Background and purpose: Although tramadol is known to exhibit a local anaesthetic effect, how tramadol exerts this effect is not understood fully. Experimental approach: The effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) were examined by applying the air-gap method to frog sciatic nerves, and the results were compared with those of other local anaesthetics, lidocaine and ropivacaine. Key results: Tramadol reduced the peak amplitude of the CAP in a dose-dependent manner (IC 50 ¼ 2.3 mM). On the other hand, M1 (1-2 mM), which exhibits a higher affinity for m-opioid receptors than tramadol, did not affect CAPs. These effects of tramadol were resistant to the non-selective opioid receptor antagonist naloxone and the m-opioid receptor agonist, DAMGO, did not affect CAPs. This tramadol action was not affected by a combination of the noradrenaline uptake inhibitor, desipramine, and the 5-hydroxytryptamine uptake inhibitor, fluoxetine. Lidocaine and ropivacaine also concentrationdependently reduced CAP peak amplitudes with IC 50 values of 0.74 and 0.34 mM, respectively. Conclusions and implications: These results indicate that tramadol reduces the peak amplitude of CAP in peripheral nerve fibres with a potency which is less than those of lidocaine and ropivacaine, whereas M1 has much less effect on CAPs. This action of tramadol was not produced by activation of m-opioid receptors nor by inhibition of noradrenaline and 5-hydroxytryptamine uptake. It is suggested that the methyl group present in tramadol but not in M1 may play an important role in producing nerve conduction block.

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We consider a two-band spinless model describing an excitonic insulator (EI) on the two-dimensional square lattice with anisotropic hopping parameters and electron-phonon (el-ph) coupling, inspired by the EI candidate Ta 2 NiSe 5. We systematically study the nature of the collective excitations in the ordered phase which originates from the interband Coulomb interaction and the el-ph coupling. When the ordered phase is stabilized only by the Coulomb interaction (pure EI phase), its collective response exhibits a massless phase mode in addition to the amplitude mode. We show that in the BEC regime, the signal of the amplitude mode becomes less prominent and that the anisotropy in the phase-mode velocities is reduced. Through coupling to the lattice, the phase mode acquires a mass and the signal of the amplitude mode becomes less prominent. Importantly, the character of the softening mode at the boundary between the normal semiconductor phase and the ordered phase depends on the parameters. In particular, we point out that even for el-ph coupling smaller than the Coulomb interaction, the mode that softens to zero at the boundary can have a phonon character. We also discuss how the collective modes can be observed in the optical conductivity. Furthermore, we study the effects of nonlocal interactions on the collective modes and show the possibility of realizing a coexistence of an in-gap mode and an above-gap mode split off from the single-amplitude mode in the system with local interactions only.

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