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Role of the RVM in Descending Pain Regulation Originating from the Cerebrospinal Fluid-Contacting Nucleus

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Abstract

Evidence has suggested that cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) is correlated with the development and recurrence of pain. A recent research showed that the CSF-contacting nucleus acts as a component of the descending 5-hydroxytryptamine (5-HT) system and plays a role in descending pain inhibition. However, limited studies are conducted to investigate the relationship between the CSF-contacting nucleus and pain. In present study, we explored the effect of CSF-contacting nucleus on nociceptive behaviors in both normal and neuropathic rats via targeted ablation of the CSF-contacting nucleus in the brainstem, using cholera toxin subunit B-saporin (CB-SAP), a cytotoxin coupled to cholera toxin subunit B. The CB-SAP-treated rats showed aggravated thermal hyperalgesia and mechanical allodynia. Also, results from immunohistochemical experiments showed that rostral ventromedial medulla (RVM) received fiber projection from the CSF-contacting nucleus, which disappeared after ablation of the CSF-contacting nucleus, and the CB-SAP treated rats showed downregulation of c-Fos expression in the RVM as compared with the rats receiving i.c.v. injection of phosphate buffer saline (PBS). A significant downregulation of 5-HT-labeled neurons and tryptophan hydroxylase 2 (TPH2) as the marker of 5-HT cells in the RVM, and 5-HT expression in spinal dorsal horn in both normal and chronic constriction injury (CCI) rats after i.c.v. injection of CB-SAP was observed. These results suggested that RVM may be involved in descending pain modulation originating from the CSF-contacting nucleus.

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References

  1. Vigh B, Manzano e Silva MJ, Frank CL (2004) The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain. Histol Histopathol 19(2):607–628

    CAS  PubMed  Google Scholar 

  2. Zhang LC, Zeng YM, Ting J (2003) The distributions and signaling directions of the cerebrospinal fluid contacting neurons in the parenchyma of a rat brain. Brain Res 989(1):1–8

    Article  CAS  PubMed  Google Scholar 

  3. Zhou F, Wang J, Zhang H (2013) Evaluation of three tracers for labeling distal cerebrospinal fluid-contacting neurons. Neurosci Bull 29(5):576–580

    Article  CAS  PubMed  Google Scholar 

  4. Liu H, Yan WW, Lu XX (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475–485

    Article  CAS  PubMed  Google Scholar 

  5. Wu YH, Song SY, Liu H (2015) Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress. Neuropeptides 51:43–54

    Article  CAS  PubMed  Google Scholar 

  6. Xing D, Wu Y, Li G (2015) Role of cerebrospinal fluid-contacting nucleus in sodium sensing and sodium appetite. Physiol Behav 147:291–299

    Article  CAS  PubMed  Google Scholar 

  7. Li G, Lu X, Zhang S (2015) mTOR and Erk1/2 signaling in the cerebrospinal fluid-contacting nucleus is involved in neuropathic pain. Neurochem Res 40(5):1053–1062

    Article  CAS  PubMed  Google Scholar 

  8. Wang J, Zhang S, Li L (2015) Involvement of Wnt5a within the cerebrospinal fluid-contacting nucleus in nerve injury-induced neuropathic pain. Int J Neurosci 125(2):147–153

    Article  CAS  PubMed  Google Scholar 

  9. Wang XY, Yan WW, Zhang XL (2014) ASIC3 in the cerebrospinal fluid-contacting nucleus of brain parenchyma contributes to inflammatory pain in rats. Neurol Res 36(3):270–275

    Article  CAS  PubMed  Google Scholar 

  10. Chao CL, Lu XF, Zhang LC (2010) Formalin-induced pain stimulation induced expression of GABA in the distal cerebrospinal fluid contacting neurons. Zhongguo Ying Yong Sheng Li Xue Za Zhi 26(1):36–38

    CAS  PubMed  Google Scholar 

  11. Du J, Yang X, Zhang L (2009) Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats. Cerebrospinal Fluid Res 6:3

    Article  PubMed  PubMed Central  Google Scholar 

  12. Geng XJ, Lu XF, Zhang LC (2008) Expression of drebrin in the distal cerebrospinal fluid contacting neurons of rats with chronic constriction injury of sciatic nerve. Sheng Li Xue Bao 60(4):469–474

    CAS  PubMed  Google Scholar 

  13. Vanegas H, Schaible HG (2004) Descending control of persistent pain: Inhibitory or facilitatory? Brain Res Rev 46(3):295–309

    Article  PubMed  Google Scholar 

  14. Heinricher MM, Tavares I, Leith JL (2009) Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev 60(1):214–225

    Article  CAS  PubMed  Google Scholar 

  15. Li AH, Hwang HM, Tan PP (2001) Neurotensin excites periaqueductal gray neurons projecting to the rostral ventromedial medulla. J Neurophysiol 85(4):1479–1488

    CAS  PubMed  Google Scholar 

  16. Burgess SE, Gardell LR, Ossipov MH (2002) Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J Neurosci 22(12):5129–5136

    CAS  PubMed  Google Scholar 

  17. Mase H, Sakai A, Sakamoto A (2011) A subset of mu-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain. Neurosci Res 70(1):35–43

    Article  CAS  PubMed  Google Scholar 

  18. Bee LA, Dickenson AH (2007) Rostral ventromedial medulla control of spinal sensory processing in normal and pathophysiological states. Neuroscience 147(3):786–793

    Article  CAS  PubMed  Google Scholar 

  19. Zhuo M, Gebhart GF (1997) Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat. J Neurophysiol 78(2):746–758

    CAS  PubMed  Google Scholar 

  20. Millan MJ (2002) Descending control of pain. Prog Neurobiol 66(6):355–474

    Article  CAS  PubMed  Google Scholar 

  21. Bardin L (2011) The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol 22(5–6):390–404

    Article  CAS  PubMed  Google Scholar 

  22. Yoshimura M, Furue H (2006) Mechanisms for the anti-nociceptive actions of the descending noradrenergic and serotonergic systems in the spinal cord. J Pharmacol Sci 101(2):107–117

    Article  CAS  PubMed  Google Scholar 

  23. Budantsev A, Kisliuk OS, Shul’govskii VV (1993) The brain in stereotaxic coordinates (a textbook for colleges). Zh Vyssh Nerv Deiat Im I P Pavlova 43(5):1045–1051

    PubMed  Google Scholar 

  24. Bennett GJ, Xie YK (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33(1):87–107

    Article  CAS  PubMed  Google Scholar 

  25. Tortorici V, Morgan MM (2002) Comparison of morphine and kainic acid microinjections into identical PAG sites on the activity of RVM neurons. J Neurophysiol 88(4):1707–1715

    CAS  PubMed  Google Scholar 

  26. Ikeda H, Takasu S, Murase K (2014) Contribution of anterior cingulate cortex and descending pain inhibitory system to analgesic effect of lemon odor in mice. Mol Pain 10:14

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zhang YQ, Wu GC (2000) Endogenous descending inhibitory/facilitatory system and serotonin (5-HT) modulating spinal nociceptive transmission. Sheng Li Ke Xue Jin Zhan 31(3):211–216

    CAS  PubMed  Google Scholar 

  28. Ossipov MH, Morimura K, Porreca F (2014) Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care 8(2):143–151

    PubMed  PubMed Central  Google Scholar 

  29. Wei F, Dubner R, Ren K (1999) Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain 80(1–2):127–141

    Article  CAS  PubMed  Google Scholar 

  30. Zhao ZQ, Chiechio S, Sun YG (2007) Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs. J Neurosci 27(22):6045–6053

    Article  CAS  PubMed  Google Scholar 

  31. Kim YS, Chu Y, Han L (2014) Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain. Neuron 81(4):873–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wei F, Dubner R, Zou S (2010) Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain. J Neurosci 30(25):8624–8636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cai YQ, Wang W, Hou YY (2014) Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization. Mol Pain 10:70

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (NSFC81371243 to Prof. Zhang), the Natural Science Foundation of Jiangsu Province (BK2012580 to Prof. Zhang), and the Fund of Science and Technology Innovation Team in Jiangsu Province (2009) (to Prof. Zhang).

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    Authors and Affiliations

    1. Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou, 221004, Jiangsu Province, China

      Yan Fei, Xin Wang, Songsong Chen, Qiangqiang Zhou, Chao Zhang, Ying Li, Lihong Sun & Licai Zhang

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    1. Yan Fei
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    2. Xin Wang
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    3. Songsong Chen
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    8. Licai Zhang
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    Correspondence to Licai Zhang.

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    Yan Fei and Xin Wang have contributed equally to this work.

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    Fei, Y., Wang, X., Chen, S. et al. Role of the RVM in Descending Pain Regulation Originating from the Cerebrospinal Fluid-Contacting Nucleus. Neurochem Res 41, 1651–1661 (2016). https://doi.org/10.1007/s11064-016-1880-6

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    • DOI: https://doi.org/10.1007/s11064-016-1880-6

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