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Synergetic Analgesia of Propentofylline and Electroacupuncture by Interrupting Spinal Glial Function in Rats

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Abstract

Previous studies indicated that disruption of glial function in the spinal cord enhanced electroacupuncture (EA) analgesia in arthritic rats, suggesting glia is involved in processing EA analgesia. To probe into the potential value for clinical practice, the present study was to investigate the effect of propentofylline, a glia inhibitor, on EA analgesia in rats. Mechanical allodynia induced by tetanic stimulation of sciatic nerve (TSS) was used as a pain model. On day 7 after TSS, EA treatment induced a significant increase in paw withdrawal threshold to mechanical stimulation. Intrathecal or intraperitoneal injection of propentofylline relieved TSS-induced mechanical allodynia. The combination of low dosage of propentofylline and EA produced more potent anti-allodynia than propentofylline or EA alone. Immunohistochemistry exhibited that TSS-induced activation of microglia and astrocytes was inhibited significantly by propentofylline. These results indicate that propentofylline and EA induce synergetic analgesia by interrupting spinal glial function.

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References

  1. Guasti L, Richardson D, Jhaveri M, Eldeeb K, Barrett D, Elphick MR, Alexander SPH, Kendall D, Michael GJ, Chapman V (2009) Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol Pain 5:35

    Article  PubMed  Google Scholar 

  2. Ziegler D (2008) Treatment of diabetic neuropathy and neuropathic pain how far have we come? Diabetes Care 31:S255–S261

    Article  CAS  PubMed  Google Scholar 

  3. Ying B, Lu N, Zhang YQ, Zhao ZQ (2006) Involvement of spinal glia in tetanically sciatic stimulation-induced bilateral mechanical allodynia in rats. Biochem Biophys Res Commun 340:1264–1272

    Article  CAS  PubMed  Google Scholar 

  4. Zhao ZQ (2008) Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 85:355–375

    Article  PubMed  Google Scholar 

  5. Hwang BG, Min BI, Kim JH, Na HS, Park DS (2002) Effects of electroacupuncture on the mechanical allodynia in the rat model of neuropathic pain. Neurosci Lett 320:49–52

    Article  CAS  PubMed  Google Scholar 

  6. Dai Y, Kondo E, Fukuoka T, Tokunaga A, Miki K, Noguchi K (2001) The effect of electroacupuncture on pain behaviors and noxious stimulus-evoked Fos expression in a rat model of neuropathic pain. J Pain 2:151–159

    Article  CAS  PubMed  Google Scholar 

  7. Kim HN, Park JH, Kim SK, Sun B, Koo S, Choi SM, Bae H, Min BI (2008) Electroacupuncture potentiates the antiallodynic effect of intrathecal neostigmine in a rat model of neuropathic pain. J Physiol Sci 58:357–360

    Article  PubMed  Google Scholar 

  8. Kim SK, Park JH, Bae SJ, Kim JH, Hwang BG, Min BI, Park DS, Na HS (2005) Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors. Exp Neurol 195:430–436

    Article  CAS  PubMed  Google Scholar 

  9. Watkins LR, Milligan ED, Maier SF (2001) Spinal cord glia: new players in pain. Pain 93:201–205

    Article  CAS  PubMed  Google Scholar 

  10. Cao H, Zhang YQ (2008) Spinal glial activation contributes to pathological pain states. Neurosci Biobehav Rev 32:972–983

    Article  PubMed  Google Scholar 

  11. Sun S, Cao H, Han M, Li TT, Pan HL, Zhao ZQ, Zhang YQ (2007) New evidence for the involvement of spinal fractalkine receptor in pain facilitation and spinal glial activation in rat model of monoarthritis. Pain 129:64–75

    Article  CAS  PubMed  Google Scholar 

  12. DeLeo JA, Yezierski RP (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90:1–6

    Article  CAS  PubMed  Google Scholar 

  13. Zhang RX, Liu B, Wang L, Ren K, Qiao JT, Berman BM, Lao L (2005) Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia. Pain 118:125–136

    Article  CAS  PubMed  Google Scholar 

  14. Sweitzer SM, Schubert P, DeLeo JA (2001) Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. J Pharmacol Exp Ther 297:1210–1217

    CAS  PubMed  Google Scholar 

  15. Ledeboer A, Sloane EM, Milligan ED, Frank MG, Mahony JH, Maier SF, Watkins LR (2005) Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115:71–83

    Article  CAS  PubMed  Google Scholar 

  16. Sun S, Cao H, Han M, Li TT, Zhao ZQ, Zhang YQ (2008) Evidence for suppression of electroacupuncture on spinal glial activation and behavioral hypersensitivity in a rat model of monoarthritis. Brain Res Bull 75:83–93

    Article  CAS  PubMed  Google Scholar 

  17. Sun S, Chen WL, Wang PF, Zhao ZQ, Zhang YQ (2006) Disruption of glial function enhances electroacupuncture analgesia in arthritic rats. Exp Neurol 198:294–302

    Article  PubMed  Google Scholar 

  18. Bachynsky J, McCracken P, Lier D, Alloul K, Jacobs P (2000) Propentofylline treatment for Alzheimer disease and vascular dementia: an economic evaluation based on functional abilities. Alzheimer Dis Assoc Disord 14:102–111

    Article  CAS  PubMed  Google Scholar 

  19. Kittner B (1999) Clinical trials of propentofylline in vascular dementia. European/Canadian propentofylline study group. Alzheimer Dis Assoc Disord 13(Suppl 3):S166–S171

    CAS  PubMed  Google Scholar 

  20. Zhang XC, Zhang YQ, Zhao ZQ (2005) Involvement of nitric oxide in long-term potentiation of spinal nociceptive responses in rats. Neuroreport 16:1197–1201

    Article  CAS  PubMed  Google Scholar 

  21. Liang LL, Wang ZY, Ning L, Yang JL, Zhang YQ, Zhao ZQ (2010) Involvement of nerve injury and activation of peripheral glial cells in tetanic sciatic stimulation-induced persistent pain in rats. J Neurosci Res. doi:10.1002/jnr.22439

  22. Wang ZY, Zhang YQ, Zhao ZQ (2006) Inhibition of tetanically sciatic stimulation-induced LTP of spinal neurons and Fos expression by disrupting glutamate transporter GLT-1. Neuropharmacology 51:764–772

    Article  CAS  PubMed  Google Scholar 

  23. Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450–455

    Article  CAS  PubMed  Google Scholar 

  24. Xu ZF, Wu GC, Cao XD (2002) Effect of electroacupuncture on the expression of interlukin-1beta mRNA after transient focal cerebral ischemia. Acupunct Electrother Res 27:29–35

    PubMed  Google Scholar 

  25. Ruzicka BB, Thompson RC, Watson SJ, Akil H (1996) Interleukin-1 beta-mediated regulation of mu-opioid receptor mRNA in primary astrocyte-enriched cultures. J Neurochem 66:425–428

    Article  CAS  PubMed  Google Scholar 

  26. Ruzicka BB, Akil H (1997) The interleukin-1beta-mediated regulation of proenkephalin and opioid receptor messenger RNA in primary astrocyte-enriched cultures. Neuroscience 79:517–524

    Article  CAS  PubMed  Google Scholar 

  27. Parkinson FE, Paterson AR, Young JD, Cass CE (1993) Inhibitory effects of propentofylline on [3H]adenosine influx. A study of three nucleoside transport systems. Biochem Pharmacol 46:891–896

    Article  CAS  PubMed  Google Scholar 

  28. Loram LC, Harrison JA, Sloane EM, Hutchinson MR, Sholar P, Taylor FR, Berkelhammer D, Coats BD, Poole S, Milligan ED, Maier SF, Rieger J, Watkins LR (2009) Enduring reversal of neuropathic pain by a single intrathecal injection of adenosine 2A receptor agonists: a novel therapy for neuropathic pain. J Neurosci 29:14015–14025

    Article  CAS  PubMed  Google Scholar 

  29. Sweitzer SM, Schubert P, DeLeo JA (2001) Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. J Pharmacol Exp Ther 297:1210–1217

    CAS  PubMed  Google Scholar 

  30. Liu C, Zhao F, Li W, Zhu L (1994) Role of adenosine in weak electro-acupuncture-induced depression of nociceptive response of spinal dorsal horn neurons in rats. Zhen Ci Yan Jiu 19:52–55

    PubMed  Google Scholar 

  31. Lavand’homme PM, Eisenach JC (1999) Exogenous and endogenous adenosine enhance the spinal antiallodynic effects of morphine in a rat model of neuropathic pain. Pain 80:31–36

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from National Basic Research Program of China (No. 2007CB512502 and 2007CB512303) and grants from National Nature Science Found of China (No. 30600178 and 30830044).

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Correspondence to Zhi-Qi Zhao.

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Ling-Li Liang, Jia-Le Yang contributed equally.

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Liang, LL., Yang, JL., Lü, N. et al. Synergetic Analgesia of Propentofylline and Electroacupuncture by Interrupting Spinal Glial Function in Rats. Neurochem Res 35, 1780–1786 (2010). https://doi.org/10.1007/s11064-010-0244-x

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