Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

Molecular Pain

Jun Yi²  Shui-bing Liu³  Ming-gao Zhao³  Nan Zhang³  Jia-ze An²  Guang-bin Cui¹ 

[1] Department of Diagnostic Radiology, Tangdu Hospital, Xi'an 710032, China;Department of General Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China;Department of Pharmacology, Fourth Military Medical University, Xi'an 710032, China

关键词: Cingulate cortex;    Pain;    Inflammation;    Interleukin-8;   

Others  :  865526
DOI  :  10.1186/1744-8069-8-11

 received in 2011-11-30, accepted in 2012-02-12,  发布年份 2012

【 摘 要 】

Background

Interleukin-8 (IL-8) is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC), is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain.

Findings

In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC), and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA) in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA) revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice.

Conclusions

Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

【 授权许可】

   
2012 Cui et al; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Luster AD: Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 1998, 338:436-445.
• [2]Baggiolini M: Chemokines and leukocyte traffic. Nature 1998, 392:565-568.
• [3]Horuk R, Martin AW, Wang Z, Schweitzer L, Gerassimides A, Guo H, Lu Z, Hesselgesser J, Perez HD, Kim J, et al.: Expression of chemokine receptors by subsets of neurons in the central nervous system. J Immunol 1997, 158:2882-2890.
• [4]Ehrlich LC, Hu S, Sheng WS, Sutton RL, Rockswold GL, Peterson PK, Chao CC: Cytokine regulation of human microglial cell IL-8 production. J Immunol 1998, 160:1944-1948.
• [5]Puma C, Danik M, Quirion R, Ramon F, Williams S: The chemokine interleukin-8 acutely reduces Ca(2+) currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs. J Neurochem 2001, 78:960-971.
• [6]Casilli F, Bianchini A, Gloaguen I, Biordi L, Alesse E, Festuccia C, Cavalieri B, Strippoli R, Cervellera MN, Di Bitondo R, et al.: Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2. Biochem Pharmacol 2005, 69:385-394.
• [7]Zhuo M: Molecular mechanisms of pain in the anterior cingulate cortex. J Neurosci Res 2006, 84:927-933.
• [8]Zhao MG, Ko SW, Wu LJ, Toyoda H, Xu H, Quan J, Li J, Jia Y, Ren M, Xu ZC, Zhuo M: Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. J Neurosci 2006, 26:8923-8930.
• [9]Jia D, Gao GD, Liu Y, He SM, Zhang XN, Zhang YF, Zhao MG: TNF-alpha involves in altered prefrontal synaptic transmission in mice with persistent inflammatory pain. Neurosci Lett 2007, 415:1-5.
• [10]Toyoda H, Zhao MG, Zhuo M: Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain. Mol Pain 2009, 5:4. BioMed Central Full Text
• [11]Rostene W, Dansereau MA, Godefroy D, Van Steenwinckel J, Reaux-Le Goazigo A, Melik-Parsadaniantz S, Apartis E, Hunot S, Beaudet N, Sarret P: Neurochemokines: a menage a trois providing new insights on the functions of chemokines in the central nervous system. J Neurochem 2011, 118:680-694.
• [12]Penna G, Mondaini N, Amuchastegui S, Degli Innocenti S, Carini M, Giubilei G, Fibbi B, Colli E, Maggi M, Adorini L: Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia. Eur Urol 2007, 51:524-533. discussion 533
• [13]Kim SJ, Park SM, Cho YW, Jung YJ, Lee DG, Jang SH, Park HW, Hwang SJ, Ahn SH: Changes in expression of mRNA for interleukin-8 and effects of IL-8 receptor inhibitor in the spinal dorsal horn in a rat model of lumbar disc herniation. Spine (Phila Pa 1976) 2011.
• [14]Kushi H, Saito T, Makino K, Hayashi N: IL-8 is a key mediator of neuroinflammation in severe traumatic brain injuries. Acta Neurochir Suppl 2003, 86:347-350.
• [15]Otto VI, Heinzel-Pleines UE, Gloor SM, Trentz O, Kossmann T, Morganti-Kossmann MC: sICAM-1 and TNF-alpha induce MIP-2 with distinct kinetics in astrocytes and brain microvascular endothelial cells. J Neurosci Res 2000, 60:733-742.
• [16]Creager R, Dunwiddie T, Lynch G: Paired-pulse and frequency facilitation in the CA1 region of the in vitro rat hippocampus. J Physiol 1980, 299:409-424.
• [17]Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko SW, Jia YH, Shum FW, Zerbinatti CV, Bu G, et al.: Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. J Neurosci 2005, 25:11107-11116.
• [18]Raghavendra V, Tanga FY, DeLeo JA: Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci 2004, 20:467-473.
• [19]Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC: Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 1997, 277:968-971.
• [20]Zhuo M, Wu G, Wu LJ: Neuronal and microglial mechanisms of neuropathic pain. Mol Brain 2011, 4:31. BioMed Central Full Text
• [21]Wu LJ, Zhuo M: Resting microglial motility is independent of synaptic plasticity in mammalian brain. J Neurophysiol 2008, 99:2026-2032.
• [22]Zhuo M: Cortical plasticity as a new endpoint measurement for chronic pain. Mol Pain 2011, 7:54. BioMed Central Full Text
• [23]D'Mello R, Dickenson AH: Spinal cord mechanisms of pain. Br J Anaesth 2008, 101:8-16.
• [24]Woolf CJ: Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011, 152:S2-15.
• [25]Ren K, Dubner R: Enhanced descending modulation of nociception in rats with persistent hindpaw inflammation. J Neurophysiol 1996, 76:3025-3037.
• [26]Hargreaves K, Dubner R, Brown F, Flores C, Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988, 32:77-88.
• [27]Hu J, Wang Z, Guo YY, Zhang XN, Xu ZH, Liu SB, Guo HJ, Yang Q, Zhang FX, Sun XL, Zhao MG: A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain. Mol Pain 2009, 5:71. BioMed Central Full Text
• [28]Cheppudira BP: Characterization of hind paw licking and lifting to noxious radiant heat in the rat with and without chronic inflammation. J Neurosci Methods 2006, 155:122-125.
• [29]Zhao MG, Toyoda H, Lee YS, Wu LJ, Ko SW, Zhang XH, Jia Y, Shum F, Xu H, Li BM, et al.: Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron 2005, 47:859-872.
• [30]Chen L, Liu JC, Zhang XN, Guo YY, Xu ZH, Cao W, Sun XL, Sun WJ, Zhao MG: Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain. Neuropharmacology 2008, 54:1175-1181.