An Investigation of Monoamine Receptors Involved in Antinociceptive Effects of Antidepressants

Abstract

Formalin tests of rats treated with antidepressants and antagonists of monoamine receptors indicate that alpha(1) adrenoceptors, serotonin (5-HT)(2) receptors, and 5-HT(3) receptors are involved in antidepressant-induced antinociception, suggesting functional interactions between noradrenergic and serotonergic neurons as mechanisms of antidepressant-induced antinociception.

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

“…Milnacipran and fluvoxamine are used for the treatment of acute and neuropathic pain as a supplementary analgesic (16,21). There have been several reports indicating that milnacipran and fluvoxamine have significant antinociceptive effects against nociceptive and inflammatory pain (20,22,27,28,30). Furthermore, milnacipran was more effective than SSRIs such as fluvoxamine, paroxetine, and citalopram in attenuating persistent pain (30) and neuropathic pain (9), and more effective than amitriptyline (TCAs) in attenuating cold allodynia (4°C cold plate stimuli) (1).…”

“…The antinociceptive effects of SSRIs have been reported in a number of animal experiments (12,13,25). One typical SSRI, fluvoxamine, attenuated licking behavior in the late phase of the formalin test (22,30) and also in the hot-plate test (27), but it failed to attenuate mechanical allodynia in a neuropathic pain model (chronic constriction injury model) (9). Moreover, fluvoxamine showed an antiallodynic effect in a streptozotocin-induced diabetic neuropathy model (9).…”

“…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. Yokogawa et al demonstrated that milnacipran significantly attenuated late phase paw licking behavior in the formalin test (30) and also reversed mechanical allodynia in the chronic constriction injury model or spinal nerve ligation model of neuropathic pain (9,28). In addition, milnacipran had an antiallodynic effect on the streptozotocin-induced diabetic neuropathy model (9) and potentiated the antihyperalgesic effect of tramadol (opioid analgesic) (21).…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…In preclinical models, naloxone, an opioid antagonist, decreased the analgesic effect of intraspinal serotonin and vice-versa with serotonin antagonists blocking the analgesic effects of morphine near the spinal cord (McHugh and McHugh, 2000). In rats, antidepressants and antagonists of monoamine receptors treatment decreased formalin-evoked nociceptive behaviour, indicating functional interactions between noradrenergic and serotonergic neurons as mechanisms of antidepressant-induced pain-control (Yokogawa et al, 2002).…”

Antidepressant Drugs and Pain

“…For example, the inhibition of tyrosine hydroxylase (an essential enzyme for noradrenaline synthesis) or tryptophan hydroxylase (an essential enzyme for serotonin synthesis) antagonizes the analgesic effect of antidepressants in a wide range of experimental models (Valverde et al, 1994). Monoamines act on multiple receptor subtypes in the nervous system, some of which mediate the analgesic effect of antidepressants, such as -adrenoceptors (Ghelardini et al, 2000;Yokogawa et al, 2002) and -adrenoceptors (Mico et al, 2006b), 5-HT 1A , 5-HT 2 and 5-HT 3 serotonin receptors (Bonnefont et al, 2005;Yokogawa et al, 2002), and D2 dopamine receptors (Gilbert & Franklin, 2001). …”