Research of Neural Network in Spinal Dorsal Horn and Neuropathic Pain

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Responses of membrane currents to substance P (SP) have well been examined in spinal dorsal horn neurons, but little is known about those to calcitonin gene-related peptide (CGRP) and somatostatin (STT). Therefore, we addressed these issues in freshly sliced spinal cord of rats (3-4 weeks) by using the blind patch clamp techniques.Of the dorsal horn neurons (42/68 cells) in the deep lamina (III-VI), about 60% showed the slow inward current by the bath application of SP (1 μM). These currents have been considered to be evoked though G protein-coupled SP receptors. Many of these neurons simultaneously increased excitatory post-synaptic currents (EPSCs). About 30% of deep dorsal horn neurons (12/39 cells) showed the slow inward current by the application of CGRP (1μM). The slow inward current by CGRP (n=1) was observed in the presence of tetrodotoxin (TTX, 1μM), suggesting that the currents are evoked though the G protein-coupled CGRP receptors on patched the neurons. The directly responsive neurons to CGRP always displayed the slow inward current by SP. However, the mean amplitude of these currents by CGRP was smaller than those by SP. On the other hand, the application of STT (1μM) induced the slow outward currents in about 30% of the patched deep dorsal horn neurons (9/31 cells). This outward current by STT (n=1) was also observed in the presence of tetrodotoxin (TTX, 1μM) (data not shown). Many these neurons also showed the slow inward current by SP. The slow outward currents were not suppressed by the repetitive application of STT, although the slow inward currents by SP and CGRP were desensitized.The present study suggests that CGRP and STT, in addition to SP, play important roles in synaptic transmission to deep dorsal horn neurons.