期刊论文详细信息
Molecular Pain
Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization
Jun Sato3  Takashi Nakano1  Hiroki Sakurai2  Yuqiang Li4  Atsuko Morimoto5  Takahiko Yoshimoto5  Hitoshi Ohishi1  Yusuke Ohmichi4  Mika Ohmichi5 
[1] Department of Anatomy, Aichi Medical University, Aichi 480-1195, Japan;Faculty of Health and Medical Sciences, Tokoha University, Hamamatsu 431-2102, Japan;Center for Animal Research and Education, Nagoya University, Aichi 464-8601, Japan;Multidisciplinary Pain Center, Aichi Medical University, Aichi 480-1195, Japan;Research Institute of Environmental Medicine, Nagoya University, Aichi 464-8601, Japan
关键词: Astrocytes;    Microglia;    Complex regional pain syndrome (CRPS) Type I;    Widespread hyperalgesia;    Chronic post-cast pain;    Cast immobilization;   
Others  :  861915
DOI  :  10.1186/1744-8069-10-6
 received in 2013-09-04, accepted in 2014-01-13,  发布年份 2014
PDF
【 摘 要 】

Background

In the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal.

Results

In the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-α-aminoadipate (L-α-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail.

Conclusions

These findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP.

【 授权许可】

   
2014 Ohmichi et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140725005404363.pdf 2044KB PDF download
122KB Image download
106KB Image download
110KB Image download
212KB Image download
61KB Image download
109KB Image download
61KB Image download
【 图 表 】

【 参考文献 】
  • [1]Yasuda T, Miki S, Yoshinaga N, Senba E: Effects of amitriptyline and gabapentin on bilateral hyperalgesia observed in an animal model of unilateral axotomy. Pain 2005, 115:161-170.
  • [2]Kim SH, Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50:355-363.
  • [3]Seltzer Z, Dubner R, Shir Y: A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990, 43:205-218.
  • [4]Merskey H, Bogduk N: Classification of Chronic Pain. 2nd edition. Seattle, WA: IASP Press; 1994.
  • [5]Maleki J, LeBel AA, Bennett GJ, Schwartzman RJ: Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy). Pain 2000, 88:259-266.
  • [6]Rommel O, Gehling M, Dertwinkel R, Witscher K, Zenz M, Malin JP, Janig W: Hemisensory impairment in patients with complex regional pain syndrome. Pain 1999, 80:95-101.
  • [7]Rommel O, Malin JP, Zenz M, Janig W: Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits. Pain 2001, 93:279-293.
  • [8]Jänig W, Baron R: Complex regional pain syndrome: mystery explained? Lancet Neurol 2003, 2:687-697.
  • [9]Allen G, Galer BS, Schwartz L: Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain 1999, 80:539-544.
  • [10]Galer BS, Henderson J, Perander J, Jensen MP: Course of symptoms and quality of life measurement in complex regional pain syndrome: a pilot survey. J Pain Symptom Manage 2000, 20:286-292.
  • [11]Schwartzman RJ, Kerrigan J: The movement disorder of reflex sympathetic dystrophy. Neurology 1990, 40:57-61.
  • [12]Bennett GJ, Xie YK: A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33:87-107.
  • [13]Decosterd I, Woolf CJ: Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 2000, 87:149-158.
  • [14]Coderre TJ, Xanthos DN, Francis L, Bennett GJ: Chronic post-ischemia pain (CPIP): a novel animal model of complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) produced by prolonged hindpaw ischemia and reperfusion in the rat. Pain 2004, 112:94-105.
  • [15]Sluka KA, Kalra A, Moore SA: Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve 2001, 24:37-46.
  • [16]Sluka KA, Radhakrishnan R, Benson CJ, Eshcol JO, Price MP, Babinski K, Audette KM, Yeomans DC, Wilson SP: ASIC3 in muscle mediates mechanical, but not heat, hyperalgesia associated with muscle inflammation. Pain 2007, 129:102-112.
  • [17]Guo TZ, Offley SC, Boyd EA, Jacobs CR, Kingery WS: Substance P signaling contributes to the vascular and nociceptive abnormalities observed in a tibial fracture rat model of complex regional pain syndrome type I. Pain 2004, 108:95-107.
  • [18]Ohmichi Y, Sato J, Ohmichi M, Sakurai H, Yoshimoto T, Morimoto A, Hashimoto T, Eguchi K, Nishihara M, Arai YC, Ohishi H, Asamoto K, Ushida T, Nakano T, Kumazawa T: Two-week cast immobilization induced chronic widespread hyperalgesia in rats. Eur J Pain 2012, 16:338-348.
  • [19]Morimoto A, Winaga H, Sakurai H, Ohmichi M, Yoshimoto T, Ohmichi Y, Matsui T, Ushida T, Okada T, Sato J: Treadmill running and static stretching improve long-lasting hyperalgesia, joint limitation, and muscle atrophy induced by cast immobilization in rats. Neurosci Lett 2013, 534:295-300.
  • [20]Tsuda M, Kohro Y, Yano T, Tsujikawa T, Kitano J, Tozaki-Saitoh H, Koyanagi S, Ohdo S, Ji RR, Salter MW, Inoue K: JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain 2011, 134:1127-1139.
  • [21]Inoue K, Tsuda M: Microglia and neuropathic pain. Glia 2009, 57:1469-1479.
  • [22]Zhuang ZY, Wen YR, Zhang DR, Borsello T, Bonny C, Strichartz GR, Decosterd I, Ji RR: A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance. J Neurosci 2006, 26:3551-3560.
  • [23]Kawasaki Y, Xu ZZ, Wang X, Park JY, Zhuang ZY, Tan PH, Gao YJ, Roy K, Corfas G, Lo EH, Ji RR: Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med 2008, 14:331-336.
  • [24]Milligan ED, Twining C, Chacur M, Biedenkapp J, O’Connor K, Poole S, Tracey K, Martin D, Maier SF, Watkins LR: Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. J Neurosci 2003, 23:1026-1040.
  • [25]Zhang J, De Koninck Y: Spatial and temporal relationship between monocyte chemoattractant protein-1 expression and spinal glial activation following peripheral nerve injury. J Neurochem 2006, 97:772-783.
  • [26]Beggs S, Trang T, Salter MW: P2X4R + microglia drive neuropathic pain. Nat Neurosci 2012, 15:1068-1073.
  • [27]Masuda T, Tsuda M, Yoshinaga R, Tozaki-Saitoh H, Ozato K, Tamura T, Inoue K: IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep 2012, 1:334-340.
  • [28]Gao YJ, Xu ZZ, Liu YC, Wen YR, Decosterd I, Ji RR: The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition. Pain 2010, 148:309-319.
  • [29]Chacur M, Milligan ED, Gazda LS, Armstrong C, Wang H, Tracey KJ, Maier SF, Watkins LR: A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats. Pain 2001, 94:231-244.
  • [30]Gao YJ, Ji RR: Light touch induces ERK activation in superficial dorsal horn neurons after inflammation: involvement of spinal astrocytes and JNK signaling in touch-evoked central sensitization and mechanical allodynia. J Neurochem 2010, 115:505-514.
  • [31]Huck S, Grass F, Hörtnagl H: The glutamate analogue alpha-aminoadipic acid is taken up by astrocytes before exerting its gliotoxic effect in vitro. J Neurosci 1984, 4:2650-2657.
  • [32]Ikeda H, Kiritoshi T, Murase K: Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat. Mol Pain 2012, 8:43. BioMed Central Full Text
  • [33]Birklein F, Kunzel W, Sieweke N: Despite clinical similarities there are significant differences between acute limb trauma and complex regional pain syndrome I (CRPS I). Pain 2001, 93:165-171.
  • [34]Sieweke N, Birklein F, Riedl B, Neundorfer B, Handwerker HO: Patterns of hyperalgesia in complex regional pain syndrome. Pain 1999, 80:171-177.
  • [35]Zhuang ZY, Gerner P, Woolf CJ, Ji RR: ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 2005, 114:149-159.
  • [36]Tsuda M, Shigemoto-Mogami Y, Koizumi S, Mizokoshi A, Kohsaka S, Salter MW, Inoue K: P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003, 424:778-783.
  • [37]Tsuda M, Mizokoshi A, Shigemoto-Mogami Y, Koizumi S, Inoue K: Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia 2004, 45:89-95.
  • [38]Sweitzer SM, Colburn RW, Rutkowski M, DeLeo JA: Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat. Brain Res 1999, 829:209-221.
  • [39]Calvo M, Bennett DL: The mechanisms of microgliosis and pain following peripheral nerve injury. Exp Neurol 2012, 234:271-282.
  • [40]Echeverry S, Shi XQ, Zhang J: Characterization of cell proliferation in rat spinal cord following peripheral nerve injury and the relationship with neuropathic pain. Pain 2008, 135:37-47.
  • [41]Liu L, Rudin M, Kozlova EN: Glial cell proliferation in the spinal cord after dorsal rhizotomy or sciatic nerve transection in the adult rat. Exp Brain Res 2000, 131:64-73.
  • [42]Murray M, Wang SD, Goldberger ME, Levitt P: Modification of astrocytes in the spinal cord following dorsal root or peripheral nerve lesions. Exp Neurol 1990, 110:248-257.
  • [43]Garrison CJ, Dougherty PM, Kajander KC, Carlton SM: Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res 1991, 565:1-7.
  • [44]Chen JJ, Lue JH, Lin LH, Huang CT, Chiang RP, Chen CL, Tsai YJ: Effects of pre-emptive drug treatment on astrocyte activation in the cuneate nucleus following rat median nerve injury. Pain 2010, 148:158-166.
  • [45]Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y: LTRPC2 Ca2 + -permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 2002, 9:163-173.
  • [46]Haraguchi K, Kawamoto A, Isami K, Maeda S, Kusano A, Asakura K, Shirakawa H, Mori Y, Nakagawa T, Kaneko S: TRPM2 contributes to inflammatory and neuropathic pain through the aggravation of pronociceptive inflammatory responses in mice. J Neurosci 2012, 32:3931-3941.
  • [47]Tsuda M, Masuda T, Kitano J, Shimoyama H, Tozaki-Saitoh H, Inoue K: IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain. Proc Natl Acad Sci U S A 2009, 106:8032-8037.
  • [48]Hains BC, Waxman SG: Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J Neurosci 2006, 26:4308-4317.
  文献评价指标  
  下载次数:8次 浏览次数:2次