Tonic control of peripheral cutaneous nociceptors by somatostatin receptors

The peptide somatostatin [somatotropin release-inhibiting factor (SRIF)] is widely distributed in the body and exerts a variety of hormonal and neural actions. Several lines of evidence indicate that SRIF is important in noci ceptive processing: (1) it is localized in a subset of small-diameter dorsa l root ganglion cells; (2) activation of SRIF receptors results in inhibiti on of both nociceptive behaviors in animals and acute and chronic pain in h umans; (3) SRIF inhibits dorsal horn neuronal activity; and (4) SRIF reduce s responses of joint mechanoreceptors to noxious rotation of the knee joint . The goal of the present study is to show that cutaneous nociceptors are u nder the tonic inhibitory control of SRIF. This is accomplished using behav ioral and electrophysiological paradigms. In a dose-dependent manner, intra plantar injection of the SRIF receptor antagonist cyclo-somatostatin (c-SOM ) results in nociceptive behaviors in normal animals and enhancement of noc iceptive behaviors in formalin-injected animals, and these actions can be b locked when c-SOM is coapplied with three different SRIF agonists. Furtherm ore, intraplantar injection of SRIF antiserum also results in nociceptive b ehaviors. Electrophysiological recordings using an in vitro glabrous skin-n erve preparation show increased nociceptor activity in response to c-SOM, a nd this increase is blocked by the same three SRIF agonists. Parallel behav ioral and electrophysiological studies using the opioid antagonist naloxone demonstrate that endogenous opioids do not maintain a tonic inhibitory con trol over peripheral nociceptors, nor does opioid receptor antagonism influ ence peripheral SRIF effects on nociceptors. These findings demonstrate tha t SRIF receptors maintain a tonic inhibitory control over peripheral nocice ptors, and this may contribute to mechanisms that control the excitability of these terminals.