Mechanism-Based Treatment in Chronic Neuropathic Pain: The Role of Antidepressants

Abstract

Antidepressant drugs have been widely used for many years to treat neuropathic pain, despite the rationale for their use was still unclear. We review recent insights into their mechanism of action, focusing on central and peripheral analgesic actions. Beside the traditional monoaminergic hypothesis, other pharmacological actions have been studied: antidepressants interfere with the opioid system, interact with the NMDA receptors, and inhibit ion channel activity. Firm evidence from randomised controlled trials demonstrated that TCAs are the most effective drugs for treatment of different neuropathic pain conditions. They exhibit the lowest number needed to treat compare with all other drugs investigated. SSRIs failed to provide an adequate analgesia, due to their high selectivity. SSRIs are clearly less effective than TCAs (NNT: 6.7 vs 2.4) supporting the hypothesis that a balanced inhibition of noradrenaline and serotonin reuptake is more effective in relieving pain. On the basis of initial results Venlafaxine seems to be the most promising of the newer antidepressants as analgesic. Newer antidepressants show a better side effects profile, but further investigation are warranted to clarify their potential role in management of pain. Neuropathic pain remains a challenging condition to treat, as all currently available drugs fail to achieve adequate pain relief in a significant proportion of patients. TCAs should be currently considered the first choice in treatment of neuropathic pain and the gold standard against which to compare other potential new treatments.

Usefulness of Antidepressants for Improving the Neuropathic Pain-Like State and Pain-Induced Anxiety through Actions at Different Brain Sites

“…Antidepressant drugs are efficacious and have been widely used in the management of chronic pain conditions (Max et al, 1987;Richeimer et al, 1997). Firm evidence has shown that tricyclic antidepressants (TCAs) should be considered the gold standard treatment for neuropathic pain (Coluzzi and Mattia, 2005;Sindrup et al, 2005). It has also been reported that the analgesic effect of antidepressants is independent of their antidepressive action, and occurs at lower doses and with a faster onset of action in a clinical situation (Pilowsky et al, 1982;Onghena and Van Hondenhobe, 1992;Richeimer et al, 1997).…”

Emotional distress and pain tolerance in obsessive-compulsive disorder

“…However, there were no group differences in threshold or mean pain rating, suggesting that all subjects perceived the pain to an equal extent. The absence of difference implies that medications did not affect our results even though some studies show that SSRIs and other antidepressants can increase pain tolerance (Coluzzi & Mattia, 2005).…”

Anti-hyperalgesic effect of paracetamol in rat model of thermal hyperalgesia: implications for the treatment of neuropathic pain

“…Other possible analgesic mechanisms suggested for AMT include increase in the release of endogenous opioids, blockade of N-methyl-Daspartate (NMDA) receptors, blockade of Na + and Ntype Ca + channels and opening of K + channels. 19,20 Several mechanisms of anti-nociceptive activity of PCM have been proposed by different researchers but the exact mechanism of action still remains to be elucidated. First well known and widely accepted mechanism includes inhibition of several isoforms of cyclooxygenase (COX) enzyme.…”