Alternative agents used to treat neuropsychiatric symptoms include serotonergic antidepressants, benzodiazepines, and anticonvulsant medications.
Other symptomatic interventions under investigation include serotonergic targets, such as 5-HT4[ 5] and a 5-HT6[ 6, 7].
These other mechanisms include the l-arginine-nitric oxide (l-arginine-NO) pathway, as well as endogenous opiate and serotonergic mechanisms.
Potential mechanisms include alterations to the pain-modulating dopaminergic system and carbergoline, an ergot derivative, also possesses significant affinity for certain subtypes of serotonergic and adrenergic receptors.
Although the exact mechanism of neuraxial opioid-induced pruritus is unclear, the postulated mechanisms include the presence of an "itch centre" in the central nervous system (CNS), medullary dorsal horn activation, antagonism of inhibitory transmitters, modulation of 5-hydroxytryptamine subtype 3 (5-HT3) or serotonergic pathways and the involvement of prostaglandins [ 3, 8].
When GABAergic neurons are activated, they inhibit the neurons with which they are connected, including serotonergic neurons.
This supports that the presence of descending axons, including serotonergic axons, augments motor neuron regeneration.
For example, volinanserin, a serotonin receptor antagonist, inhibited 41 different assays, the majority of which were GPCRs and transporters (78%), including the serotonergic system (affecting 9 out of 11 total serotonergic assays) (see Supporting Information, Table S2).
Among the above mechanisms, we assume that the medulla is substantially involved as a hub structure related to interictal WPH, because similar brainstem volume reduction and structural alteration [75, 76] were observed in migraine and FM, and it includes the serotonergic system from the rostral ventromedial medulla, which has been implicated in migraine and FM pathophysiology [80].
Common biochemical pathways and systems included the serotonergic, noradrenergic, dopaminergic, GABA-ergic, glutamatergic, opioid, alcohol metabolizing and nicotinic systems.
