title: Presynaptic facilitation by tetracaine of glutamatergic spontaneous excitatory transmission in the rat spinal substantia gelatinosa - Involvement of TRPA1 channels.
abstract: The amide-type local anesthetic (LA) lidocaine activates transient receptor potential (TRP) ankyrin-1 (TRPA1) channels to facilitate spontaneous l-glutamate release onto spinal substantia gelatinosa (SG) neurons, which play a crucial role in regulating nociceptive transmission. In contrast, the ester-type LA procaine reduces the spontaneous release of l-glutamate in SG neurons. In order to determine whether TRPA1 activation by LAs is specific to amide-types, we examined the actions of tetracaine, another ester-type LA, and other amide-type LAs on glutamatergic spontaneous excitatory transmission in SG neurons by focusing on TRP activation. Whole-cell patch-clamp recordings were performed on SG neurons of adult rat spinal cord slices at a holding potential of -70mV. Bath-applied tetracaine increased spontaneous excitatory postsynaptic current (sEPSC) frequency in a concentration-dependent manner. Tetracaine activity was resistant to the voltage-gated Na+-channel blocker tetrodotoxin, the TRP vanilloid-1 antagonist capsazepine, and the TRP melastatin-8 antagonist BCTC, but was inhibited by the non-selective TRP antagonist ruthenium red and the TRPA1 antagonist HC-030031. With respect to amide-type LAs, prilocaine had a tendency to increase sEPSC frequency, while ropivacaine and levobupivacaine reduced the frequency. In conclusion, tetracaine facilitated spontaneous l-glutamate release from nerve terminals by activating TRPA1 channels in the SG, resulting in an increase in the excitability of SG neurons. TRPA1 activation was not specific to amide-type or ester-type LAs. The facilitatory action of LAs may be involved in pain occurring after recovery from spinal anesthesia.
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Piao
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. Electronic address: kumamote@cc.saga-u.ac.jp.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D000077554:Levobupivacaine; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010146:Pain / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011318:Prilocaine / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D012430:Ruthenium Red / Q000494:pharmacology; D013376:Substantia Gelatinosa / Q000187:drug effects* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism*; D013748:Tetracaine / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D000577:Amides; D000779:Anesthetics, Local; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D018377:Neurotransmitter Agents; D011687:Purines; D011719:Pyrazines; D011725:Pyridines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D011318:Prilocaine; D013748:Tetracaine; D012430:Ruthenium Red; D018698:Glutamic Acid; D013779:Tetrodotoxin; D000077212:Ropivacaine; D000077554:Levobupivacaine; C071423:capsazepine; D002211:Capsaicin; D002045:Bupivacaine
keywords: Pain; Spinal dorsal horn; Spontaneous excitatory transmission; TRPA1 channel; Tetracaine