Tramadol produces outward currents by activating μ-opioid receptors in adult rat substantia gelatinosa neurones

Abstract

An action of a tramadol metabolite, mono-O-dimethyl-tramadol (M1), on substantia gelatinosa (SG) neurones in adult rat spinal cord slices was examined by using the whole-cell patch-clamp technique. In 41% of the neurones examined, superfusing M1 produced an outward current at -70 mV; this response reversed at a potential close to the equilibrium potential for K +. M1 current hardly declined and persisted for > 30 min after its washout. M1 current correlated in amplitude with current produced by μ-opioid receptor agonist DAMGO in the same neurone, and largely reduced in amplitude in the presence of μ-opioid receptor antagonist CTAP but not α2-adrenoceptor antagonist yohimbine. In a neurone where M1 had no effect on holding currents, noradrenaline produced an outward current at -70 mV. The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC 50 value of 300 μM. We conclude that M1 produces a persistent hyperpolarization by activating μ-opioid receptors in adult rat SG neurones. This could contribute to at least a part of pain alleviation produced by tramadol. © 2005 Nature Publishing Group. All rights reserved.