Inhibition of thermal hyperalgesia and tactile allodynia by intrathecal administration of gamma-aminobutyric acid transporter-1 inhibitor NO-711 in rats with chronic constriction injury.
The present study was undertaken to explore the role of gamma-aminobutyric acid transporters in the neuropathic pain. On the chronic constriction injury (CCI) rats 4 doses (5, 10, 20, 40 microg in group N5, N10, N20, N40, respectively) of specific gamma-aminobutyric acid transporter-1 inhibitor NO-711 or normal saline (in group NS) were intrathecally administered before sciatic nerve ligation (pre-treatment) or at the third day after ligation (post-treatment). The paw withdrawl latency (PWL) from a noxious thermal stimulus and paw withdrawl mechanical threshold (PWMT) of von Frey filament was used as measure of thermal hyperalgesia and tactile allodynia respectively. The results demonstrated that post-treatment of NO-711 significantly suppressed thermal hyperalgesia and allodynia in CCI rats (P<0.05, P<0.01), the inhibitory effect lasted for 2 h (N40 group) and 4 h (N20 group) respectively. NO-711 inhibited thermal hyperalgesia induced by CCI in a dose-dependent manner. Intrathecal pretreatment with different doses of NO-711 delayed the occurrence of thermal hyperalgesia, but could not delay the emergence of allodynia induced by CCI. This study indicates that gamma-aminobutyric acid transporter inhibitor has anti-thermal hyperalgesia and anti-tactile allodynia effects in neuropathic rats.
Zhu
Shan-Shan
SS
Department of Anesthesiology, the First Affiliated Hospital, China Medical University, Shenyang 110001, China. xzzss2004@yahoo.com.cn
Zeng
Yin-Ming
YM
Wang
Jun-Ke
JK
Yan
Rong
R
Nie
Xin
X
Cao
Jun-Li
JL
D000818:Animals; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D010091:Oximes / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000503:physiopathology*
D018756:GABA Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010091:Oximes; C078793:NNC 711