EVIDENCE FOR A ROLE FOR BULBOSPINAL PATHWAYS IN THE SPINAL ANTINOCICEPTIVE EFFECT OF SYSTEMICALLY ADMINISTERED VAPREOTIDE IN NORMAL RATS

Numerous neurotransmitters are involved in nociceptive transmission or regulation. Several reports have shown the analgesic effects of somat ostatin and its analogues. Somatostatin, when given intrathecally, mar kedly reduced pain in cancer patients. Somatostatin analogues that pos sess a longer half-life time are more convenient for therapeutic use. Vapreotide, a somatostatin analogue, was shown to induce a long-lastin g antinociceptive effect in rats. We studied the site and the mechanis m of action of vapreotide in rats using the paw pressure test. Intrath ecal administration of vapreotide induced no antinociception. Systemic ally administered vapreotide-induced antinociception was inhibited by several intrathecal (it) administered antagonists (yohimbine, naloxone and to a lesser degree tropisetron). These results show a lack of spi nal effect and suggest a supraspinal site of action with an involvemen t of noradrenergic and to a lesser degree serotonergic bulbospinal pat hways. In addition, spinal opioid receptors also seem to be involved. (C) 1998 Elsevier, Paris.