Article date: July 2005
By: Akiko Koga, Tsugumi Fujita, Tadahide Totoki, Eiichi Kumamoto in Volume 145, Issue 5, pages 602-607
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 EC50 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.
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 EC50 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.
British Journal of Pharmacology (2005) 145, 602–607. doi:10.1038/sj.bjp.0706225
DOI: 10.1038/sj.bjp.0706225
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