Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors

Somatostatin (SST) is in primary afferent neurons and reduces vascular and nociceptive components of inflammation. SST receptor (SSTR) agonists provid e analgesia following intrathecal or epidural administration in humans, but neurotoxicity in the central nervous system (CNS) has been reported in exp erimental animals. With the rationale that targeting peripheral SSTRs would provide effective analgesia while avoiding CNS side effects, the goals of the present study are to investigate the presence of SSTRs on peripheral pr imary afferent fibers and determine the behavioral and physiological effect s of the SST agonist octreotide (OCT) on formalin-induced nociception and b radykinin-induced primary afferent excitation and sensitization in the rat. The results demonstrate that: (1)SSTR2as are present on 11% of peripheral primary afferent sensory fibers in rat glabrous skin (2) intraplantar injec tion of OCT reduces formalin-induced nociceptive behaviors; (3) OCT reduces . in a dose-dependent fashion, responses to thermal stimulation in C-mechan oheat sensitive fibers; and (4) OCT reduces the responses of C-mechonoheat fibers to bradykinin-induced excitation and sensitization to heat. Each of these actions can be reversed following co-injection of OCT with the SSTR a ntagonist cyclo-somatostatin (c-SOM). Thus, activation of peripheral SSTRs reduces both inflammatory pain and the activity of sensitized nociceptors, avoids deleterious CNS side effects and may be clinically useful in the tre atment of pain of peripheral origin. (C) 2001 international Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.