ラット脊髄後角膠様質細胞への侵害受容シナプス伝達に対するTRPA1チャネル作動薬の応答解析 ──In vitroおよびin vivoパッチクランプ解析を用いて──

歌 大介, 井本 敬二, 古江 秀昌

doi:10.11154/pain.32.179

The transient receptor potential ankyrin 1 (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 in vitro and in vivo whole–cell patch–clamp recordings in adult rat spinal cord. We have shown that cinnamaldehyde (CA; selective TRPA1 agonist) elicited a barrage of excitatory postsynaptic currents (EPSCs) in a subset of the SG neurons. However, the role of TRPA1 on synaptic transmission in the spinal dorsal horn is not fully understood. In this study, an action of CA was investigated on dorsal root–evoked synaptic transmission to SG neurons in adult rat spinal cord slices by use of the whole–cell voltage–clamp technique. In about 30% of neurons examined, superfusing CA depressed C–fiber–evoked EPSCs. On the contrary, Aδ–fiber–evoked EPSCs were unaffected by CA in all of cells tested. Such a blockade action was not observed when CA was applied in the presence of a specific TRPA1 antagonist, HC–030031. Next, we examined the effects of mechanical stimuli to the skin during TRPA1 activation in the spinal dorsal horn by using in vivo patch clamp technique. Superfusing CA significantly inhibited pinch evoked EPSCs of the skin.It is concluded that TRPA1 agonist CA specifically acts on a part of C–afferents, resulting in an inhibition of evoked excitatory transmission to the SG; this may contribute to, at least in part, an acute analgesic action of CA such as TRPV1 agonist capsaicin. These findings suggest that activation of spinal TRPA1 channels may have therapeutic potential for the treatment of pain.

ラット脊髄後角膠様質細胞への侵害受容シナプス伝達に対するTRPA1チャネル作動薬の応答解析 ──<i>In vitro</i>および<i>in vivo</i>パッチクランプ解析を用いて──

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