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Effects on Spatial Cognition and Nociceptive Behavior Following Peripheral Nerve Injury in Rats with Lesion of the Striatal Marginal Division Induced by Kainic Acid

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Abstract

Neuropathic pain and cognitive deficit are frequently comorbidity in clinical, but their underlying correlation and mechanisms remain unclear. Here, we utilized a combined rat model including kainic acid (KA) injection into bilateral striatal marginal division and chronic constriction nerve injury (CCI). PET/CT scans revealed that the SUVmax of KA rats was significantly decreased when compared to naive and saline rats. In contrast to the naive and saline rats, KA rats had longer latencies in locating the hidden platform on day 4, 5 in Morris water maze task. Thermal hyperalgesia and mechanical allodynia of KA rats were alleviated following CCI. Immunostaining results showed that substance P was markedly increased within ipsilateral spinal cord dorsal horn of KA rats after CCI, especially on the post-operative day 14. By means of real-time PCR, the up-regulation of GluR within ipsilateral spinal cord dorsal horn was observed in all KA and CCI rats. PKCγ, IL-6 and NF-κB were up-regulated in both CCI rats when compared to naive and their respective sham rats. These results suggest that cognitive impairment of rats altered the pain behaviors, and these intracellular regulators play crucial roles in the process of neuropathic pain.

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References

  1. Cook AK, Niven CA, Downs MG (1999) Assessing the pain of people with cognitive impairment. Int J Geriatr Psychiatry 14(6):421–425

    Article  CAS  PubMed  Google Scholar 

  2. Frampton M (2003) Experience assessment and management of pain in people with dementia. Age Ageing 32(3):248–251

    Article  PubMed  Google Scholar 

  3. Zwakhalen SM, Van’T HC, Hamers JP (2012) Systematic pain assessment using an observational scale in nursing home residents with dementia: exploring feasibility and applied interventions. J Clin Nurs 21(21–22):3009–3017

    Article  PubMed  Google Scholar 

  4. Eichenbaum H (2000) A cortical-hippocampal system for declarative memory. Nat Rev Neurosci 1(1):41–50

    Article  CAS  PubMed  Google Scholar 

  5. Engin E, Treit D (2007) The role of hippocampus in anxiety: intracerebral infusion studies. Behav Pharmacol 18(5–6):365–374

    Article  CAS  PubMed  Google Scholar 

  6. Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20(1):11–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shu SY, Wu YM, Bao XM, Leonard B (2003) Interactions among memory-related centers in the brain. J Neurosci Res 71(5):609–616

    Article  CAS  PubMed  Google Scholar 

  8. Shu SY (2003) Marginal division of the neostriatum: a subcortical memory center. J Biomed Sci 10(1):14–29

    Article  PubMed  Google Scholar 

  9. Shu SY, Bao XM, Zhang C, Li SX, Chan WY, Yew D (2000) A new subdivision, marginal division, in the neostriatum of the monkey brain. Neurochem Res 25(2):231–237

    Article  CAS  PubMed  Google Scholar 

  10. Zeng J, Shu SY, Bao X, Zou F, Ji A, Ye J (1999) Properties of acetylcholine receptor ion channels in the acutely dissociated neurons of the marginal division in the rat striatum. Neurochem Res 24(12):1571–1575

    Article  CAS  PubMed  Google Scholar 

  11. Shu SY, Wu YM, Bao XM, Wen ZB, Huang FH, Li SX, Fu QZ, Ning Q (2002) A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis. Mol Psychiatry 7(9):1018–1022

    Article  CAS  PubMed  Google Scholar 

  12. Chudler EH, Sugiyama K, Dong WK (1993) Nociceptive responses in the neostriatum and globus pallidus of the anesthetized rat. J Neurophysiol 69(6):1890–1903

    CAS  PubMed  Google Scholar 

  13. Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  14. Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ma Y, Zhan M, OuYang L, Li Y, Chen S, Wu J, Chen J, Luo C, Lei W (2014) The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats. Behav Brain Res 266:37–45

    Article  CAS  PubMed  Google Scholar 

  16. Feng Q, Ma Y, Mu S, Wu J, Chen S, Ouyang L, Lei W (2014) Specific reactions of different striatal neuron types in morphology induced by quinolinic acid in rats. PLoS One 9(3):e91512

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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 

  18. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32(1):77–88

    Article  CAS  PubMed  Google Scholar 

  19. Tal M, Bennett GJ (1994) Extra-territorial pain in rats with a peripheral mononeuropathy: mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve. Pain 57(3):375–382

    Article  CAS  PubMed  Google Scholar 

  20. Nadler JV, Cuthbertson GJ (1980) Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res 195(1):47–56

    Article  CAS  PubMed  Google Scholar 

  21. Bockstael O, Tenenbaum L, Dalkara D, Melas C, De Witte O, Levivier M, Chtarto A (2014) Intracisternal delivery of NFkappaB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment. Front Mol Neurosci 7:92

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nadler JV, Evenson DA, Cuthbertson GJ (1981) Comparative toxicity of kainic acid and other acidic amino acids toward rat hippocampal neurons. Neuroscience 6(12):2505–2517

    Article  CAS  PubMed  Google Scholar 

  23. Shaw PJ (1992) Excitatory amino acid neurotransmission, excitotoxicity and excitotoxins. Curr Opin Neurol Neurosurg 5(3):383–390

    CAS  PubMed  Google Scholar 

  24. Hynd MR, Scott HL, Dodd PR (2004) Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochem Int 45(5):583–595

    Article  CAS  PubMed  Google Scholar 

  25. Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V (2002) The tachykinin peptide family. Pharmacol Rev 54(2):285–322

    Article  CAS  PubMed  Google Scholar 

  26. Carvalho MC, Masson S, Brandao ML, de Souza SM (2008) Anxiolytic-like effects of substance P administration into the dorsal, but not ventral, hippocampus and its influence on serotonin. Peptides 29(7):1191–1200

    Article  CAS  PubMed  Google Scholar 

  27. Shu SY, Bao XM, Ning Q, Wu YM, Wang J, Leonard BE (2003) New component of the limbic system: marginal division of the neostriatum that links the limbic system to the basal nucleus of Meynert. J Neurosci Res 71(5):751–757

    Article  CAS  PubMed  Google Scholar 

  28. Wang S, Lim G, Zeng Q, Sung B, Ai Y, Guo G, Yang L, Mao J (2004) Expression of central glucocorticoid receptors after peripheral nerve injury contributes to neuropathic pain behaviors in rats. J Neurosci 24(39):8595–8605

    Article  CAS  PubMed  Google Scholar 

  29. 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(1–2):334–338

    Article  CAS  PubMed  Google Scholar 

  30. Wang S, Lim G, Zeng Q, Sung B, Yang L, Mao J (2005) Central glucocorticoid receptors modulate the expression and function of spinal NMDA receptors after peripheral nerve injury. J Neurosci 25(2):488–495

    Article  PubMed  Google Scholar 

  31. Oitzl MS, Fluttert M, Sutanto W, de Kloet ER (1998) Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats. Eur J Neurosci 10(12):3759–3766

    Article  CAS  PubMed  Google Scholar 

  32. Cameron SA, Dutia MB (1999) Lesion-induced plasticity in rat vestibular nucleus neurones dependent on glucocorticoid receptor activation. J Physiol 518(Pt 1):151–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Roozendaal B, McReynolds JR, McGaugh JL (2004) The basolateral amygdala interacts with the medial prefrontal cortex in regulating glucocorticoid effects on working memory impairment. J Neurosci 24(6):1385–1392

    Article  CAS  PubMed  Google Scholar 

  34. Gardell LR, Ibrahim M, Wang R, Wang Z, Ossipov MH, Malan TJ, Porreca F, Lai J (2004) Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain. Neuroscience 123(1):43–52

    Article  CAS  PubMed  Google Scholar 

  35. Mao J, Price DD, Phillips LL, Lu J, Mayer DJ (1995) Increases in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy. Neurosci Lett 198(2):75–78

    Article  CAS  PubMed  Google Scholar 

  36. Ohsawa M, Narita M, Mizoguchi H, Suzuki T, Tseng LF (2000) Involvement of spinal protein kinase C in thermal hyperalgesia evoked by partial sciatic nerve ligation, but not by inflammation in the mouse. Eur J Pharmacol 403(1–2):81–85

    Article  CAS  PubMed  Google Scholar 

  37. Sweitzer S, Martin D, DeLeo JA (2001) Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience 103(2):529–539

    Article  CAS  PubMed  Google Scholar 

  38. Opree A, Kress M (2000) Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci 20(16):6289–6293

    CAS  PubMed  Google Scholar 

  39. 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(3):1026–1040

    CAS  PubMed  Google Scholar 

  40. Chou CW, Wong GT, Lim G, Wang S, Irwin MG, Mao J (2011) Spatiotemporal pattern of concurrent spinal and supraspinal NF-kappaB expression after peripheral nerve injury. J Pain 12(1):13–21

    Article  CAS  PubMed  Google Scholar 

  41. Ma W, Bisby MA (1998) Increased activation of nuclear factor kappa B in rat lumbar dorsal root ganglion neurons following partial sciatic nerve injuries. Brain Res 797(2):243–254

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Natural Science Foundation of Guangdong Province (2014A030310455), Medical Scientific Research Foundation of Guangdong Province (B2014202), and National Science Foundations of China (31100806).

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    Authors and Affiliations

    1. Department of Anatomy, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China

      Yuxin Ma, Chang Zhou, Guoying Li, Jing Liu, Li Yan & Yuyun Jiang

    2. Department of Physiology, Southern Medical University, Guangzhou, People’s Republic of China

      Yinghong Tian

    3. Department of Physiology, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

      Sumin Tian

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    1. Yuxin Ma
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    Yuxin Ma and Chang Zhou contributed equally to this work.

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    Ma, Y., Zhou, C., Li, G. et al. Effects on Spatial Cognition and Nociceptive Behavior Following Peripheral Nerve Injury in Rats with Lesion of the Striatal Marginal Division Induced by Kainic Acid. Neurochem Res 40, 2357–2364 (2015). https://doi.org/10.1007/s11064-015-1727-6

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