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 somatostatin and its analogues. Somatostatin, when given intrathecally, markedly reduced pain in cancer patients. Somatostatin analogues that possess a longer half-life time are more convenient for therapeutic use. Vapreotide, a somatostatin analogue, was shown to induce a long-lasting antinociceptive effect in rats. We studied the site and the mechanism of action of vapreotide in rats using the paw pressure test. Intrathecal administration of vapreotide induced no antinociception. Systemically administered vapreotide-induced antinociception was inhibited by several intrathecal (i.t.) administered antagonists (yohimbine, naloxone and to a lesser degree tropisetron). These results show a lack of spinal effect and suggest a supraspinal site of action with an involvement of noradrenergic and to a lesser degree serotonergic bulbospinal pathways. In addition, spinal opioid receptors also seen to be involved.
Berger
V
V
Equipe NPPUA, Laboratoire de Pharmacologie Médicale, Faculté de Médecine, Clermont-Ferrand, France.
Alloui
A
A
Kemeny
J L
JL
Dubray
C
C
Eschalier
A
A
Lavarenne
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D006614:Hindlimb; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*; D000077526:Tropisetron; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D007211:Indoles; D009292:Narcotic Antagonists; D012702:Serotonin Antagonists; C051458:vapreotide; D015016:Yohimbine; D009270:Naloxone; D013004:Somatostatin; D000077526:Tropisetron