GABAergic pathway in a rat model of chronic neuropathic pain: modulation after intrathecal transplantation of a human neuronal cell line.
Current understanding of chronic pain points a decrease in level of the inhibitory neurotransmitter GABA, in the spinal dorsal horn, leading to an imbalance between excitatory and inhibitory pathways. A subcloned derivative of the human NT2 cell line (hNT2.17) which, after neuronal differentiation, secretes different inhibitory neurotransmitters such as GABA and glycine has been recently isolated. In this study, we have investigated the effect of this new cell line on peripheral nerve injury induced by chronic constriction (CCI) and notably the effect on the cellular GABAergic pathway. Our data show that the decrease in GABA expression in the spinal dorsal horn of injured animals is concomitant with a decline of its synthetic enzyme GAD67-Ir and mRNA but not GAD65. Interestingly, in transplanted animals we observed a strong induction of GAD67 mRNA with one week after graft, which is followed by a recovery of GAD67 and GABA Ir. This effect paralleled a reduction of hindpaw hypersensitivity and thermal hyperalgesia induced by CCI. These results suggest that hNT2.17 GABA cells can modulate neuropathic pain after CCI certainly by minimizing the imbalance and restoring the cellular GABAergic pathway.
Laboratory of Approches expérimentales et Thérapeutiques des Douleurs Neuropathiques, 133 route de Narbonne, 31062 Toulouse, France.
L
L
Vaysse
J C
JC
Sol
Y
Y
Lazorthes
M
M
Courtade-Saidi
M J
MJ
Eaton
S
S
Jozan
D000818:Animals; D002460:Cell Line; D002908:Chronic Disease; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008161:Lumbosacral Region; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000601:surgery*; D009474:Neurons / Q000378:metabolism / Q000637:transplantation*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1