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Spinal Opiate Analgesia pp 9–17Cite as

Theoretical Aspects and Practical Considerations Concerning Selective Opiate-Analgesia

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Summary

The observation of opiate binding in the substantia gelatinosa of the spinal cord, a region known to function in the modulation of sensory processing, and the observation that locally applied opiates would inhibit the discharge of nociceptive neurons, represents the substrate whereby animal and subsequent human investigations observed a powerful antinociceptive effect of spinally administered opiates.

The clinical use of spinal opiate action must be made on the basis of several considerations:

  1. 1.

    The superficially administered drugs must penetrate to the receptor sites lying within the spinal cord. Drugs which penetrate readily through lipid layers, will produce a more rapid onset and consequently will be more rapidly cleared. Drugs with low lipid-solubility will be characterized by a slow onset and a long duration of action. Polar agents will be less effective than lipid permeable agents following epidural administration.

  2. 2.

    The knowledge of how opiates exert their spinal effect give rise to certain partial considerations:

    1. a)

      It is known that the actions of opiates on the spinal cord are more potent against those inputs which arise from C-fibers, and will be less effective against acute pain, i.e. that of cutting, or perhaps acute distension and as observed in final stages of delivery.

    2. b)

      The specific analgetic effects of spinal opiates are made less specific by diffusion to supraspinal sites mediating respiratory and cardiovascular activity. The ability of lipid soluble drugs to diffuse into the vasculature makes it likely that such agents will produce higher blood levels.

    3. c)

      As the effects of opiates are mediated by an action on specific membrane receptors, the properties of the spinal effects will be defined by this receptor interaction. Thus, the effect should be dose dependent and subject to a similar structure activity relationship as that seen following peripherial administration and antagonized by naloxone.

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References

  1. Atweh SF, Kuhar MJ (1977) Autoradiographic localization of opiate receptors in rat brain, spinal cord and lower medulla. Brain Res 124:53

    Article  PubMed  CAS  Google Scholar 

  2. Behar M, Olshwang D, Magora F, Davidson JT (1979) Epidural morphine in treatment of pain. Lancet March 10:527

    Article  Google Scholar 

  3. Besson JM, Le Bars D, Oliveras J-L (1978) L’analgésie morphinique: données neurobiologiques. Ann Anaesth Franç 5:343

    Google Scholar 

  4. Besson JM, Wyon-Maillard MC, Benoist JM, Conseiller C, Hamann F (1973) Effect of phenoperidine on lamina V cells in the cat dorsal horn. J Pharmac Exp Ther 187:239

    CAS  Google Scholar 

  5. Bird SJ, Kuhar MJ (1976) The action of autoradiographically identified opiate receptor sites: a microiontophoretic study. Fed Proc 35:310

    Google Scholar 

  6. Bowsher D (1978) Pain pathways and mechanism. Anaesthesia 33:935

    Article  PubMed  CAS  Google Scholar 

  7. Bromage PR (1979) Subarachnoid and peridural anaesthesia. Lecture 209, ASA Annual Refresher Course Lectures Lipincott/Harper, Hagerstown

    Google Scholar 

  8. Bromage PR, Joyal AC, Binney JC (1963) Local anaesthetic drugs: penetration from the spinal extradural space into the neuraxis. Science 140:392

    Article  PubMed  CAS  Google Scholar 

  9. Calvillo O, Henry JL, Neuman RS (1974) Effects of morphine and naloxone on dorsal horn neurones in the cat. Can J Physiol Pharmacol 52:1207

    Article  PubMed  CAS  Google Scholar 

  10. Cervero F, Iggo A, Ogawa H (1976) Nociceptor driven dorsal horn neurons in the lumbar spinal cord of the cat. Pain 2:5

    Article  PubMed  CAS  Google Scholar 

  11. Chang K-J, Cuatrecasas P (1979) Different opiate receptor systems. J Biol Chem 254:2610

    PubMed  CAS  Google Scholar 

  12. Chiang CY, Liu JY, Chu T, Pai Y, Chang S (1975) Studies on spinal ascending pathways for effect of acupuncture analgesia in rabbit. Scientia Sinica 5:651

    Google Scholar 

  13. Coimbra A, Sodre-Borges BP, Magalhaes MM (1974) The substantia gelatinosa Rolandi of the rat. Fine structure, cytochemistry (acid phosphatase) and changes after dorsal root section. J Neurocytol 3:199

    Article  PubMed  CAS  Google Scholar 

  14. Corning JL (1885) Spinal anaesthesia and local medication of the cord. N Y med J 42:483

    Google Scholar 

  15. Cousins MJ, Mathers LE, Wilson PR, Graham JR (1979) Selective spinal analgesia. Lancet May 26:1141

    Article  Google Scholar 

  16. Davies GK, Tolhurst-Cleaver CL, James TL (1980) CNS depression from intrathecal morphine. Anesthesiology 52:280

    Article  PubMed  CAS  Google Scholar 

  17. Davies J (1978) Etudes électrophysiologiques des opiacés et des peptides endogènes sur les neurones centraux. Ann Anaesth Franç 5:399

    Google Scholar 

  18. De Castro J, DTnverno E, Lecron L, Levy D, Toppet-Balatoni E (1980) Perspective d’utilisation des morphinoides en anaesthésie loeorégionale. Anaest Analg Réanim 37:17

    Google Scholar 

  19. Denny-Brown D, Kirk EJ, Yanagisawa N (1973) The tract of Lissauer in relation to sensory transmission in the dorsal horn of the spinal cord in the macaque monkey. J comp Neurol 151:175

    Article  PubMed  CAS  Google Scholar 

  20. Fetz EE (1968) Pyramidal tracts effects on interneurons in the cat lumbar dorsal horn. J Neurophysiol 31:69

    PubMed  CAS  Google Scholar 

  21. Frederickson RCA, Schirmer EW, Griman EL, Harrell CE, Hewes CR (1976) Human endorphin: comparison with porcine endorphin, enkephaline and normorphine. Life Sci 19:1181

    Article  PubMed  CAS  Google Scholar 

  22. Giasi RM, D’Agostino E, Covino BG (1979) Absorption of Lidocaine following subarachnoid and epidural administration. Anaesth Analg 58:360

    Article  CAS  Google Scholar 

  23. Glynn CJ, Mathers LE, Cousins MJ, Wilson PR, Graham JR (1979) Spinal narcotics and respiratory depression. Lancet, Aug 18:356

    Article  Google Scholar 

  24. Göbel S (1974) Synaptic organization of the substantia gelatinosa glomeruli in the spinal trigeminal nucleus of the adult cat. J Neurocytol 3:219

    Article  PubMed  Google Scholar 

  25. Goldstein A, Lowery PJ (1975) Effect of opiate antagonist naloxone on body temperature in rats. Life Sci 17:927

    Article  PubMed  CAS  Google Scholar 

  26. Hamon M, Oliveras JL, Bourgoin S, Besson JM (1978) Anatomie des voies serotoninergiques bulbo- spinales chez le chat. Ann Anaesth Franç 5:319

    Google Scholar 

  27. Herz A (1978) Sites of opiate action in the central nervous system. In: Herz A (ed) Developments in opiate research. Marcel Dekker, New York, p 153

    Google Scholar 

  28. Hokfelt T, Ljungdahl A, Terenius L, Elde R, Nilsson G (1977) Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P. Proc Nat Acad Sci (Wash) 74:3081

    Article  CAS  Google Scholar 

  29. Hughes J, Smith T, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR (1975) Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258:577

    Article  PubMed  CAS  Google Scholar 

  30. Husemeyer RP, O’Connor MC, Davenport HT (1979) Aspects of epidural morphine. Lancet, Sept 15:383

    Google Scholar 

  31. Iwata N, Sakai Y (1971) Effect of fentanyl upon the spinal interneurons activated by Aδ-afferent fibres of the cutaneous nerve of the cat. Japan J Pharmacol 21:413

    Article  CAS  Google Scholar 

  32. Jessell TM, Iversen LL (1977) Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature (Lond) 268:549

    Article  CAS  Google Scholar 

  33. Kerr RWL (1975) Neuroanatomical substrates of nociception in the spinal cord. Pain 1:325

    Article  PubMed  CAS  Google Scholar 

  34. Kuhar M, Pert CB, Snyder SH (1973) Regional distribution of opiate receptor binding in monkey and human brain. Nature 245:447

    Article  PubMed  CAS  Google Scholar 

  35. La Motte C, Pert CB, Snyder SH (1976) Opiate receptor binding in primate spinal cord: distribution and changes after dorsal root section. Brain Res 112:407

    Article  Google Scholar 

  36. Le Bars D, Guilbaud G, Jurna I, Besson JM (1976) Differential effects of morphine on response of dorsal horn lamina V type cells elicited by A and C fibre stimulation in the spinal cat. Brain Res 115:518

    Article  PubMed  Google Scholar 

  37. Lembeck F (1953) Zur Frage der zentralen Übertragung afferenter Impulse. III. Mitteilung: Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks. Naunyn- Schmiedebergs Arch exp Path Pharmak 219:197

    CAS  Google Scholar 

  38. Leslie J, Camporesi E, Urban B, Bromage P (1979) Selective epidural analgesia. Lancet, July 21:151

    Google Scholar 

  39. Levante A, Albe-Fessard D, Thurel CL (1978) Données récentes sur les voies de la douleurs. Ann Anaesth Franç 5:301

    Google Scholar 

  40. Lilios A, Andereon FH (1979) Selective spinal analgesia. Lancet, August 18:357

    Article  Google Scholar 

  41. Magora F, Olshwang D, Eimerl D, Shorr J, Katzenelson R, Cotev S, Davidson JT (1980) Observations on extradural morphine analgesia in various pain conditions. Br J Anaesth 52:247

    Article  PubMed  CAS  Google Scholar 

  42. Mayer DJ, Liebeskind JC (1974) Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analyse. Brain Res 68:73

    Article  PubMed  CAS  Google Scholar 

  43. Melzack R, Wall PD (1965) Pain mechanism: a new theory. Science 150:971

    Article  PubMed  CAS  Google Scholar 

  44. Meyer GA, Fields HL (1972) Causalgia treated by selective large fibre stimulation of peripheral nerve. Brain 95:163

    Article  PubMed  CAS  Google Scholar 

  45. Müller H, Börner U, Stoyanov M, Gleumes L, Hempelmann G Peridurale Opiatapplikation bei Malignom bedingten, chronischen Schmerzen. Anaesth Intensivther Notfallmed (in press)

    Google Scholar 

  46. Müller H, Hempelmann G (1980) Lokal- und Leitungsanaesthesie. In: Voßschulte, Kümmerle, Peiper, Weller (eds) Lehrbuch der Chirurgie 7. Auflage, Thieme, Stuttgart (in press)

    Google Scholar 

  47. Perriss BW (1979) Epidural opiates in labour. Lancet, August 25:422

    Article  Google Scholar 

  48. Pert CB, Kuhar MJ, Snyder SH (1976) Opiate receptors: Autoradiographic localization in rat brain. Proc Nat Acad Sci USA 73:3729

    Article  PubMed  CAS  Google Scholar 

  49. Pomeranz B, Chiu D (1976) Naloxone blockade of acupuncture analgesia: Endorphins implicated. Life Sci 19:1757

    Article  PubMed  CAS  Google Scholar 

  50. Randic M, Miletic V (1977) Effect of substance P in cat dorsal horn neurones activated by noxious stimuli Brain Res 128:164

    Article  PubMed  CAS  Google Scholar 

  51. Rexed B (1953) A cytoarchitectonie atlas of the spinal cord in the cat. J comp Neurol 100:297

    Article  Google Scholar 

  52. Richardson DE (1976) Brain stimulation for pain control. Trans Biomed Eng 23:304

    Article  CAS  Google Scholar 

  53. Samii K, Feret J, Harari A, Viars P (1979) Selective spinal analgesia. Lancet, May 26:1142

    Google Scholar 

  54. Schleimer R, Benjamini E, Eisele J (1978) Pharmacokinetics of fentanyl as determined by radio- immunassay. Clin Pharmacol Ther 23:188

    PubMed  CAS  Google Scholar 

  55. Snyder SH (1977) Opiate receptors in the brain. New Engl J Med 296:266

    Article  PubMed  CAS  Google Scholar 

  56. Snyder SH (1977) Opiate receptors and internal opiates. Sci Am 236:44

    Article  PubMed  CAS  Google Scholar 

  57. Tagahashi T, Otsuka M (1975) Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section. Brain Res 87:1

    Article  Google Scholar 

  58. Teschemacher H (1978) Endogenous ligands of opiate receptors (Endorphins) In: Herz A (ed) Developments in opiate research. Marcel Dekker, New York, p 67

    Google Scholar 

  59. Teschemacher H personal communication

    Google Scholar 

  60. Terenius L, Wahlström A (1975) Morphine-like ligand for opiate receptors in human CSF. Life Sci 16:1759

    Article  CAS  Google Scholar 

  61. Urban BD (1973) Clinical observations suggesting a changing site of action during induction and regression of spinal and epidural anaesthesia. Anaesthesiology 39:496

    Article  CAS  Google Scholar 

  62. Von Cube B, Teschemacher H, Herz A, Hess R (1970) Permeation morphinartig wirksamer Substanzen an den Ort der aminorezeptiven Wirkung im Gehirn in Abhängigkeit von ihrer Liquorlöslichkeit nach intravenöser Applikation. Naunyn-Schmiedebergs Arch Pharmak 265:455

    Article  Google Scholar 

  63. Wang JK (1978) Soulangement de la douleur par injection intrathécale de sérotonine ou de morphine. Ann Anaesth Franç 5:371

    Google Scholar 

  64. Wang JK, Nauss LA, Thomas JE (1979) Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149

    Article  PubMed  CAS  Google Scholar 

  65. Wolfe MJ, Davies GK (1980) Analgesic action of extradural fentanyl. Br J Anaesth 52:357

    Article  PubMed  CAS  Google Scholar 

  66. Yaksh TL (1978) Inhibition by etorphine of the discharge of dorsal horn neurons: Effect on the neuronal response to both high- and low-threshold sensory input in the decerebrate spinal cat. Exp Neurol 60:23

    Article  PubMed  CAS  Google Scholar 

  67. Yaksh TL, Rudy TA (1976) Analgesia mediated by a direct spinal action of narcotics. Science 192:1357

    Article  PubMed  CAS  Google Scholar 

  68. Yaksh TL, Rudy TA (1977) Studies on the direct spinal action of narcotics in the production of analgesia in the rat. J Pharmacol exp Ther 202:411

    PubMed  CAS  Google Scholar 

  69. Zieglgänsberger W, Bayerl H (1976) The mechanism of inhibition of neuronal activity by opiate in the spinal cord of cat. Brain Res 115:111

    Article  PubMed  Google Scholar 

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Authors
  1. H. Müller
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  2. U. Börner
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  3. M. Stoyanov
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  4. G. Hempelmann
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Editor information

Editors and Affiliations

  1. Depts. of Neurologic Surgery and Pharmacology, Mayo Foundation, Rochester, MN, 55905, USA

    Tony L. Yaksh MD

  2. Dept. of Anesthesiology and Intensive Care Medicine, Justus Liebig University, Klinikstr. 29, D-6300, Giessen, Federal Republic of Germany

    Hermann Müller

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Müller, H., Börner, U., Stoyanov, M., Hempelmann, G. (1982). Theoretical Aspects and Practical Considerations Concerning Selective Opiate-Analgesia. In: Yaksh, T.L., Müller, H. (eds) Spinal Opiate Analgesia. Anaesthesiologie und Intensivmedizin Anaesthesiology and Intensive Care Medicine, vol 144. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-68261-2_2

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  • DOI: https://doi.org/10.1007/978-3-642-68261-2_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-11036-1

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