Venlafaxine and Neuropathic Pain

Abstract

The possible mechanisms involved in the antinociceptive effect of venlafaxine (VFX), a selective serotonin and noradrenaline reuptake inhibitor, after a single administration and chronic treatment were investigated in a diabetic neuropathic pain (DNP) model. VFX produced a significant antihyperalgesic effect after a single and repeated administration. This effect was reversed by pretreatment with yohimbine (a relatively selective α₂-adrenergic antagonist) and p-chloroamphetamine (a neurotoxin which destroys serotonergic neurons). Conversely, naloxone (a nonselective opioid antagonist) did not reverse the effect of VFX in a DNP model. It is concluded that both noradrenergic and serotonergic mechanisms participate in the antinociceptive effect of VFX in the DNP model. However, the noradrenergic mechanism probably plays a more important role.

Impaired Noradrenaline Homeostasis in Rats with Painful Diabetic Neuropathy as a Target of Duloxetine Analgesia

“…The present results support the finding that the analgesic effect of DLX is mediated by its effect on NA transport because the suppression of the DLX effect by DSP-4 pretreatment was clearly observed when DSP-4 treatment was combined with injection of an SSRI (fluoxetine) [28] (see Results). This conclusion that the presence of serotoninergic fibers is not sufficient to produce the anti-nociceptive effect of DLX in PDN is also supported by a recent finding in STZ-treated rats, that the anti-nociceptive effect of another SNRI, venlafaxine, was completely abolished by yohimbine pre-treatment but was only partially inhibited by pretreatment with p-choloroamphetamine, an agent that degenerates serotoninergic fibers [16]. However, partial but significant reduction of analgesic effect of DLX and another SNRI, milnacipran, by 5-HT receptor antagonists has been described in STZ-treated PDN [12] and postoperative pain [37] models of rats.…”

“…This pain relief effect is not unique to DLX, and it is possessed by other SNRIs, which also improve the exaggerated pain in diabetic patients [14] and animal models [15,16]. SNRIs, including DLX, are recommended to be one of the first-line treatments for patients with PDN [5,17].…”

Diabetic neuropathic pain: Physiopathology and treatment

“…The NNT for duloxetine varies from 1.3 to 5.1 in DNP patients [146,147] , which experience more frequently nausea, somnolence and dizziness as side effects [146] . Venlafaxine is also a selective serotonin and nora drenaline reuptake inhibitor, that predominantly inhibits serotonin reuptake at low doses and noradrenaline at higher doses [148] . Venlafaxine was also shown to be effective in reducing pain intensity in diabetic neuropathic patients [149] , with an NNT between 2.2 and 5.1 and a number needed to harm (NNH) of 9.6, to minor adverse effects, and of 16.2, for major adverse effects [150] .…”

Efficacy of Venlafaxine in Neuropathic Pain: A Narrative Review of Optimized Treatment

“…In animal models, VLX acts via both the noradrenergic and serotoninergic systems through increases in serotonin and norepinephrine levels, leading to the relief of neuropathic pain through an intensification of the inhibitory descending pathway. 22,23 The noradrenergic system seems to be the dominant system in this effect, 24 as confirmed by studies of selective noradrenalin reuptake inhibitors. 25,26 VLX also reduces spinal hyperexcitability through a blockade of central 5-HT 1A receptors.…”