SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model

被引:199
作者
Tanaka, M
Cummins, TR
Ishikawa, K
Dib-Hajj, SD
Black, JA
Waxman, SG
机构
[1] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
[2] Vet Adm Med Ctr, Neurosci Res Ctr, EPVA, PVA, W Haven, CT 06516 USA
关键词
carrageenan; dorsal root ganglion; inflammatory pain; in situ hybridization; rat; alpha-SNS sodium channel; whole-cell patch-clamp;
D O I
10.1097/00001756-199804200-00003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
IT has been suggested that hyperexcitability in dorsal root ganglion (DRG) neurons due to altered sodium channel expression contributes to some chronic pain syndromes. To understand the role of the voltage-gated sodium channel alpha-SNS in inflammatory pain, we investigated the expression of alpha-SNS mRNA and tetrodotoxin-resistant (TTX-R) sodium current in small DRG neurons, which include nociceptive cells, following injection of carrageenan into the hind paw of the rat using in situ hybridization and patch-clamp recording. alpha-SNS mRNA expression in DRG neurons projecting to the inflamed limb was significantly increased 4 days following carrageenan injection, compared with DRG neurons from the contralateral side or naive (uninjected) rats (mean +/- s.d. optical density ratio: ipsilateral/contralateral, 1.77 +/- 0.17; ipsilateral/naive, 1.88 +/- 0.36). The amplitude of the TTX-R sodium current in small DRG neurons projecting to the inflamed limb was significantly larger than on the contralateral side 4 days post-injection (31.7 +/- 3.3 us 20.0 +/- 2.1 nA). The TTX-R current density was also significantly increased. These results demonstrate the increased expression of alpha-SNS sodium channels in small DRG neurons following injection of carrageenan into their projection field, and suggest that alpha-SNS is involved in the development of hyperexcitability associated with inflammation. (C) 1998 Rapid Science Ltd.
引用
收藏
页码:967 / 972
页数:6
相关论文
共 28 条
[1]  
AKOPIAN AN, 1996, NATURE, V379, P258
[2]  
BALCK JA, 1997, NEUROREPORT, V8, P2331
[3]   Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs [J].
Black, JA ;
DibHajj, S ;
McNabola, K ;
Jeste, S ;
Rizzo, MA ;
Kocsis, JD ;
Waxman, SG .
MOLECULAR BRAIN RESEARCH, 1996, 43 (1-2) :117-131
[4]   3 TYPES OF SODIUM-CHANNELS IN ADULT-RAT DORSAL-ROOT GANGLION NEURONS [J].
CAFFREY, JM ;
ENG, DL ;
BLACK, JA ;
WAXMAN, SG ;
KOCSIS, JD .
BRAIN RESEARCH, 1992, 592 (1-2) :283-297
[5]   Inflammation reveals inhibition of noxious responses of rat spinal neurones by carbamazepine [J].
Chapman, V ;
Dickenson, AH .
NEUROREPORT, 1997, 8 (06) :1399-1404
[6]  
Cummins TR, 1997, J NEUROSCI, V17, P3503
[7]   NEURONAL GROWTH-FACTOR REGULATION OF 2 DIFFERENT SODIUM-CHANNEL TYPES THROUGH DISTINCT SIGNAL-TRANSDUCTION PATHWAYS [J].
DARCANGELO, G ;
PARADISO, K ;
SHEPHERD, D ;
BREHM, P ;
HALEGOUA, S ;
MANDEL, G .
JOURNAL OF CELL BIOLOGY, 1993, 122 (04) :915-921
[8]   Down-regulation of transcripts for Na channel alpha-SNS in spinal sensory neurons following axotomy [J].
DibHajj, S ;
Black, JA ;
Felts, P ;
Waxman, SG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (25) :14950-14954
[9]   INFLAMMATORY MEDIATORS OF PAIN [J].
DRAY, A .
BRITISH JOURNAL OF ANAESTHESIA, 1995, 75 (02) :125-131
[10]   Sodium channel accumulation in humans with painful neuromas [J].
England, JD ;
Happel, LT ;
Kline, DG ;
Gamboni, F ;
Thouron, CL ;
Liu, ZP ;
Levinson, SR .
NEUROLOGY, 1996, 47 (01) :272-276