Tramadol has a Better Potency Ratio Relative to Morphine in Neuropathic than in

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Drugs R D. 2007;8(1):51-7.

Tramadol has a Better Potency Ratio Relative to Morphine in

Neuropathic than in Nociceptive Pain Models.

Christoph T, Kogel B, Strassburger W, Schug SA.

Biomedical Research, Grunenthal GmbH, Aachen, Germany.

BACKGROUND AND OBJECTIVE: Treatment of neuropathic pain remains a

challenge and the role of various analgesics in this setting is

still debated. The effects of tramadol, an atypically acting

analgesic with a combined opioid and monoaminergic mechanism of

action, and morphine, a prototypical opioid, were tested in rat

models of neuropathic and nociceptive pain.

METHODS: Cold allodynia and mechanical hypersensitivity, symptoms of

neuropathic pain, were studied in rat models of mononeuropathic

pain. Cold allodynia was analyzed in the chronic constriction injury

(CCI) model and mechanical hypersensitivity was analyzed in the

spinal nerve ligation (SNL) model. Heat-induced rat tail-flick

latencies were determined as measure for nociceptive pain.

RESULTS: Cold allodynia and mechanical hypersensitivity were

strongly attenuated with similar absolute potency after intravenous

administration of tramadol and morphine. The doses of drug that were

calculated to result in 50% pain inhibition (ED(50)) for tramadol

and morphine were 2.1 and 0.9 mg/kg, respectively, in CCI rats and

4.3 and 3.7 mg/kg, respectively, in SNL rats. In the tail-flick

assay of acute nociception, the potency of the two drugs differed

markedly, as seen by ED(50) values of 5.5 and 0.7 mg/kg

intravenously for tramadol and morphine, respectively. Accordingly,

the analgesic potency ratio (ED(50) tramadol/ED(50) morphine) of

both compounds differed in neuropathic (potency ratio 2.3 in CCI and

1.2 in SNL) and nociceptive pain models (potency ratio 7.8),

suggesting a relative increase in potency of tramadol in neuropathic

pain compared with nociceptive pain.

CONCLUSION: The results of this study are consistent with clinical

data supporting the efficacy of opioids in neuropathic pain

conditions, and furthermore suggest an additional contribution of

the monoaminergic mechanism of tramadol in the treatment of

neuropathic pain states.