Activation of spinal serotonin2A/2C receptors augments nociceptive responses in the rat

Kjørsvik, Anne; Tjølsen, Arne; Hole, Kjell

doi:10.1016/s0006-8993(01)02652-x

Cited by 43 publications

(17 citation statements)

References 9 publications

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“…The case of spinal 5-HT 2 (Nakai et al, 2010) and 5-HT 7 (Brenchat et al, 2010(Brenchat et al, , 2012 receptors has been controversial. Furthermore, activation of spinal 5-HT 2 (Kjorsvik et al, 2001;Rahman et al, 2011), 5-HT 3 ), 5-HT 6 (Castan˜eda-Corral et al, 2009) and 5-HT 7 (Rocha-Gonza´lez et al, 2005 receptors increases acute nociceptive behavior. The role of spinal 5-HT 4 receptors in acute or chronic pain is unknown.…”

Section: Introductionmentioning

confidence: 99%

Secondary mechanical allodynia and hyperalgesia depend on descending facilitation mediated by spinal 5-HT4, 5-HT6 and 5-HT7 receptors

et al. 2012

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Section: Introductionmentioning

confidence: 99%

Secondary mechanical allodynia and hyperalgesia depend on descending facilitation mediated by spinal 5-HT4, 5-HT6 and 5-HT7 receptors

et al. 2012

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“…The serotonergic signal then descends the to the dorsal horn of spinal cord where it excites inhibitory interneurons that prevent the pain signal to reach the brain. This may relevant to the biology of addiction disorders as far as the mu-opioid receptors are likely involved in this mechanism [Renn and Dorsey, 2005;Dobner, 2006;Knyihar and Csillik, 2006;Rasche et al, 2006], and enhanced serotonin tone is known to be related to an antinociceptive action, specifically through receptors 2C, 1A, and 3 [Bardin et al, 2000;Kjorsvik et al, 2001;Wu et al, 2001;Obata et al, 2003Obata et al, , 2004Obata et al, , 2007Girard et al, 2006;Honda et al, 2006;Nakae et al, 2008]. Conflicting findings can be retrieved as well: Ogata and coworkers reported that tramadol, a well-known antinociceptive remedy, acts as a competitive inhibitor at HTR2C.…”

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confidence: 99%

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Drago

Serretti

2009

American J of Med Genetics Pt B

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HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

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“…For example, it was reported that the activation of the spinal 5-HT 2 receptor prior to peripheral inflammation results in an enhanced central transmission of nociceptive signals, suggesting that the 5-HT 2 receptor is involved in the excitation of neurons in the dorsal horn. Further, Kjorsvik et al [30,31] have demonstrated that the 5-HT 2 receptor agonist, (B)-2,5-dimethoxy-4-iodoamphetamine, when injected i.t., induces a dose-related biting and scratching behavior similar to that induced by the EAA receptor agonists, NMDA and AMPA. The spinal 5-HT 2 receptors have also been found to exert a facilitating effect on glutamatergic transmission in the dorsal horn.…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive Effects of Methysergide in Various Pain Models

et al. 2003

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Several studies have demonstrated that the nonselective opioid receptor antagonist naloxone produces a paradoxical antinociception in the formalin test. The opioid system is related to the serotonergic system for producing antinociception at the spinal level. Here we also asked whether systemic (i.p.) and intrathecal (i.t.) administrations of a nonselective serotonergic antagonist, methysergide, might produce paradoxical antinocicpetion similar to naloxone in the mouse formalin test. A diluted formalin solution was injected into the mouse plantar region of the hind paw and the duration of licking responses was measured at periods of 0–5 min (1st phase) and 20–40 min (2nd phase) after formalin injection. Methysergide administered i.p. and i.t. showed an attenuated licking duration only in the 2nd phase. The effect observed in the 2nd phase was reversed in the 5,7-dihydroxytriptamine, but not N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine pretreated group of mice, suggesting that descending serotonergic, but not noradrenergic, systems are involved in the methysergide antinociception. To further investigate the mechanism by which methysergide inhibited the nociceptive behaviors induced by formalin, the antinociceptive effect of methysergide was also tested in substance P (i.t.) and excitatory amino acids (i.t.), such as glutamate, N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainic acid, which are major components in the formalin-induced nociceptive transmission in the spinal cord pain models. The duration of nociceptive behaviors shown in these models was significantly shortened by i.p. and i.t. administration of methysergide. These results suggest that methysergide also produces a paradoxical antinociception in various pain models including the formalin test, similar to the results of naloxone.

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Activation of spinal serotonin2A/2C receptors augments nociceptive responses in the rat

Cited by 43 publications

References 9 publications

Secondary mechanical allodynia and hyperalgesia depend on descending facilitation mediated by spinal 5-HT4, 5-HT6 and 5-HT7 receptors

Secondary mechanical allodynia and hyperalgesia depend on descending facilitation mediated by spinal 5-HT4, 5-HT6 and 5-HT7 receptors

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Antinociceptive Effects of Methysergide in Various Pain Models

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