Tramadol produces outward currents by activating mu-opioid receptors in adult rat substantia gelatinosa neurones.
1. 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. 2. 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. 3. M1 current correlated in amplitude with current produced by mu-opioid receptor agonist DAMGO in the same neurone, and largely reduced in amplitude in the presence of mu-opioid receptor antagonist CTAP but not alpha2-adrenoceptor antagonist yohimbine. In a neurone where M1 had no effect on holding currents, noradrenaline produced an outward current at -70 mV. 4. The amplitude of the M1 response, relative to that of the DAMGO response, exhibited an EC(50) value of 300 microM. 5. We conclude that M1 produces a persistent hyperpolarization by activating mu-opioid receptors in adult rat SG neurones. This could contribute to at least a part of pain alleviation produced by tramadol.
Koga
Akiko
A
Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Fujita
Tsugumi
T
Totoki
Tadahide
T
Kumamoto
Eiichi
E
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D013376:Substantia Gelatinosa / Q000166:cytology / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D014147:Tramadol / Q000494:pharmacology*
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D013565:Sympatholytics; D013566:Sympathomimetics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D014147:Tramadol