title: TRPA1-expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord.
abstract: The TRPA1 channel has been proposed to be a molecular transducer of cold and inflammatory nociceptive signals. It is expressed on a subset of small primary afferent neurons both in the peripheral terminals, where it serves as a sensor, and on the central nerve endings in the dorsal horn. The substantia gelatinosa (SG) of the spinal cord is a key site for integration of noxious inputs. The SG neurons are morphologically and functionally heterogeneous and the precise synaptic circuits of the SG are poorly understood. We examined how activation of TRPA1 channels affects synaptic transmission onto SG neurons using whole-cell patch-clamp recordings and morphological analyses in adult rat spinal cord slices. Cinnamaldehyde (TRPA1 agonist) elicited a barrage of excitatory postsynaptic currents (EPSCs) in a subset of the SG neurons that responded to allyl isothiocyanate (less specific TRPA1 agonist) and capsaicin (TRPV1 agonist). Cinnamaldehyde evoked EPSCs in vertical and radial but not islet or central SG cells. Notably, cinnamaldehyde produced no change in inhibitory postsynaptic currents and nor did it produce direct postsynaptic effects. In the presence of tetrodotoxin, cinnamaldehyde increased the frequency but not amplitude of miniature EPSCs. Intriguingly, cinnamaldehyde had a selective inhibitory action on monosynaptic C- (but not Adelta-) fiber-evoked EPSCs. These results indicate that activation of spinal TRPA1 presynaptically facilitates miniature excitatory synaptic transmission from primary afferents onto vertical and radial cells to initiate action potentials. The presence of TRPA1 channels on the central terminals raises the possibility of bidirectional modulatory action in morphologically identified subclasses of SG neurons.
authors.affiliation: Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uta
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Furue
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pickering
authors.forename: Md Harunor
authors.initials: MH
authors.lastname: Rashid
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mizuguchi-Takase
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Katafuchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Imoto
authors.forename: Megumu
authors.initials: M
authors.lastname: Yoshimura
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D016587:Antimutagenic Agents / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D048430:Cell Shape; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005520:Food Preservatives / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology*; D013376:Substantia Gelatinosa / Q000166:cytology* / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels
chemical_list: D017487:Ankyrins; D016587:Antimutagenic Agents; D015220:Calcium Channels; D005520:Food Preservatives; D017879:Isothiocyanates; D018689:Sensory System Agents; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D000171:Acrolein; C004471:allyl isothiocyanate; D002211:Capsaicin; C012843:cinnamaldehyde