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Uses

Tramadol is used to treat moderate and severe pain and most types of neuralgia, including trigeminal neuralgia.^{[citation needed]} It has been suggested that tramadol could be effective for alleviating symptoms of depression and anxiety because of its action on GABAergic, noradrenergic and specifically serotonergic systems. However, health professionals have not yet endorsed its use on a large scale for disorders such as this.^[4][5]

[edit] Off-label and investigational uses

• diabetic neuropathy^[6][7]
• postherpetic neuralgia^[8][9]
• fibromyalgia^[10]
• restless legs syndrome^[11]
• opiate withdrawal management^[12][13]
• migraine headache^[14]
• obsessive-compulsive disorder^[15]
• premature ejaculation^[16]

[edit] Veterinary

Tramadol is used to treat post-operative and/or chronic (e.g. cancer-related) pain in dogs and cats.[1]

[edit] Mechanism of action

The mode of action of tramadol has yet to be fully understood, but it is believed to work through modulation of the GABAergic, noradrenergic and serotonergic systems, in addition to its mild agonism of the μ-opioid receptor. The contribution of non-opioid activity is demonstrated by the analgesic effects of tramadol not being fully antagonised by the μ-opioid receptor antagonist naloxone.

Tramadol is marketed as a racemic mixture with a weak affinity for the μ-opioid receptor (approximately 1/6th that of morphine). The (+)-enantiomer is approximately four times more potent than the (-)-enantiomer in terms of μ-opioid receptor affinity and 5-HT reuptake, whereas the (-)-enantiomer is responsible for noradrenaline reuptake effects (Shipton, 2000). These actions appear to produce a synergistic analgesic effect, with (+)-tramadol exhibiting 10-fold higher analgesic activity than (-)-tramadol (Goeringer et al., 1997).

The serotonergic modulating properties of tramadol mean that it has the potential to interact with other serotonergic agents. There is an increased risk of serotonin syndrome when tramadol is taken in combination with serotonin reuptake inhibitors (e.g. SSRIs), since these agents not only potentiate the effect of 5-HT but also inhibit tramadol metabolism. Tramadol is also thought to have some NMDA-type antagonist effects which has given it a potential application in neuropathic pain states.