Paper - WANFANG MED ONLINE

You Position: Home > Paper

Suppressing SNAP-25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission

( views:113, downloads:12 )

Author:: No author available

Journal Title:: Chinese Medical Journal

Issue:: 21

DOI:: 10.3760/cma.j.issn.0366-6999.20130967

Key Word:: neuropathic pain;SNAP-25;glia glutamate transporter;gamma aminobutyric acid transporter;neurotransmission

Abstract： Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level.The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters,which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT).Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission.SNAP-25,which is one of the SNARE complexes,can modulate the release of neurotransmitters.Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS.The role of SNAP-25 and GLT as well as GAT is not clearly understood.Methods We used the rat chronic constriction injury (CCI) model for research,and degraded SNAP-25 by a single intrathecal administration of BoNT/A.The mechanical (MWT) and thermal withdrawal latency (TWL) were tested.The level of SNAP-25,GLT,and GAT-1 were assayed using RT-PCR and Western blotting.Results SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP-25 was correlated with the relief of nociceptive responses in CCI rats.MWT and TWL returned to normal from the 5th to 14th day (P ＜0.05) after the administration.On the 14th day after surgery,compared to the sham group,the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P ＜0.05).The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.Conclusions SNAP-25 and GLT play important roles in the development of neuropathic pain,and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury.Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI,but had no significant effect on the expression of GAT-1.

Reference

[1]G J, Bennett,Y K, Xie.A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.[J].1988,33.
[2]Qing-Xiang Mao,Tian-De Yang.Amitriptyline upregulates EAAT1 and EAAT2 in neuropathic pain rats[J].2010,81(4-5).
[3]Watkins LR,Milligan ED.Pathological and protective roles of glia in chronic pain.[J].2009,10(1).
[4]Sakaba, T,Stein, A,Jahn, R,etc.Distinct kinetic changes in neurotransmitter release after SNARE protein cleavage[J].2005,309(5733).
[5]Danbolt NC.Glutamate uptake.[J].2001,65(1).
[6]Miyashita T,Valenzuela CF,Mameli M,etc.Expression and function of SNAP-25 as a universal SNARE component in GABAergic neurons.[J].2006,26(30).
[7]K A, Vyas,H V, Patel,A A, Vyas,etc.Segregation of gangliosides GM1 and GD3 on cell membranes, isolated membrane rafts, and defined supported lipid monolayers.[J].2001,382.
[8]Fan HP,Fan FJ,Bao L,etc.SNAP-25/syntaxin 1A complex functionally modulates neurotransmitter gamma-aminobutyric acid reuptake.[J].2006,281(38).
[9]Pozzi D,Coco S,Frassoni C,etc.Analysis of SNAP-25 immunoreactivity in hippocampal inhibitory neurons during development in culture and in situ.[J].2005,131(4).
[10]Song, Z.,Guo, Q.,Liu, C.,etc.Gene knockdown with lentiviral vector-mediated intrathecal RNA interference of protein kinase C gamma reverses chronic morphine tolerance in rats[J].2010,12(11).
[11]Nie H,Weng HR.Impaired glial glutamate uptake induces extrasynaptic glutamate spillover in the spinal sensory synapses of neuropathic rats.[J].2010,103(5).
[12]J, Jankovic,M F, Brin.Botulinum toxin: historical perspective and potential new indications.[J].1997,6.
[13]Ong WY,Ng CH.Increased synaptosomal (3H) GABA uptake in the rat brainstem after facial carrageenan injections.[J].2002,98(3).
[14]M, Zimmermann.Ethical guidelines for investigations of experimental pain in conscious animals.[J].1983,16.
[15]Bebber D,Gosselin RD,Decosterd I.Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain.[J].2010,480(2).
[16]G, Schiavo,C C, Shone,O, Rossetto,etc.Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin.[J].1993,268.
[17]Huang Y,Hackshaw KV,Stephens RL Jr,etc.Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model.[J].2005,1041(1).
[18]Andy Dray,Laszlo Urban,Anthony Dickenson.Pharmacology of chronic pain[J].1994,15(6).
[19]Boris Filipovic,Lidija Bach Rojecky,Zdravko Lackovic.Lasting reduction of postsurgical hyper algesia after single injection of botulinum toxin type A in rat[J].2010,24(1).
[20]Lim G,Sung B,Mao J.Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats.[J].2003,23(7).
[21]Hu Y,Li Q,Li L,etc.An anti-nociceptive role for ceftriaxone in chronic neuropathic pain in rats.[J].2010,148(2).
[22]Peter Jonas.The time course of signaling at central glutamatergic synapses[J].2000,15(2).
[23]Kitamura Y,Matsuka Y,Spigelman I,etc.Botulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction.[J].2009,159(4).
[24]T, S?llner,S W, Whiteheart,M, Brunner,etc.SNAP receptors implicated in vesicle targeting and fusion.[J].1993,362(6418).
[25]Hansson P,Rowbotham M,Sommer C,etc.NeuPSIG guidelines on neuropathic pain assessment.[J].2011,152(1).
[26]Hoogland G,Daemen MA,Cijntje JM.Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy.[J].2008,444(1).
[27]Coco S,Galli T,Proux Gillardeaux V,etc.SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization.[J].2004,41(4).
[28]Paluzzi S,Rossetto O,Verderio C,etc.Traffic of botulinum toxins A and E in excitatory and inhibitory neurons[J].2007,8(1).
[29]Lee WH,Shin TJ,Kim HJ,etc.Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice.[J].2011,112(1).