Direct evidence for spinal cord microglia in the development of a neuropathic pain-like state in mice

被引:118
作者
Narita, Minoru [1 ]
Yoshida, Takuya [1 ]
Nakajima, Mayumi [1 ]
Narita, Michiko [1 ]
Miyatake, Mayumi [1 ]
Takagi, Tomoe [1 ]
Yajima, Yoshinori [1 ]
Suzuki, Tsutomu [1 ]
机构
[1] Hoshi Univ, Dept Toxicol, Sch Pharm & Pharmaceut Sci, Shinagawa Ku, Tokyo 1428501, Japan
关键词
activation; microglia; neuropathic pain; proliferation; spinal cord;
D O I
10.1111/j.1471-4159.2006.03808.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The present study was undertaken to further investigate the role of glial cells in the development of the neuropathic pain-like state induced by sciatic nerve ligation in mice. At 7 days after sciatic nerve ligation, the immunoreactivities (IRs) of the specific astrocyte marker glial fibrillary acidic protein (GFAP) and the specific microglial marker OX-42, but not the specific oligodendrocyte marker O4, were increased on the ipsilateral side of the spinal cord dorsal horn in nerve-ligated mice compared with that on the contralateral side. Furthermore, a single intrathecal injection of activated spinal cord microglia, but not astrocytes, caused thermal hyperalgesia in naive mice. Furthermore, 5-bromo-2'-deoxyuridine (BrdU)-positive cells on the ipsilateral dorsal horn of the spinal cord were significantly increased at 7 days after nerve ligation and were highly co-localized with another microglia marker, ionized calcium-binding adaptor molecule 1 (Iba1), but neither with GFAP nor a specific neural nuclei marker, NeuN, in the spinal dorsal horn of nerve-ligated mice. The present data strongly support the idea that spinal cord astrocytes and microglia are activated under the neuropathic pain-like state, and that the proliferated and activated microglia directly contribute to the development of a neuropathic pain-like state in mice.
引用
收藏
页码:1337 / 1348
页数:12
相关论文
共 45 条
[1]   Immune function of microglia [J].
Aloisi, F .
GLIA, 2001, 36 (02) :165-179
[2]   Tripartite synapses: glia, the unacknowledged partner [J].
Araque, A ;
Parpura, V ;
Sanzgiri, RP ;
Haydon, PG .
TRENDS IN NEUROSCIENCES, 1999, 22 (05) :208-215
[3]   PROPENTOFYLLINE (HWA-285) PROTECTS HIPPOCAMPAL-NEURONS OF MONGOLIAN GERBILS AGAINST ISCHEMIC DAMAGE IN THE PRESENCE OF AN ADENOSINE ANTAGONIST [J].
DELEO, J ;
SCHUBERT, P ;
KREUTZBERG, GW .
NEUROSCIENCE LETTERS, 1988, 84 (03) :307-311
[4]   Neuroprotection by tetracyclines [J].
Domercq, M ;
Matute, C .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2004, 25 (12) :609-612
[5]   Microglia as a source and target of cytokines [J].
Hanisch, UK .
GLIA, 2002, 40 (02) :140-155
[6]   Spinal glial activation and cytokine expression after lumbar root injury in the rat [J].
Hashizume, H ;
DeLeo, JA ;
Colburn, RW ;
Weinstein, JN .
SPINE, 2000, 25 (10) :1206-1217
[7]   Glia: Listening and talking to the synapse [J].
Haydon, PG .
NATURE REVIEWS NEUROSCIENCE, 2001, 2 (03) :185-193
[8]   Extracellular ATP triggers tumor necrosis factor-α release from rat microglia [J].
Hide, I ;
Tanaka, M ;
Inoue, A ;
Nakajima, K ;
Kohsaka, S ;
Inoue, K ;
Nakata, Y .
JOURNAL OF NEUROCHEMISTRY, 2000, 75 (03) :965-972
[9]   INTRATHECAL MORPHINE IN MICE - A NEW TECHNIQUE [J].
HYLDEN, JLK ;
WILCOX, GL .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1980, 67 (2-3) :313-316
[10]   Neuronal plasticity and signal transduction in nociceptive neurons: Implications for the initiation and maintenance of pathological pain [J].
Ji, RR ;
Woolf, CJ .
NEUROBIOLOGY OF DISEASE, 2001, 8 (01) :1-10