Stimulation of spinal 5-HT2A/2C receptors potentiates the capsaicin-induced in vivo release of substance P-like immunoreactivity in the rat dorsal horn

• Published in: Brain research 2003-10, Vol.987 (1), p.10-16
• Main Authors: BERTELSEN, Anne Kjørsvik, ABDULLAHI WARSAME AFRAH, GUSTAFSSON, Henrik, TJØLSEN, Arne, HOLE, Kjell, STILLER, Carl-Olav
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)03216-5

Stimulation of spinal serotonin (5-HT)2A/2C receptors has previously been reported to lead to either a pro-nociceptive or an anti-nociceptive response. Behavioral data have indicated that the pro-nociceptive effect is related to the release of substance P (SP). The aim of this in vivo microdialysis study was to investigate if stimulation of spinal 5-HT2A/2C receptors by the selective agonist ( plus or minus )-2,5-dimethoxy-4-iodoamphetamine (DOI) induces spontaneous or capsaicin-evoked increase in the release of SP-like immunoreactivity (SP-LI) in the rat dorsal horn. A dose of capsaicin (25 mu M in the perfusion medium administered for 30 min), which did not lead to a significant release of SP-LI on its own, induced a significant increase of greater than 4-fold of the SP-LI level following spinal application of 50 nmol DOI. Higher (500 nmol) or lower (5 nmol) doses of DOI failed to induce a similar effect. In rats with a peripheral inflammation, induced by carrageenan, capsaicin (25 mu M) induced a non-significant increase of SP-LI. A significant 8-fold increase of the SP-LI level was detected following administration of 50 nmol DOI in combination with capsaicin. The effect of DOI, which was completely prevented by co-administration of the 5-HT2A receptor antagonist ketanserin in control animals without peripheral inflammation, was only partly blocked in animals with carrageenan induced peripheral inflammation. In conclusion, stimulation of 5-HT2A/2C receptors facilitates the capsaicin-evoked release of SP-LI in the dorsal horn in both animals with and without carrageenan-induced unilateral inflammation. The observation that the highest dose of DOI failed to induce SP-LI release may be due to an inhibitory postsynaptic action at this dose.