Neurochemical Research

, Volume 31, Issue 3, pp 333–340 | Cite as

Glial Activation and Segmental Upregulation of Interleukin-1β (IL-1β) in the Rat Spinal Cord after Surgical Incision

  • Di Fu
  • Qulian Guo
  • Yuhang Ai
  • Hongwei Cai
  • Jianqin Yan
  • Ruping Dai


The present study investigated the expression patterns of glial cells and interleukin-1β (IL-1β) in the rat spinal cord after a surgical incision, which is closely related with clinical postoperative pain. Microglia and astrocytes became activated in the spinal cord following incision. Real-time polymerase chain reaction (PCR) and immunohistochemisty showed that IL-1β mRNA and protein level in the spinal cord was transiently upregulated after surgical incision. The increased IL-1β-immunoreactivity (IR) was mainly localized in neurons but not the activated microglia or astrocytes. Although obvious increase in IL-1β-IR could be observed in the lumbar segments of the spinal cord ipsilateral to a hind paw incision, significant upregulation of IL-1β was not detected in the lumbar segments following thoracic incision. The present study indicated that surgical incision could induce glial activation and segmental upregulation of IL-1β in the spinal cord. The activated glial cells and upregulated IL-1β, in turn, may be involved in the incision-induced pain hypersensitivity.


Cytokines Postoperative pain Spinal cord Interleukin-1β (IL-1β) 


  1. 1.
    Hunt SP, Mantyh PW (2001) The molecular dynamics of pain control. Nat Rev Neurosci 2:83–91CrossRefPubMedGoogle Scholar
  2. 2.
    Ji RR, Woolf CJ (2001) Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis 8:1–10CrossRefPubMedGoogle Scholar
  3. 3.
    Scholz J, Woolf CJ (2002) Can we conquer pain? Nat Neurosci 5(Suppl):1062–1067CrossRefPubMedGoogle Scholar
  4. 4.
    DeLeo JA, Yezierski RP (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90:1–6CrossRefPubMedGoogle Scholar
  5. 5.
    Watkins LR, Milligan ED, Maier SF (2001) Spinal cord glia: new players in pain. Pain 93:201–205CrossRefPubMedGoogle Scholar
  6. 6.
    Watkins LR, Maier SF (2002) Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 82:981–1011PubMedGoogle Scholar
  7. 7.
    Sweitzer SM, Colburn RW, Rutkowski M, DeLeo JA (1999) Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat. Brain Res 829:209–221CrossRefPubMedGoogle Scholar
  8. 8.
    Choi HS, Lee HJ, Jung CY, Ju JS, Park JS, Ahn DK (2003) Central cyclooxygenase-2 participates in interleukin-1 beta-induced hyperalgesia in the orofacial formalin test of freely moving rats. Neurosci Lett 352:187–190CrossRefPubMedGoogle Scholar
  9. 9.
    Falchi M, Ferrara F, Gharib C, Dib B (2001) Hyperalgesic effect of intrathecally administered interleukin-1 in rats. Drugs Exp Clin Res 27:97–101PubMedGoogle Scholar
  10. 10.
    Reeve AJ, Patel S, Fox A, Walker K, Urban L (2000) Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur J Pain 4:247–257CrossRefPubMedGoogle Scholar
  11. 11.
    Milligan ED, Twining C, Chacur M, Biedenkapp J, O’Connor K, Poole S, Tracey K, Martin D, Maier SF, Watkins LR (2003) Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci 23:1026–1040PubMedGoogle Scholar
  12. 12.
    Brennan TJ, Vandermeulen EP, Gebhart GF (1996) Characterization of a rat model of incisional pain. Pain 64:493–501CrossRefPubMedGoogle Scholar
  13. 13.
    Zahn PK, Brennan TJ (1998) Lack of effect of intrathecally administered N-methyl-d-aspartate receptor antagonists in a rat model for postoperative pain. Anesthesiology 88:143–156CrossRefPubMedGoogle Scholar
  14. 14.
    Zahn PK, Umali E, Brennan TJ (1998) Intrathecal non-NMDA excitatory amino acid receptor antagonists inhibit pain behaviors in a rat model of postoperative pain. Pain 74:213–223CrossRefPubMedGoogle Scholar
  15. 15.
    Ho ST, Wang JJ, Liaw WJ, Lee HK, Lee SC (1999) Surgical pain attenuates acute morphine tolerance in rats. Br J Anaesth 82:112–116PubMedGoogle Scholar
  16. 16.
    Budsberg SC, Cross AR, Quandt JE, Pablo LS, Runk AR (2002) Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs. Am J Vet Res 63:1557–1563CrossRefPubMedGoogle Scholar
  17. 17.
    Zimmermann M (1983) Ethical guidelines for investigation of experimental pain in conscious animals. Pain 16:109–110CrossRefPubMedGoogle Scholar
  18. 18.
    Zhu X, Conklin D, Eisenach JC (2003) Cyclooxygenase-1 in the spinal cord plays an important role in postoperative pain. Pain 104:15–23CrossRefPubMedGoogle Scholar
  19. 19.
    Fu D, Ng YK, Gan P, Ling EA (2004) Permanent occlusion of the middle cerebral artery upregulates expression of cytokines and neuronal nitric oxide synthase in the spinal cord and urinary bladder in the adult rat. Neuroscience 125:819–831CrossRefPubMedGoogle Scholar
  20. 20.
    Muller PY, Janovjak H, Miserez AR, Dobbie Z (2002) Processing of gene expression data generated by quantitative real-time RT-PCR. Biotechniques 32:1372–1379PubMedGoogle Scholar
  21. 21.
    Dai RP, Dheen ST, He BP, Tay SSW (2004) Differential Expression of Cytokines in the myocardium in response to sustained volume overload Eur J Heart Failure 6:693–703CrossRefGoogle Scholar
  22. 22.
    Dai RP, He BP, Dheen ST, Tay SSW (2004) Acute cardiac injury induces glial cell response and activates extracellular signaling-regulated kinase-1 and -2 in the spinal cord. Neurosci Lett .366:34–38CrossRefPubMedGoogle Scholar
  23. 23.
    Bursztajn S, Rutkowski MD, Deleo JA (2004) The role of the N-methyl-d-aspartate receptor NR1 subunit in peripheral nerve injury-induced mechanical allodynia, glial activation and chemokine expression in the mouse Neuroscience 125:269–275CrossRefPubMedGoogle Scholar
  24. 24.
    Zahn PK, Sluka KA, Brennan TJ (2002) Excitatory amino acid release in the spinal cord caused by plantar incision in the rat. Pain 100:65–76CrossRefPubMedGoogle Scholar
  25. 25.
    Bao L, Zhu Y, Elhassan AM, Wu Q, Xiao B, Zhu J, Lindgren JU (2001) Adjuvant-induced arthritis: IL-1 beta, IL-6 and TNF-alpha are up-regulated in the spinal cord. Neuroreport 12:3905–3908CrossRefPubMedGoogle Scholar
  26. 26.
    Pan JZ, Ni L, Sodhi A, Aguanno A, Young W, Hart RP (2002) Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. J Neurosci Res 68:315–322CrossRefPubMedGoogle Scholar
  27. 27.
    Boddeke EW (2001) Involvement of chemokines in pain. Eur J Pharmacol 429:115–119CrossRefPubMedGoogle Scholar
  28. 28.
    Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP (2002) Molecular mechanisms of cancer pain. Nat Rev Cancer 2:201–209CrossRefPubMedGoogle Scholar
  29. 29.
    Bledsoe AW, Jackson CA, McPherson S, Morrow CD (2000) Cytokine production in motor neurons by poliovirus replicon vector gene delivery. Nat Biotechnol 18:964–969CrossRefPubMedGoogle Scholar
  30. 30.
    Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV, Woolf CJ (2001) Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410:471–475PubMedCrossRefGoogle Scholar
  31. 31.
    Dolan S, Kelly JG, Huan M, Nolan AM (2003) Transient up-regulation of spinal cyclooxygenase-2 and neuronal nitric oxide synthase following surgical inflammation. Anesthesiogloy 98:170–180CrossRefGoogle Scholar
  32. 32.
    Kroin JS, Ling ZD, Buvanendran A, Tuman KJ (2004) Upregulation of spinal cyclooxygenase-2 in rats after surgical incision. Anesthesiology 100:364–369CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Di Fu
    • 1
  • Qulian Guo
    • 1
  • Yuhang Ai
    • 1
  • Hongwei Cai
    • 1
  • Jianqin Yan
    • 1
  • Ruping Dai
    • 1
    • 2
    • 3
  1. 1.Department of Anesthesiology, Xiang-Ya Hospital, Xiang-Ya College of MedicineCentral South UniversityChangshaChina
  2. 2.Gene Expression and Regulatory BiologyInstitute of Molecular and Cell BiologySingaporeSingapore
  3. 3.Department of Anesthesiology, Xiang-Ya Hospital, Xiang-Ya College of MedicineCentral South UniversityChangshaChina

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