Anti-allodynic and promotive effect on inhibitory synaptic transmission of riluzole in rat spinal dorsal horn
| Autor: | Hiroshi Yamada, Ryo Taiji, Shunji Tsutsui, Terumasa Nakatsuka, Naoko Nishio, Wataru Taniguchi, Manabu Yamanaka |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Spinal dorsal horn
SNI spared nerve injury QH301-705.5 CCI chronic constriction injury Biophysics QD415-436 Neurotransmission Pharmacology Inhibitory postsynaptic potential Neuropathic pain Biochemistry chemistry.chemical_compound Mechanical allodynia medicine Nociception assay TTX tetrodotoxin Biology (General) Riluzole IPSC inhibitory postsynaptic current Strychnine Bicuculline SG substantia gelatinosa Nociception chemistry Research Article medicine.drug Nociceptive transmission |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 28, Iss, Pp 101130-(2021) Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | Riluzole (2-amino-6-(trifluoromethoxy)benzothiazole) is a drug known for its inhibitory effect on glutamatergic transmission and its anti-nociceptive and anti-allodynic effects in neuropathic pain rat models. Riluzole also has an enhancing effect on GABAergic synaptic transmission. However, the effect on the spinal dorsal horn, which plays an important role in modulating nociceptive transmission, remains unknown. We investigated the ameliorating effect of riluzole on mechanical allodynia using the von Frey test in a rat model of neuropathic pain and analyzed the synaptic action of riluzole on inhibitory synaptic transmission in substantia gelatinosa (SG) neurons using whole-cell patch clamp recordings. We found that single-dose intraperitoneal riluzole (4 mg/kg) administration effectively attenuated mechanical allodynia in the short term in a rat model of neuropathic pain. Moreover, 300 μM riluzole induced an outward current in rat SG neurons. The outward current induced by riluzole was not suppressed in the presence of tetrodotoxin. Furthermore, we found that the outward current was suppressed by simultaneous bicuculline and strychnine application, but not by strychnine alone. Altogether, these results suggest that riluzole enhances inhibitory synaptic transmission monosynaptically by potentiating GABAergic synaptic transmission in the rat spinal dorsal horn. Highlights • Riluzole shows anti-nociceptive and anti-allodynic effects in neuropathic pain models. • The spinal dorsal horn plays an important role in modulating nociceptive transmission. • Riluzole potentiated GABAergic synaptic transmission in the rat spinal dorsal horn. •Riluzole enhanced inhibitory synaptic transmission monosynaptically. |
| Databáze: | OpenAIRE |
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