Serotonin and noradrenaline reuptake inhibitors in animal models of pain

Abstract

Animal models of chronic pain serve as an experimental basis for testing new therapeutic interventions and for mechanistic investigations. In an animal model of chronic pain, based on the injection of formalin into the paw of a rodent, inhibitors of noradrenaline reuptake such as nisoxetine, nortriptyline and maprotiline and dual inhibitors of the noradrenaline and serotonin reuptake such as imipramine and milnacipran produce potent anti-nociceptive effects, whereas selective serotonin reuptake inhibitors, such as fluvoxamine, are much less potent. In another model, neuropathic pain resulting from the chronic constriction injury of the sciatic nerve was prevented by the dual uptake inhibitor, venlafaxine. The experimental model involving ligation of the 5th spinal nerve induces behavioural signs in rats and mice that are similar to the symptoms of human neuropathic pain. In this model amitriptyline, a non-selective serotonin and noradrenaline reuptake blocker, the preferential noradrenaline reuptake inhibitor, desipramine and the selective serotonin and noradrenaline reuptake inhibitors, milnacipran and duloxetine, produce a decrease in pain sensitivity whereas the selective serotonin reuptake inhibitor, fluoxetine, is ineffective. Antidepressants acting on the noradrenergic or both the noradrenergic and serotonergic systems thus appear to be more effective than those working on the serotonin system alone.

Personality in patients with migraine evaluated with the "Temperament and Character Inventory"

“…In keeping with our results, Pud et al [47] showed a correlation between high scores of HA with pain threshold (latency to pain onset), pain magnitude (VAS), and pain tolerance (time to withdrawal) using the cold pressor test in healthy patients. The involvement of serotonin in chronic pain [48][49][50][51] is consistent with the proposed physiopathological mechanisms of HA in the central nervous system [23].…”

Effects of repeated milnacipran and fluvoxamine treatment on mechanical allodynia in a mouse paclitaxel-induced neuropathic pain model

“…Milnacipran shows equivalent inhibitory activity at both NA and 5-HT neuronal reuptake systems (18). Obata et al reported the involvement of both NA and 5-HT in the antiallodynic effect of milnacipran in a rat neuropathic pain model (20).…”

“…Moreover, fluvoxamine showed an antiallodynic effect in a streptozotocin-induced diabetic neuropathy model (9). Similar to the research on SSRIs, the analgesic effects of SNRIs have also been examined using a variety of animal models of pain (18). One typical SNRI, milnacipran, has been shown to be efficacious for the prevention and/or reversal of pain in several preclinical models of acute and chronic pain in rodents.…”

Regulation of Pain in Fibromyalgia by Selective Serotonin and Serotonin Norepinephrine Reuptake Inhibition

“…In that regard, imipramine and milnacipran were shown to yield significant anti-nociceptive effects in a model of chronic pain in rodents induced by formalin injection [39] and in the same study, venlaxafine, a dual reuptake inhibitor, prevented the development of a form of neuropathic pain induced by chronic constriction injury of the sciatic nerve. Of note, milnacipran and duloxetine decreased pain sensitivity whereas, the SSRI, fluoxetine did not.…”