The purpose of this study was to investigate the effect of somatostatin (SST) in peripheral nerve terminals using local application of the SST receptor (SSTR) antagonist cyclo-somatostatin (c-SOM) injected into the receptive fields of cutaneous afferent fibers innervating the dorsal hairy skin in anesthetized rats. Single unit activity was recorded in teased filaments from the dorsal cutaneous nerve branch. Recordings were obtained from 206 primary afferent fibers. They were classified as C (n=70), Adelta (n=84) or Abeta (n=52) fibers based upon their conduction velocity. For C and Adelta fibers, mean discharge rate increased and mechanical threshold decreased significantly to 10 microL of 12.8 and 128 microM injected subcutaneously, but not to 0.128 and 1.28 microM c-SOM injection. For Abeta fibers, no dose of c-SOM changed their discharge rate or their mechanical sensitivity. In control experiments, injection of normal saline (NS) had no effect on any of the units tested. Octreotide (20 microM, 10 microL), an SSTR agonist, successfully reversed the increase in discharge rates and the decrease in mechanical thresholds in C and Adelta fibers when it was pre-administrated into the receptive field before c-SOM injection. These results provide evidence that somatostatin tonically inhibits the peripheral nerve terminals of small-diameter cutaneous afferent fibers.