Example Of Monoamines In Nociception

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Monoamines in Nociception
Serotonin (5-HT) and norepinephrine are primary neurotransmitters of the monoamine pathway and have been implicated in chronic pain (Bardin, 2011). These monoamines, particularly in areas such as the PAG, form a depression-pain interface. The PAG takes information sent from the amygdala, neocortex, and hypothalamus, processes the information, and then sends the modified signals to the brainstem, particularly the RVM (Millan, 2002). Approximately 20% of the neurons within the RVM are serotoninergic. Depending on the receptor, dose, and chronology, 5-HT within the CNS can be either pro- or antinociceptive (Bannister et al., 2009). As such 5-HT's influence on pain modulation can be quite complex.
5-HT3 receptors in
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Activation of prefrontal 5-HT2A receptors is associated with elevated mood and improvement in several forms of cognitive function (Fisher et al., 2009; Vollenweider, Vontobel, Hell, & Leenders, 1999; Williams, Rao, & Goldman-Rakic, 2002). Estrogen can increase the density of these receptors in the brain in rats (Summer & Fink, 1995). In post-menopausal human women estrogen replacement therapy increases 5-HT2A binding in prefrontal areas of the brain (Kugaya et al., 2003).
In the raphe nucleus and spinal cord, 5-HT1A receptor activation is associated with inhibition of nociception (Bardin, Tarayre, Malfetes, Koek, & Colpaert, 2003; Mico, Berrocoso, Ortega-Alvaro, Gibert-Rahola, & Rojas-Corrales, 2006). Though not yet tested in humans, tests in laboratory animals suggest that certain 5-HT1A agonists rival morphine in their ability to inhibit pain (Colpaert, 2006). Estrogens rapidly downregulate activity in these receptors in the brain in short terms (Mize, Poisner, & Alper, 2001) while long-term low estrogen concentration also decrease 5-HT1A receptor binding in many areas of the brain (Le Saux & Di Paolo, 2005).
More recently discovered and less well understood, the 5-HT7 receptor in the spinal cord and thalamus appear to modulate nociception (Bannister, Lockwood, Goncalves, Patel, & Dickenson, 2017; Dogrul, Ossipov, & Porreca, 2009). Intrathecal injections of 5-HT were shown to have
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