The aim of the present study is to investigate the effect of somatostatin (SST). It is well known that SST is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings indicate a role for SST in the central processing of nociception. Therefore, we tested the hypothesis whether a local release of SST modulates the tooth-pulp (TP)-evoked upper cervical spinal dorsal horn (C(1)) neuronal activity, using microiontophoretic application and immunohistochemical techniques. Extracelluar single unit recordings were made from 35 C(1) neurons responding to TP electrical stimulation (TPS) in pentobarbital anesthetized rats. Microiontophoretic application of SST (30-70 nA) current dependently inhibited TP-evoked C(1) neuronal discharges (60%, 21/35). The inhibition of this discharge by 50 nA SST application was abolished by co-application of a SST(2) receptor antagonist (Cyanamid-154806, 50 nA). Immunoreactivity for SST(2A) receptor was found in the superficial layer (Iota-IotaIotaIota) of C(1) dorsal horn. These results suggest that a local release of SST modulates the TP-evoked C(1) neuronal activity and this may contribute to a useful therapeutic target for the alleviation of tooth pain and trigeminal hyperalgesia.