Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain

被引:404
作者
Schwei, MJ
Honore, P
Rogers, SD
Salak-Johnson, JL
Finke, MP
Ramnaraine, ML
Clohisy, DR
Mantyh, PW
机构
[1] Univ Minnesota, Neurosyst Ctr, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Prevent Sci, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA
[5] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA
[6] Univ Minnesota, Dept Orthopaed Surg, Minneapolis, MN 55455 USA
[7] Vet Adm Med Ctr, Minneapolis, MN 55417 USA
关键词
astrocyte; gliosis; nociception; primary afferents; sensitization; osteolysis;
D O I
10.1523/JNEUROSCI.19-24-10886.1999
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.
引用
收藏
页码:10886 / 10897
页数:12
相关论文
共 116 条
[91]   GLUTAMATE INDUCES THE GROWTH-FACTORS NGF, BFGF, THE RECEPTOR FGF-R1 AND C-FOS MESSENGER-RNA EXPRESSION IN RAT ASTROCYTE CULTURE [J].
PECHAN, PA ;
CHOWDHURY, K ;
GERDES, W ;
SEIFERT, W .
NEUROSCIENCE LETTERS, 1993, 153 (01) :111-114
[92]   Breakthrough pain: characteristics and impact in patients with cancer pain [J].
Portenoy, RK ;
Payne, D ;
Jacobsen, P .
PAIN, 1999, 81 (1-2) :129-134
[93]   Management of cancer pain [J].
Portenoy, RK ;
Lesage, P .
LANCET, 1999, 353 (9165) :1695-1700
[94]   INSITU HYBRIDIZATION HISTOCHEMISTRY AND IMMUNOCYTOCHEMISTRY REVEAL AN INCREASE IN SPINAL DYNORPHIN BIOSYNTHESIS IN A RAT MODEL OF PERIPHERAL INFLAMMATION AND HYPERALGESIA [J].
RUDA, MA ;
IADAROLA, MJ ;
COHEN, LV ;
YOUNG, WS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (02) :622-626
[95]   CONTRIBUTION OF INTERLEUKIN-1-BETA TO THE INFLAMMATION-INDUCED INCREASE IN NERVE GROWTH-FACTOR LEVELS AND INFLAMMATORY HYPERALGESIA [J].
SAFIEHGARABEDIAN, B ;
POOLE, S ;
ALLCHORNE, A ;
WINTER, J ;
WOOLF, CJ .
BRITISH JOURNAL OF PHARMACOLOGY, 1995, 115 (07) :1265-1275
[96]   REGULATION OF INTERLEUKIN-6 PRODUCTION BY CAMP-PROTEIN KINASE-A PATHWAY IN RAT CORTICAL ASTROCYTES [J].
SCHETTINI, G ;
GRIMALDI, M ;
NAVARRA, P ;
POZZOLI, G ;
REICHLIN, S ;
PREZIOSI, P .
PHARMACOLOGICAL RESEARCH, 1994, 30 (01) :13-24
[97]  
Shafer RA, 1997, GLIA, V21, P370, DOI 10.1002/(SICI)1098-1136(199712)21:4<370::AID-GLIA4>3.0.CO
[98]  
2-7
[99]   PLASTICITY OF ASTROCYTES [J].
SHAO, YP ;
MCCARTHY, KD .
GLIA, 1994, 11 (02) :147-155
[100]  
Shibata T, 1997, J NEUROSCI, V17, P9212