949.

    PubMed  CAS  Google Scholar 

  • Sadikot A. F., Parent A., and Francois C. (1990) The center median and parafascicular thalamic nuclei project respectively to the sensorimotor and associate limbic striatal territories in the squirrel monkey. Brain Res. 510, 161–165.

    Article  PubMed  CAS  Google Scholar 

  • Sagar S. M., Sharp F. R., and Curran T. (1988) Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science 240, 1328–1331.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Sugiura Y., Terul N., and Hosoya Y. (1989) Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers. J. Neurophysiol. 62, 834–840.

    PubMed  CAS  Google Scholar 

  • Swanson L. W. (1992) Brain maps: computer graphic files. Elsevier Science Publisher, Amsterdam, The Netherlands.

    Google Scholar 

  • Szolcsanyi J. (1993) Actions of capsaicin on sensory receptors, in Capsaicin in the Study of Pain (Wood J., ed.), Academic, London, pp. 1–26.

    Google Scholar 

  • Szolcsanyi J. (1996) Capsaicin-sensitive sensory nerves terminals with local and systemic efferent functions: facts and scopes of the unorthodox neuroregulatory mechanism. Prog. Brain Res. 113, 343–359.

    Article  PubMed  CAS  Google Scholar 

  • Szolcsanyi J., Oroszi G., Nemeth J., Szilvassy Z., Blasig I. E., and Tosaki A. (2001) Functional and biochemical evidence of capsaicin-induced neural endothelin release in isolated working rat heart. Eur. J. Pharmacol. 419(2–3), 215–221.

    Article  PubMed  CAS  Google Scholar 

  • Vance W. H. and Bouker R. C. (1983) Spinal origins of cardiac afferents from the region of the left anterior descending artery. Brain Res. 258, 96–100.

    Article  Google Scholar 

  • Vierck C. J., Greenspan J. D., Ritz L. A., and Yeomans D. C. (1986) The spinal pathways contributing to the ascending conduction and the descending modulation of pain sensations and reactions, in Spinal Afferent Processing (Yaksh T. L., ed.), Plenum, New York, pp. 275–329.

    Google Scholar 

  • Willis W. and Coggeshall R. (1991) Sensory Mechanisms of the Spinal Cord, 2nd ed., Plenum, New York.

    Google Scholar 

  • Zhang R., Cai K., Na J., Ma X., Liu S., Wang H., and Teng G. (1991) Effects of stimulating periaqueductal gray on the nociceptive neuron discharges of post-thalamic nucleus evoked by stimulation of splanchnic nerve in cats. Zhen Ci Yan Jiu 16(1), 10–14.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medical Sciences, Groningen, The Netherlands

    Ibrahim A. M. Albutaihi

  2. Department of Cardiology, Thoraxcenter, Groningen, The Netherlands

    Raymond W. M. Hautvast & Mike J. L. DeJongste

  3. Biological Psychiatry, Groningen, The Netherlands

    Gert J. Ter Horst

  4. Neurosurgery, Groningen, The Netherlands

    Michiel J. Staal

Authors
  1. Ibrahim A. M. Albutaihi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raymond W. M. Hautvast
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mike J. L. DeJongste
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gert J. Ter Horst
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michiel J. Staal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mike J. L. DeJongste.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Albutaihi, I.A.M., Hautvast, R.W.M., DeJongste, M.J.L. et al. Cardiac nociception in rats. J Mol Neurosci 20, 43–52 (2003). https://doi.org/10.1385/JMN:20:1:43

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:20:1:43

Index Entries

Search

Navigation