Antidepressants in the Treatment of Neuropathic Pain

Abstract

Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4-5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class -may among the antidepressants -favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain.Neuropathic pain is pain caused by a lesion or dysfunction in the nervous system with the primary lesion or dysfunction affecting either the peripheral or central nervous system. Prominent examples of peripheral neuropathic pain conditions are painful diabetic neuropathy, post-herpetic neuralgia and post-surgical neuropathic pain and the most common central neuropathic pain conditions are poststroke pain, pain in multiple sclerosis and spinal cord injury pain. Neuropathic pain is also present in some other patient groups, e.g. cancer patients. Therefore, the scope of neuropathic pain is broader than the classical peripheral and central neuropathic pain conditions. The neuropathic pain conditions are most often chronic in nature and represent a real challenge in clinical practice both due to their fre...

The carbon monoxide donor, CORM-2, is an antagonist of ATP-gated, human P2X4 receptors

“…P2X4 receptors are relatively insensitive to broad-spectrum P2X antagonists, suramin and PPADS [3,14], and although a specific P2X4 antagonist has been reported [39], data regarding its effectiveness and specificity have not yet been published. Tri-cyclic antidepressant drugs such as paroxetine, fluoxetine, desipramine and amitriptyline have been prescribed for many years for the treatment of neuropathic pain [40] and were recently shown to inhibit P2X4 receptor function [15], a mechanism which may contribute to their analgesic properties. However, recent studies by Toulme et al [17] have shown that, with the exception of paroxetine which has some direct effects on P2X4 currents, these drugs act by disrupting lysosomal function and the trafficking of P2X4 receptors to the plasma membrane and are, therefore, not true P2X4 antagonists.…”

Postherpetic Neuralgia: From Preclinical Models to the Clinic

“…43 Additionally, the tricyclic antidepressant amitriptyline and the cannabinoid agonist WIN 55,212-2 were found to reverse VZV-induced mechanical allodynia, and both have been found effective in clinical trials for either PHN or other neuropathic conditions. 43,80,81 In summary, these preclinical investigations have revealed similarities between a rodent model of chronic pain induced by VZV infection and models of chronic pain from peripheral nerve injury, although more investigation is needed to reveal whether there are physiological changes specific to the VZV model.…”

Dynorphin a Analogs for the Treatment of Chronic Neuropathic Pain

“…Anticonvulsants such as pregablin and gabapentin are often prescribed and are effective for patients with postherpetic neuralgia, fibromyalgia and diabetic peripheral neuropathy [5]. For over 40 years, antidepressants such as tricycles, selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors have been used for the treatment of neuropathic pain and show efficacy for some patients [6]. Steroids are generally used as an adjunct therapy with opioids and are beneficial to patients with metastatic bone pain, visceral pain and neuropathic pain [7].…”