Selective serotonin1A/1B agonists differentially affect spinal nociceptive reflexes

Meta‐chlorophenylpiperazine attenuates formalin‐induced nociceptive responses through 5‐HT1/2 receptors in both normal and diabetic mice

“…We thus hypothesized that the 5-hydroxytryptaminergic pathway involving 5-HT1 and 5-HT2 receptors plays an inhibitory role in not only acute but also chronic pain transmission. The former part of the speculation is in line with previous observations dealing with acute pain models (Zemlan et al, 1983;Eide & Tj0lsen, 1988;Murphy & Zemlan, 1990;Eide et al, 1990;El-Yassir & FleetwoodWalker, 1990;Crisp et al, 1991;Alhaider, 1991;Eide & Hole, 1991;Alhaider & Wilcox, 1993;Xu et al, 1994).…”

“…Although Fasmer et al (1986) showed that 8-OH-DPAT 1 mg kg-' s.c. (8-hydroxy-2-(di-n-propylamino)-tetralin; a 5-HTIA receptor agonist) elicited hypoalgesia in the acute phase of the formalin test, a non-specific effect might be responsible for the weak activity of 8-OH-DPAT compared with its strong affinity to the 5-HTlA receptor (Middlemiss & Fozard, 1983). Whereas it has been demonstrated that intrathecal administration of m-CPP (selective for 5-HTlB receptors over 5-HTlA receptors, Murphy & Zemlan, 1990) induces antinociception (Eide et al, 1990;Eide, 1992), and oral administration of the drug dose-dependently inhibited both phases of the formalin-induced nociceptive response, several lines of evidence suggest that there are multiple 5-HT1 binding sites in the spinal cord, and about 35% are specific for 5-HTIB, but the density of 5-HT2 receptors is very low in the spinal cord (Leysen et al, 1982;Monroe & Smith, 1983;Marlier et al, 1991). 5-HT2 binding sites have been demonstrated in the cortex (Hoyer et al, 1986;Molineaux et al, 1989), therefore activation of spinal 5-HTlB receptors and supraspinal 5-HT2 receptors might be involved in the antinociception.…”

Pharmacological characterization of serotonin receptor subtypes modulating primary afferent input to deep dorsal horn neurons in the neonatal rat

“…Previous studies that have demonstrated inhibitory actions of 5-HT 1B receptor agonists in the mature rat did not use CGS as the eective 5-HT 1B receptor agonist (e.g. Murphy & Zemlan, 1990;Ali et al, 1994;Xu et al, 1994;Gjerstad et al, 1997).…”

Evidence for a spinal serotonergic control of the peripheral inflammation in the rat

“…Although the physiological role of these serotonergic fibers has been mainly associated with analgesia, several studies of direct application of serotonin or selective serotonin receptor agonists and antagonists revealed that serotonin exerts both an inhibitory (Yaksh and Wilson, 1979;Hylden and Wilcox, 1983;Schmauss et al, 1983;Glaum et al, 1988) as well as a facilitatory (Fasmer et al, 1983;Hylden and Wilcox, 1983;Eide and Hole, 1988) effect on nociceptive transmission. In this way, the antinociceptive action of spinally-released serotonin has been reported to be mediated either by 5-HT 1 (Mjellem et al, 1992;Zemlan et al, 1994;Oyama et al, 1996) or 5-HT 3 (Glaum et al, 1988;Alhaider et al, 1991) type receptors, but other authors suggested both receptors as being responsible for a pronociceptive effect (Solomon and Gebhart, 1988;Millan et al, 1989;Murphy and Zemlan, 1990;Oyama et al, 1996;Green et al, 2000). Similarly, there is evidence for the involvement of spinal 5-HT 2 receptors both in the facilitation of the spinal nociceptive transmission (Sánchez et al, 1995;Kjorsvik et al, 2001) and in producing antinociception (Sasaki et al, 2001;Obata et al, 2002Obata et al, , 2003.…”