Top

European Spine Journal

Published in:

01-11-2011 | Original Article

The effect of repeated restraint stress in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats

Authors: Kazuhide Uesugi, Miho Sekiguchi, Shin-ichi Kikuchi, Shin-ichi Konno

Published in: European Spine Journal | Issue 11/2011

Abstract

Introduction

Chronic pain has an impact on psychological and social factors. It is known that stress influences physiological and behavioral changes and affects several neurotransmitter and hormonal systems. It is also known that corticosterone is increased by stress. The role of chronic stress in sciatica in lumbar disc herniation (LDH) in rats has not been investigated. The aim of this study was to investigate the effect of the restraint stress (RS) on pain-related behavior induced by application of nucleus pulposus (NP) in rats.

Materials and methods

Adult female Sprague–Dawley rats were divided into six experimental groups (naive group; naive + RS; sham group; sham + RS; autologous nucleus pulposus [NP] applied on the left L5 nerve root [NP group]; and NP + RS group). Von Frey tests were used to test pain-related behavior. Concentrations of plasma corticosterone were measured to assess changes in levels of endogenous corticosterone caused by RS. Expression of ATF-3 in the left L5 DRG was examined by immunohistochemical analyses in each group.

Results

Mechanical withdrawal thresholds of the NP and NP + RS groups were significantly decreased after surgery compared with the naive group. Although the thresholds in the NP group recovered after 28 days, the thresholds in the NP + RS group were significantly decreased during the 42 days after surgery. RS increased the concentration of plasma corticosterone at 21 and 42 days after surgery. In the NP and the NP + RS groups, the expression of ATF-3 was significantly increased at 7 days after surgery. The expression of ATF-3 was sustained for 21 days by RS.

Conclusion

Concentrations of plasma corticosterone were increased in three groups that underwent RS. The pain-related behavior persisted for the long term in the LDH model. The expression of ATF-3 in DRG neurons increased for 21 days by RS. These results suggest that RS plays a role in the chronicity of pain-related behavior in the LDH rats.

Alexander JK, DeVries AC, Kigerl KA et al (2009) Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation. Brain Behav Immun 23:851–860PubMedCrossRef

Aoki Y, Rydevik B, Kikuchi S et al (2002) Local application of disc-related cytokines on spinal nerve roots. Spine 27:1614–1617PubMedCrossRef

Cintra A, Molander C, Fuxe K (1993) Colocalization of Fos- and glucocorticoid receptor-immunoreactivities is present only in a very restricted population of dorsal horn neurons of the rat spinal cord after nociceptive stimulation. Brain Res 632:334–338PubMedCrossRef

Crofford LJ, Engleberg NC, Demitrack MA (1996) Neurohormonal perturbations in fibromyalgia. Baillieres Clin Rheumatol 10:365–378PubMedCrossRef

da Silva Torres IL, Cucco SNS, Bassani M et al (2003) Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration. Neurosci Res (NY) 45:277–283CrossRef

DeLeo JA (2006) Basic science of pain. J Bone Joint Surg Am 88:58–62PubMedCrossRef

De Nicola AF, Moses DF, Gonzalez S et al (1989) Adrenocorticoid action in the spinal cord: some unique molecular properties of glucocorticoid receptors. Cell Mol Neurobiol 9:179–192PubMedCrossRef

Fuxe K, Diaz R, Cintra A et al (1996) On the role of glucocorticoid receptors in brain plasticity. Cell Mol Neurobiol 16:239–258PubMedCrossRef

Gallo PV, Weinberg J (1981) Corticosterone rhythmicity in the rat: interactive effects of dietary restriction and schedule of feeding. J Nutr 111:208–218PubMed

10.

Gamaro GD, Xavier MH, Denardin JD et al (1998) The effects of acute and repeated restraint stress on the nociceptive response in rats. Physiol Behav 63:693–697PubMedCrossRef

11.

Gold SM, Mohr DC, Huitinga I et al (2005) The role of stress-response systems for the pathogenesis and progression of MS. Trends Immunol 26:644–652PubMedCrossRef

12.

Greco CM, Rudy TE, Manzi S (2004) Effects of a stress-reduction program on psychological function, pain, and physical function of systemic lupus erythematosus patients: a randomized controlled trial. Arthritis Rheum 51:625–634PubMedCrossRef

13.

Hasenbring M, Marienfeld G, Kuhlendahl D et al (1994) Risk factors of chronicity in lumbar disc patients. A prospective investigation of biologic, psychologic, and social predictors of therapy outcome. Spine 19:2759–2765PubMedCrossRef

14.

Igarashi T, Kikuchi S, Shubayev V et al (2000) 2000 Volvo Award winner in basic science studies: exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine 25:2975–2980PubMedCrossRef

15.

Joels M, Krugers HJ (2007) LTP after stress: up or down? Neural Plast 2007:93202PubMedCrossRef

16.

Kato K, Kikuchi S, Konno S, Sekiguchi M (2008) Participation of 5-hydroxytryptamine in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats. Spine 3(12):1330–1336CrossRef

17.

Kawakami M, Tamaki T, Weinstein JN et al (1996) Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat. Spine 21:2101–2107PubMedCrossRef

18.

Kayama S, Konno S, Olmarker K et al (1996) Incision of the anulus fibrosus induces nerve root morphologic, vascular, and functional changes. An experimental study. Spine 21:2539–2543PubMedCrossRef

19.

Khasar SG, Burkham J, Dina OA et al (2008) Stress induces a switch of intracellular signaling in sensory neurons in a model of generalized pain. J Neurosci 28:5721–5730PubMedCrossRef

20.

Khasar SG, Dina OA, Green PG et al (2009) Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is maintained by sympathoadrenal catecholamines. J Pain 10:1073–1077PubMedCrossRef

21.

Khasar SG, Green PG, Levine JD (2005) Repeated sound stress enhances inflammatory pain in the rat. Pain 116:79–86PubMedCrossRef

22.

Kingery WS, Guo T, Agashe GS et al (2001) Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation. Brain Res 913:140–148PubMedCrossRef

23.

Kobayashi H, Kato K, Kikuchi S, Konno S, Sekiguchi M (2011) Interactions of 5-hydroxytryptamine and tumor necrosis factor-α to pain-related behavior by mucleus pulposus applied on the nerve root in rats. Spine 36(3):210–218PubMedCrossRef

24.

Lephart ED, Galindo E, Bu LH (2003) Stress (hypothalamic-pituitary-adrenal axis) and pain response in male rats exposed lifelong to high versus low phytoestrogen diets. Neurosci Lett 342:65–68PubMedCrossRef

25.

McCarron RF, Wimpee MW, Hudkins PG et al (1987) The inflammatory effect of nucleus pulposus. A possible element in the pathogenesis of low-back pain. Spine 12:760–764PubMedCrossRef

26.

McLaughlin KJ, Gomez JL, Baran SE et al (2007) The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Brain Res 1161:56–64PubMedCrossRef

27.

Miyoshi S, Sekiguchi M, Konno S, Kikuchi S, Kanaya F (2011) Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats. Spine 36(1):E1–E6PubMedCrossRef

28.

Moore RA, Evans PJ, Smith RF et al (1983) Increased cortisol excretion in chronic pain. Anaesthesia 38:788–791PubMedCrossRef

29.

Neeck G, Crofford LJ (2000) Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am 26:989–1002PubMedCrossRef

30.

Neeck G, Renkawitz R, Eggert M (2002) Molecular aspects of glucocorticoid hormone action in rheumatoid arthritis. Cytokines Cell Mol Ther 7:61–69PubMedCrossRef

31.

Nicholson K, Martelli MF (2004) The problem of pain. J Head Trauma Rehabil 19:2–9PubMedCrossRef

32.

Olmarker K, Brisby H, Yabuki S et al (1997) The effects of normal, frozen, and hyaluronidase-digested nucleus pulposus on nerve root structure and function. Spine 22:471–475PubMedCrossRef

33.

Olmarker K, Rydevik B, Nordborg C (1993) Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 18:1425–1432PubMed

34.

Olmarker K, Larsson K (1998) Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. Spine 23:2538–2544PubMedCrossRef

35.

Otani K, Arai I, Mao GP et al (1997) Experimental disc herniation: evaluation of the natural course. Spine 22:2894–2899PubMedCrossRef

36.

Otoshi K, Kikuchi S, Konno S, Sekiguchi M (2011) Anti-HIMGB1 nurtralization antibody improves pain-related behavior induced by application of anutologous nucleus pulposus onto nerve roots in rats. Spine [Epub ahead of print]

37.

Otoshi K, Kikuchi S, Konno S, Sekiguchi M (2010) The reactions of glial cells and endoneurial macrophages in the dorsal root. Ganglion and their contribution to pain-related behavior after application of nucleus pulposus onto the nerve root in rats. Spine 35(1):10–17PubMedCrossRef

38.

Rand N, Reichert F, Floman Y et al (1997) Murine nucleus pulposus-derived cells secrete interleukins-1-beta, -6, and -10 and granulocyte-macrophage colony-stimulating factor in cell culture. Spine 22:2598–2601PubMedCrossRef

39.

Sasaki N, Sekiguchi M, Kilichi S, Konno S (2011) Effects of asialo erhythropoietin on pain-related behavior and expression of phosphorylated p38 MAP kinase and tumor necrosis factor-alpha induced by application of aurologous nuxleus pulposus on nerve root in rat. Spine 36(2):E86–E94PubMedCrossRef

40.

Sekiguchi M, Otoshi K, Kikuchi S, and Konno S (2011) Analgesic effects of prostaglandin E2 receptor subtype EP1 receptor antagonis––experimental study of application of nucleus pulposus. Spine [Epub ahead of print]

41.

Strang P (1998) Cancer pain––a provoker of emotional, social and existential distress. Acta Oncol 37:641–644PubMedCrossRef

42.

Tachihara H, Sekiguchi M, Kikuchi S, Konno S (2008) Do corticosteroids produce additional benefit in nerve root infiltration for lumbar disc herniation? Spine 33(7):743–747PubMedCrossRef

43.

Takahashi Y, Nakajima Y (1996) Dermatomes in the rat limbs as determined by antidromic stimulation of sensory C-fibers in spinal nerves. Pain 67:197–202PubMedCrossRef

44.

Takayama B, Sekiguchi M, Yabuki S, Kikuchi S, Konno S (2011) Localization and function of insulin-like growth factor 1 in dorsal root ganglia in a rat disc herniation model. Spine 36(2):E75–E79PubMedCrossRef

45.

Takayama B, Sekiguchi M, yabuki S, Fujita I, Shimada H, Kikuchi S (2008) Gene expression changes in dorsal root ganglion of rat experimental lumber disc herniation models. Spine 33(17):1829–1835PubMedCrossRef

46.

Turner JA, Jensen MP, Warms CA et al (2002) Catastrophizing is associated with pain intensity, psychological distress, and pain-related disability among individuals with chronic pain after spinal cord injury. Pain 98:127–134PubMedCrossRef

47.

Vershinina EA (1999) Pain sensitivity in chronic psychoemotional stress in humans. Neurosci Behav Physiol 29:333–337PubMedCrossRef

48.

Wang S, Lim G, Zeng Q et al (2004) Expression of central glucocorticoid receptors after peripheral nerve injury contributes to neuropathic pain behaviors in rats. J Neurosci 24:8595–8605PubMedCrossRef

49.

Watanabe K, Konno S, Sekiguchi M, Sasaki N, Honda Y, Kikuchi S (2007) Increase of 200-kDa nuerofilament-immunoreactive afferents in the substantia gelatinosa in allodynia rats induced by compression of the dorsal root ganglion. Spine 32:1265–1271PubMedCrossRef

50.

Yan P, Xu J, Li Q et al (1999) Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats. J Neurosci 19:9355–9363PubMed

Title: The effect of repeated restraint stress in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats
Authors: Kazuhide Uesugi
Miho Sekiguchi
Shin-ichi Kikuchi
Shin-ichi Konno
Publication date: 01-11-2011
Publisher: Springer-Verlag
Published in: European Spine Journal / Issue 11/2011
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-011-1877-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The effect of repeated restraint stress in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats

Abstract

Introduction

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2011

Porcine model of early onset scoliosis based on animal growth created with posterior mini-invasive spinal offset tethering A preliminary report

Analysis of failure following anterior screw fixation of Type II odontoid fractures in geriatric patients

Etanercept attenuates pain-related behavior following compression of the dorsal root ganglion in the rat

The effects of dynamic loading on the intervertebral disc

Prospective study of the effect of pedicle screw placement on development of the immature vertebra in an in vivo porcine model

Langerhans cell histiocytosis with multiple spinal involvement