Lack of Reciprocity between Opioid and 5-HT3 Receptors for Antinociception in Rat Spinal Cord

We examined the properties of the drug interaction between morphine and 5-HT3 receptor antagonist at the spinal level. The nociceptive state was induced by subcutaneously injecting formalin solution (5%, 50 µl) into the hindpaw of the rats. Intrathecal morphine and m-CPBG (5-HT3 receptor agonist) dose-dependently decreased the flinching response during phase 1 and phase 2 in the formalin test. Intrathecal 5-HT3 receptor antagonists (LY-278,584 and ondansetron) did not reverse the antinociceptive effect of intrathecal morphine. Intrathecal naloxone had little effect on attenuation of the antinociception of intrathecal m-CPBG. Taken together, no reciprocal interaction was noted between 5-HT3 receptor and opioid receptors at the spinal level. Thus, the 5-HT3 receptor antagonist may be useful to manage opioid-induced emesis at the spinal level.

[1]  H. Miranda,et al.  Spinal synergy between nonselective cyclooxygenase inhibitors and morphine antinociception in mice , 2005, Brain Research.

[2]  A. Dehpour,et al.  INVOLVEMENT OF N‐METHYL‐d‐ASPARTATE RECEPTORS and NITRIC OXIDE IN THE ROSTRAL VENTROMEDIAL MEDULLA IN MODULATING MORPHINE PAIN‐INHIBITORY SIGNALS FROM THE PERIAQUEDUCTAL GREY MATTER IN RATS , 2005, Clinical and experimental pharmacology & physiology.

[3]  J. Choi,et al.  Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats. , 2004, European journal of pharmacology.

[4]  C. Goodchild,et al.  Supraspinal and spinal cord opioid receptors are responsible for antinociception following intrathecal morphine injections , 2004, European journal of anaesthesiology.

[5]  W. A. Prado Antinociceptive potency of intrathecal morphine in the rat tail flick test: a comparative study using acute lumbar catheter in rats with or without a chronic atlanto-occipital catheter , 2003, Journal of Neuroscience Methods.

[6]  Long-chuan Yu,et al.  Involvement of oxytocin in spinal antinociception in rats with inflammation , 2003, Brain Research.

[7]  A. Yazigi,et al.  Prophylactic ondansetron is effective in the treatment of nausea and vomiting but not on pruritus after cesarean delivery with intrathecal sufentanil-morphine. , 2002, Journal of clinical anesthesia.

[8]  Keiji Ishizaki,et al.  Effects of 5-HT2 and 5-HT3 receptors on the modulation of nociceptive transmission in rat spinal cord according to the formalin test. , 2001, European journal of pharmacology.

[9]  R. Miledi,et al.  Distribution of serotonin 2A, 2C and 3 receptor mRNA in spinal cord and medulla oblongata. , 2001, Brain research. Molecular brain research.

[10]  T. Nishiyama Interaction between intrathecal morphine and glutamate receptor antagonists in formalin test. , 2000, European journal of pharmacology.

[11]  A. Eschalier,et al.  Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats , 2000, Pain.

[12]  Trevor Sharp,et al.  A review of central 5-HT receptors and their function , 1999, Neuropharmacology.

[13]  S. Khasabov,et al.  Modulation of afferent‐evoked neurotransmission by 5‐HT3 receptors in young rat dorsal horn neurones in vitro: a putative mechanism of 5‐HT3 induced anti‐nociception , 1999, British journal of pharmacology.

[14]  S. Fürst Transmitters involved in antinociception in the spinal cord , 1999, Brain Research Bulletin.

[15]  T. Brennan,et al.  Effect of Systemic and Intrathecal Morphine in a Rat Model of Postoperative Pain , 1997, Anesthesiology.

[16]  P. Fan Nonopioid mechanism of morphine modulation of the activation of 5-hydroxytryptamine type 3 receptors. , 1995, Molecular pharmacology.

[17]  X. Langlois,et al.  5-HT3 receptors in the rat central nervous system are mainly located on nerve fibres and terminals , 1993, Brain Research.

[18]  T. Crisp,et al.  Serotonin contributes to the spinal antinociceptive effects of morphine , 1991, Pharmacology Biochemistry and Behavior.

[19]  S. Bingham,et al.  The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity. , 1990, Canadian journal of physiology and pharmacology.

[20]  T. Crisp,et al.  A comparative analysis of monoaminergic involvement in the spinal antinociceptive action of DAMPGO and DPDPE , 1989, Pain.

[21]  D. Kellstein,et al.  Opioid-monoamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity , 1988, Pain.

[22]  M. Vogt,et al.  Involvement of 5-hydroxytryptamine-containing neurons in antinociception produced by injection of morphine into nucleus raphe magnus or onto spinal cord , 1984, Brain Research.

[23]  T. Matsumiya,et al.  Inhibitory effects of dorsal horn and excitant effects of ventral horn intraspinal microinjections of norepinephrine and serotonin in the cat. , 1981, Life sciences.

[24]  T. Yaksh,et al.  Spinal serotonin terminal system mediates antinociception. , 1979, The Journal of pharmacology and experimental therapeutics.

[25]  T. Yaksh,et al.  Chronic catheterization of the spinal subarachnoid space , 1976, Physiology & Behavior.

[26]  T. Gan Selective Serotonin 5-HT3 Receptor Antagonists for Postoperative Nausea and Vomiting , 2005, CNS drugs.

[27]  M. Tyers,et al.  Mechanism of the anti-emetic activity of 5-HT3 receptor antagonists. , 1992, Oncology.