Effects of Somatostatin on the Responses of Rostrally Projecting Spinal Dorsal Horn Neurons to Noxious Stimuli in Cats

  • Jung, Sung-Jun (Department of Physiology, Kangwon National University College of Medicine) ;
  • Jo, Su-Hyun (Department of Physiology, Kangwon National University College of Medicine) ;
  • Lee, Sang-Hyuck (Department of Physiology, Kangwon National University College of Medicine) ;
  • Oh, Eun-Hui (Department of Physiology, Kangwon National University College of Medicine) ;
  • Kim, Min-Seok (Department of Orthopedics, Kangwon National University College of Medicine) ;
  • Nam, Woo-Dong (Department of Orthopedics, Kangwon National University College of Medicine) ;
  • Oh, Seog-Bae (Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University)
  • Published : 2008.10.31

Abstract

Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the $A{\delta}$ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and $A{\delta}$-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

Keywords

References

  1. Beitz AJ, Shepard RD, Wells WE. The periaqueductal gray- raphe magnus projection contains somatostatin, neurotensin and serotonin but not cholecystokinin. Brain Res 261: 132−137, 1983
  2. Carlton SM, Du J, Zhou S, Coggeshall RE. Tonic control of peripheral cutaneous nociceptors by somatostatin receptors. J Neurosci. 21: 4042−4049, 2001
  3. Chapman V, Dickenson AH. The effects of sandostatin and somatostatin on nociceptive transmission in the dorsal horn of the rat spinal cord. Neuropeptides 23: 147−152, 1992
  4. Chrubasik J, Meynadier J, Scherpereel P, Wünsch E. The effect of epidural somatostatin on postoperative pain. Anesth Analg 64: 1085−1088, 1985
  5. Dichter MA, Wang HL, Reisine T. Electrophysiological effects of somatostatin-14 and somatostatin-28 on mammalian central nervous system neurons. Metabolism 39: 86−90, 1990
  6. Fruhstorfer H, Zenz M, Notle H, Hensel H. Dissociated loss of cold and warm sensibility during regional anesthesia. Pflugers Arch 349: 73−82, 1974
  7. Gray DB, Pilar GR, Ford MJ. Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals. J Neurosci 9: 1683−1692, 1989
  8. Hanesch U, Heppelmann B, Schmidt RF. Somatostatin-like immunoreactivity in primary afferents of the medial articular nerve and colocalization with substance P in the cat. J Comp Neurol 354: 345−352, 1995
  9. Helmchen C, Fu Q-C, Sandkühler J. Inhibition of spinal nociceptive neurons by microinjections of somatostatin into the nucleus raphe magnus and midbrain periaqueductal gray of the anesthetized cat. Neurosci Lett 187: 137−141, 1995
  10. Helyes Z, Thán M, Oroszi G, Pintér E, Németh J, Kéri G, Szolcsányi J. Anti-nociceptive effect induced by somatostatin released from sensory nerve terminals and by synthetic somatostatin analogues in the rat. Neurosci Lett 278: 185−188, 2000
  11. Hunt SP, Kelly JS, Emson PC, Kimmel JR, Miller RJ, Wu JY. An immunohitochemical study of neuronal populations containing neuropeptides or GABA within the superficial layers of the rat dorsal horn. Neurosci. 6: 1883−1898, 1981
  12. Jiang N, Furue H, Katafuchi T, Yoshimura M. Somatostatin directly inhibits substantia gelatinosa neurons in adult rat spinal dorsal horn in vitro. Neurosci Res 47: 97−107, 2003
  13. Kamei J, Hitosugi H, Kasuya Y. Nociceptive responses to intrathecally administered substance P and somatostatin in diabetic mice. Life Sci 52: PL31−36, 1993
  14. Kamei J, Hitosugi H, Misawa M, Nagase H, Kasuya Y. Cold water swim stress inhibits the nociceptive responses to intrathecally administered somatostatin, but not substance P. Life Sci 52 PL169−174, 1993
  15. Kim SJ, Chung WH, Rhim H, Eun SY, Jung J, Kim J. Postsynaptic action mechanism of somatostatin on the membrane excitability in spinal substantia gelatinosa neurons of juvenile rats. Neurosci 114: 1139−1148, 2002
  16. Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig R. Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 353: 43−48, 1991
  17. Kuraishi Y, Hirota N, Sato Y, Hino Y, Satoh M, Takagi H. Evidence that substance P and somatostatin transmit separate information related to pain in the dorsal horn. Brain Res 325: 294−298, 1985
  18. Lu J, Ho RH. Evidence for dorsal root projection to somatostatin- immunoreactive structures in laminae I-II of the spinal dorsal horn. Brain Res Bull 28: 17−26, 1992
  19. Mather CS, Ho RH. Golgi impregnated somatostatin immunoreactive neurons in lamina II of the rat spinal cord. Brain Res Bull 28: 305−309, 1992
  20. Meynadier J, Chrubasik J, Dubar M, Wünsch E. Intrathecal somatostatin in terminally ill patients. A report of two cases. Pain 23: 9−12, 1985
  21. Millhorn DE, Seroogy K, Hökfelt T, Schmued LC, Terenius L, Buchan A, Brown JC. Neurons of the ventral medulla oblongata that contain both somatostatin and enkephalin immunoreactivities project to nucleus tractus solitarii and spinal cord. Brain Res. 424: 99−108, 1987
  22. Mollenholt P, Post C, Rawal N, Freedman J, Hökfelt T, Paulsson I. Antinociceptive and "neurotoxic" actions of somatostatin in rat spinal cord after intrathecal administration. Pain 32: 95−105, 1988
  23. Morton CR, Hutchison WD, Hendry IA, Duggan AW. Somatostatin: evidence for a role in thermal nociception. Brain Res 488: 89−96, 1989 https://doi.org/10.1016/0006-8993(89)90696-3
  24. Murase K, Nedeljkov V, Randic M. The actions of neuropeptides on dorsal horn neurons in the rat spinal cord slice preparation: an intracellular study. Brain Res 234: 170−176, 1982
  25. Ohno HY, Kuraishi M, Minami, Satoh M. Modality-specific antinociception produced by intrathecal injection of anti- somatostatin antiserum in rats. Brain Res 474: 197−200, 1988
  26. Paice JA, Penn RD, Kroin JS. Intrathecal octreotide for relief of intractable nonmalignant pain: 5-year experience with two cases. Neurosurgery 38: 203−207, 1996
  27. Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 20: 157−198, 1999
  28. Penn RD, Paice JA, Kroin JS. Octreotide: a potent new-non-opiate analgesic for intrathecal infusion. Pain 49: 13−19, 1992
  29. Pintér E, Helyes Z, Németh J, Pórszász R, Pethö G, Thán M, Kéri G, Horváth A, Jakab B, Szolcsányi J. Pharmacological characterisation of the somatostatin analogue TT-232: effects on neurogenic and non-neurogenic inflammation and neuropathic hyperalgesia. Naunyn Schmiedebergs Arch Pharmacol 366: 142-150, 2002 https://doi.org/10.1007/s00210-002-0563-9
  30. Rang HP, Bevan S, Dray A. Nociceptive peripheral neurons: cellular properties. In: Wall PD, Melzack R eds, Textbook of Pain. 3rd ed. Churchill Livingstone, Edinburgh (UK), p 57-78, 1994
  31. Robbins R. Somatostatin and the cerebral cortex. In: Patel YC, Tanneum GS eds, Somatostatin, Plenum, New York, p 201-216, 1985
  32. Sandkühler J, Fu Q-G, Helmchen C. Spinal somatostatin superfusion in vivo affects activity of cat nociceptive dorsal horn neurones: Comparison of spinal morphine. Neurosci 34: 565-576, 1990 https://doi.org/10.1016/0306-4522(90)90165-Z
  33. Sandle GI, Warhurst G, Butterfield I, Higgs NB, Lomax RB. Somatostatin peptides inhibit basolateral potassium channels in human colonic crypts. Am J Physiol 277: G967-975, 1999
  34. Seybold VS, Hylden JLK, Wilcox GL. Intrathecal substance P and somatostatin in rats: Behaviors indicative of sensation. Peptides 3: 49-54, 1982 https://doi.org/10.1016/0196-9781(82)90141-3
  35. Sicuteri F, Geppetti P, Marabini S, Lembeck F. Pain relief by somatostatin in attacks of cluster headache. Pain 18: 359-365, 1984 https://doi.org/10.1016/0304-3959(84)90048-4
  36. Simone DA, Kajander KC. Responses of cutaneous A-fiber nociceptors to noxious cold. J. Neurophysiol 77: 2049-2060, 1997 https://doi.org/10.1152/jn.1997.77.4.2049
  37. Song P, Hu JY, Zhao ZQ. Spinal somatostatin SSTR2A receptors are preferentially up-regulated and involved in thermonociception but not mechanonociception. Exp Neurol 178: 280-287, 2002 https://doi.org/10.1006/exnr.2002.8025
  38. Stine SM, Yang HY, Costa E. Evidence for ascending and descending intraspinal as well as primary sensory somatostatin projections in the rat spinal cord. J Neurochem 38: 1144-1150, 1982 https://doi.org/10.1111/j.1471-4159.1982.tb05361.x
  39. Taddese A, Nah SY, McClesky EW. Selective opioid inhibition of small nociceptive neurons. Science 270: 1366-1369, 1995 https://doi.org/10.1126/science.270.5240.1366
  40. Traub RJ, Brozoski D. Anti-somatostatin antisera, but neither a somatostatin agonist (octreotide) nor antagonist (CYCAM), attenuates hyperalgesia in the rat. Peptides 17: 769-773, 1996 https://doi.org/10.1016/0196-9781(96)00112-X
  41. Tsai YC, So EC, Chen HH, Wang LK, Chien CH. Effect of intrathecal octreotide on thermal hyperalgesia and evoked spinal c-Fos expression in rats with sciatic constriction injury. Pain 99: 407-413, 2002 https://doi.org/10.1016/S0304-3959(02)00107-0
  42. Tuchscherer MM, Seybold VS. Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat. Neurosci 14: 593-605, 1985 https://doi.org/10.1016/0306-4522(85)90313-6
  43. Wang H, Bogen C, Reisine T, Dichter M. SRIF-14 and SRIF-28 induce opposite effects on potassium currents in rat neocortical neurons. Proc Natl Acad Sci USA 86: 9616-9620, 1989
  44. Wiesenfeld-Hallin Z. Intrathecal somatostatin modulates spinal sensory and reflex mechanisms: behavioral and electrophysiological studies in the rat. Neurosci Lett 62: 69-74, 1985 https://doi.org/10.1016/0304-3940(85)90286-1
  45. Wiesenfeld-Hallin Z. Substance P and somatostatin modulate spinal cord excitability via physiologically different sensory pathways. Brain Res 372: 172-175, 1986 https://doi.org/10.1016/0006-8993(86)91473-3
  46. Willis WD, Coggeshall RE. The sensory channel. In: Willis WD, Coggeshall RE eds, Sensory Mechanisms of the Spinal Cord. 2nd ed. Plenum Press, New York, p 449-456, 1991
  47. Yajiri Y, Yoshimura M, Okamoto M, Takahashi H, Higashi H. A novel slow excitatory postsynaptic current in substantia gelatinosa neurons of the rat spinal cord in vitro. Neurosci 76: 673-688, 1997 https://doi.org/10.1016/S0306-4522(96)00291-6