Pathophysiology of Compressive Radiculopathy

Czech version

Authors: R. Jančálek ^1,2; P. Dubový ²; Z. Novák ¹
Authors‘ workplace: Ne urochirurgická klinika LF MU a FN u sv. Anny v Brně ¹; Oddělení ne uro anatomi e Anatomického ústavu LF MU, Brno ²
Published in: Cesk Slov Neurol N 2008; 71/104(4): 405-413
Category: Review Article

Podporováno granty GAČR 309/ 07/ 0121 a MSM0021622404.

Overview

A relati onship between compressi on of the spinal ro ots and radiculopathy was described by Mixter and Barr in 1934. However, the compressi on of an intact spinal ro ot le ads only to paraesthesi a and does not explain the inducti on of radicular ne uropathic pain. Recent experimental and clinical studi es de aling with the discogenic eti ology of radiculopathy have documented the essenti al role of an inflammatory re acti on for the inducti on of clinical symptomatology. Therefore, the pathophysi ology of compressi on radiculopathy may be considered multifactori al. A mechanical effect during compressi on of the spinal ro ots le ads to changes of blo od supply and direct injury to nervo us tissue. Changes of connective tissue with endone uri al fibrosis prevail during chronic compressi on. An injury to the spinal ro ots also le ads to rele ase of pro inflammatory cytokines and the invasi on of macrophages. The prolapsed tissue of the intervertebral disc can also play an active role in the formati on of a pro- inflammatory environment. The inflammatory re acti on cre ates the conditi ons that ca use irritati on of the spinal ro ots and inducti on of the radicular ne uropathic pain. An accurate understanding of both the mechanical and the inflammatory roles in compressi on radiculopathy allows selecti on of an optimal tre atment strategy.

Key words:
spinal ro ot – compressi on – vascular supply – inflammati on – macrophage – cytokine

Sources

1. Boden SD, Davis DO, Dina TS, Patronas NJ, Wi esel SW. Abnormal magnetic- resonance scans of the lumbar spine in asymptomatic subjects. A prospective investigati on. J Bone Jo int Surg Am 1990; 72(3): 403– 408.

2. Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 1934; 211: 210– 215.

3. Jancalek R, Dubovy P. An experimental animal model of spinal ro ot compressi on syndrome: an analysis of morphological changes of myelinated axons during compressi on radiculopathy and after decompressi on. Exp Brain Res 2007; 179(1): 111– 119.

4. Dray A. Inflammatory medi ators of pain. Br J Anaesth 1995; 75(2): 125– 131.

5. Smith SA, Massi e JB, Chesnut R, Garfin SR. Straight leg raising. Anatomical effects on the spinal nerve ro ot witho ut and with fusi on. Spine 1993; 18(8): 992– 999.

6. Kobayashi S, Shizu N, Suzuki Y, Asai T, Yoshizawa H. Changes in nerve ro ot moti on and intraradicular blo od flow during an intraoperative straight- leg- raising test. Spine 2003; 28(13): 1427– 1434.

7. Petterson CA, Olsson Y. Blo od supply of spinal nerve ro ots. An experimental study in the rat. Acta Ne uropathol 1989; 78(5): 455– 461.

8. Nordin M, Nyström B, Wallin U, Hagbarth KE. Ectopic sensory discharges and paresthesi ae in pati ents with disorders of peripheral nerves, dorsal ro ots and dorsal columns. Pain 1984; 20(3): 231– 245.

9. Olmarker K, Rydevik B, Holm S, Bagge U.Effects of experimental graded compressi on on blo od flow in spinal nerve ro ots. A vital microscopic study on the porcine ca uda equina. J Orthop Res 1989; 7(6): 817– 823.

10. Pedowitz RA, Garfin SR, Massi e JB, Hargens AR, Swenson MR, Myers RR et al. Effects of magnitude and durati on of compressi on on spinal nerve ro ot conducti on. Spine 1992; 17(2): 194– 199.

11. Jančálek R, Dubový P. Možné morfologické a patofyziologické podklady vzniku neuropatické bolesti. Cesk Slov Ne urol N 2004; 67/ 100(1): 6– 11.

12. McLachlan EM, Janig W, Devor M,Michaelis M. Peripheral nerve injury triggers noradrenergic spro uting within dorsal ro ot gangli a. Nature 1993; 363(6429): 543– 546.

13. Dubovy P, Jancalek R, Klusakova I. A heterogeneo us immunofluorescence staining for laminin‑1 and related basal lamina molecules in the dorsal ro ot gangli a following constricti on nerve injury. Histochem Cell Bi ol 2006; 125(6): 671– 680.

14. Devor M, Dubner R. Centrifugal activity in afferent C fibers influences the spontaneo us afferent barrage generated in nerve end ne uromas. Brain Res 1988; 446(2): 396– 400.

15. Kayama S, Konno S, Olmarker K, Yabuki S, Kikuchi S. Incisi on of the anulus fibrosus induces nerve ro ot morphologic, vascular, and functi onal changes. An experimental study. Spine 1996; 21(22): 2539– 2543.

16. Tolonen J, Gronblad M, Virri J, Seitsalo S, Rytömaa T, Karaharju E. Transforming growth factor beta receptor inducti on in herni ated intervertebral disc tissue: an immunohistochemical study. Eur Spine J 2001; 10(2): 172– 176.

17. Nagano T, Yonenobu K, Miyamoto S, Tohyama M, Ono K. Distributi on of the basic fibroblast growth factor and its receptor gene expressi on in normal and degenerated rat intervertebral discs. Spine 1995; 20(18): 1972– 1978.

18. Bobechko WP, Hirsch C. Auto- Immune Response to Nucle us Pulposus in the Rabbit. J Bone Jo int Surg Br 1965; 47: 574– 580.

19. McCarron RF, Wimpee MW, Hudkins PG, Laros GS. The inflammatory effect of nucle us pulposus. A possible element in the pathogenesis of low- back pain. Spine 1987; 12(8): 760– 764.

20. Specchi a N, Pagnotta A, Toesca A, Greco F. Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine. Eur Spine J 2002; 11(2): 145– 151.

21. Geiss A, Larsson K, Rydevik B, Takahashi I, Olmarker K. Auto immune properti es of nucle us pulposus: an experimental study in pigs. Spine 2007; 32(2): 168– 173.

22. Kawaguchi S, Yamashita T, Yokogushi K, Murakami T, Ohwada O, Sato N. Immunophenotypic analysis of the inflammatory infiltrates in herni ated intervertebral discs. Spine 2001; 26(11): 1209- 1214.

23. Saksela O, Rifkin DB. Rele ase of basic fibroblast growth factor-heparan sulfate complexes from endotheli al cells by plasminogen activator-medi ated proteolytic activity. J Cell Bi ol 1990; 110(3): 767– 775.

24. Do ita M, Kanatani T, Harada T, Mizuno K. Immunohistologic study of the ruptured intervertebral disc of the lumbar spine. Spine 1996; 21(2): 235– 241.

25. Nygaard OP, Mellgren SI, Osterud B. The inflammatory properti es of contained and noncontained lumbar disc herni ati on. Spine 1997; 22(21): 2484– 2488.

26. Dubovy P, Jancalek R, Klusakova I, Svizenska I, Pejchalova K. Intra- and extrane uronal changes of immunofluorescence staining for TNF‑alpha and TNFR1 in the dorsal ro ot gangli a of rat peripheral ne uropathic pain models. Cell Mol Ne urobi ol 2006; 26(7– 8): 1205– 1217.

27. Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kaki uchi T. Inflammatory cytokines in the herni ated disc of the lumbar spine. Spine 1996; 21(2): 218– 224.

28. Miyamoto H, Sa ura R, Harada T, Do ita M, Mizuno K. The role of cyclo oxygenase- 2 and inflammatory cytokines in pain inducti on of herni ated lumbar intervertebral disc. Kobe J Med Sci 2000; 46(1– 2): 13– 28.

29. Sommer C, Petra usch S, Lindenla ub T, Toyka KV. Ne utralizing antibodi es to interle ukin 1- receptor reduce pain associ ated behavi or in mice with experimental ne uropathy. Ne urosci Lett 1999; 270(1): 25– 28.

30. Aoki Y, Rydevik B, Kikuchi S, Olmarker K. Local applicati on of disc- related cytokines on spinal nerve ro ots. Spine 2002; 27(15): 1614– 1617.

31. Olmarker K, Larsson K. Tumor necrosis factor alpha and nucle us- pulposus‑induced nerve ro ot injury. Spine 1998; 23(23): 2538– 2544.

32. Wagner R, Myers RR. Endone uri al injecti on of TNF‑alpha produces ne uropathic pain behavi ors. Ne uroreport 1996; 7(18): 2897– 2901.

33. Schäfers M, Geis C, Svensson CI, Luo ZD, Sommer C. Selective incre ase of tumo ur necrosis factor‑alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sci atic nerve. Eur J Ne urosci 2003; 17(4): 791– 804.

34. Sommer C, Lindenla ub T, Te uteberg P, Schafers M, Hartung T, Toyka KV. Anti‑TNF‑ne utralizing antibodi es reduce pain‑related behavi or in two different mo use models of painful monone uropathy. Brain Res 2001; 913(1): 86– 89.

35. Hattori A, Tanaka E, Murase K, Ishida N, Chatani Y, Tsujimoto M et al. Tumor necrosis factor stimulates the synthesis and secreti on of bi ologically active nerve growth factor in non- ne uronal cells. J Bi ol Chem 1993; 268(4): 2577– 2582.

36. Shu XQ, Mendell LM. Ne urotrophins and hyperalgesi a. Proc Natl Acad Sci U S A 1999; 96(14): 7693– 7696.

37. Kerr BJ, Bradbury EJ, Bennett DL, Trivedi PM, Dassan P, French J et al. Brain‑derived ne urotrophic factor modulates nociceptive sensory inputs and NMDA- evoked responses in the rat spinal cord. J Ne urosci 1999; 19(12): 5138– 5148.

38. Wo olf CJ, Safi eh- Garabedi an B, Ma QP, Crilly P, Winter J. Nerve growth factor contributes to the generati on of inflammatory sensory hypersensitivity. Ne urosci ence 1994; 62(2): 327– 331.

39. Kawakami M, Matsumoto T, Tamaki T. Roles of thromboxane A2 and le ukotri ene B4 in radicular pain induced by herni ated nucle us pulposus. J Orthop Res 2001; 19(3): 472– 477.

40. Kang JD, Georgescu HI, McIntyre- Larkin L, Stefanovic- Racic M, Donaldson WF 3rd, Evans CH. Herni ated lumbar intervertebral discs spontaneo usly produce matrix metalloproteinases, nitric oxide, interle ukin‑6, and prostaglandin E2. Spine 1996; 21(3): 271– 217.

41. Takahashi H. A mechanism for sci atic pain ca used by lumbar disc herni ati on- involvement of inflammatory cytokines with sci atic pain. Nippon Seikeigeka Gakkai Zasshi 1995; 69(1): 17– 29.

42. O’Donnell JL, O’Donnell AL. Prostaglandin E2 content in herni ated lumbar disc dise ase. Spine 1996; 21(14): 1653– 1655.

43. Cho i Y, Raja SN, Mo ore LC, Tobin JR. Ne uropathic pain in rats is associ ated with altered nitric oxide synthase activity in ne ural tissue. J Ne urol Sci 1996; 138(1– 2): 14– 20.

44. Kawaguchi S, Yamashita T, Katahira G, Yokozawa H, Torigoe T, Sato N. Chemokine profile of herni ated intervertebral discs infiltrated with monocytes and macrophages. Spine 2002; 27(14): 1511– 1516.

45. Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Spontaneo us producti on of monocyte chemo attractant protein‑1 and interle ukin‑8 by the human lumbar intervertebral disc. Spine 2002; 27(13): 1402– 1407.

46. Ikeda T, Nakamura T, Kikuchi T, Umeda S, Senda H, Takagi K. Pathomechanism of spontaneo us regressi on of the herni ated lumbar disc: histologic and immunohistochemical study. J Spinal Disord 1996; 9(2): 136– 140.

47. Hart PH, Vitti GF, Burgess DR, Whitty GA, Piccoli DS, Hamilton JA. Potenti al antiinflammatory effects of interle ukin 4: suppressi on of human monocyte tumor necrosis factor alpha, interle ukin 1, and prostaglandin E2. Proc Natl Acad Sci U S A 1989; 86(10): 3803– 3807.

48. Cunha FQ, Moncada S, Li ew FY. Interle ukin‑10 (IL‑10) inhibits the inducti on of nitric oxide synthase by interferon- gamma in murine macrophages. Bi ochem Bi ophys Res Commun 1992; 182(3): 1155– 1159.

49. Cunha FQ, Po ole S, Lorenzetti BB, Veiga FH, Ferreira SH. Cytokine- medi ated inflammatory hyperalgesi a limited by interle ukin‑4. Br J Pharmacol 1999; 126(1): 45– 50.

50. Rand N, Reichert F, Floman Y, Rotshenker S. Murine nucle us pulposus- derived cells secrete interle ukins- 1- beta, - 6, and -10 and granulocyte- macrophage colony- stimulating factor in cell culture. Spine 1997; 22(22): 2598– 2601.

51. Milligan ED, Slo ane EM, Langer SJ, Hughes TS, Jekich BM, Frank MG et al. Repe ated intrathecal injecti ons of plasmid DNA encoding interle ukin‑10 produce prolonged reversal of ne uropathic pain. Pain 2006; 126(1– 3): 294– 308.