ABSTRACT
Neuropathic pain is a chronic debilitating condition caused by injury or disease of the nerves of the somatosensory system. Although several therapeutic approaches are recommended, none has emerged as an optimal treatment leaving a need for developing more effective therapies. Given the small number of approved drugs and their limited clinical efficacy, combining drugs with different mechanisms of action is frequently used to yield greater efficacy. We demonstrate that the combination of trazodone, a multifunctional drug for the treatment of major depressive disorders, and gabapentin, a GABA analogue approved for neuropathic pain relief, results in a synergistic antinociceptive effect in the mice writhing test. To explore the potential relevance of this finding in chronic neuropathic pain, pharmacodynamic interactions between low doses of trazodone (0.3 mg/kg) and gabapentin (3 mg/kg) were evaluated in the chronic constriction injury (CCI) rat model, measuring the effects of the two drugs both on evoked and spontaneous nociception and on general well being components. Two innate behaviors, burrowing and nest building, were used to assess these aspects. Besides exerting a significant antinociceptive effect on hyperalgesia and on spontaneous pain, combined inactive doses of trazodone and gabapentin restored in CCI rats innate behaviors that are strongly reduced or even abolished during persistent nociception, suggesting that the combination may have an impact also on pain components different from somatosensory perception. Our results support the development of a trazodone and gabapentin low doses combination product for optimal multimodal analgesia treatment.
Subject(s)
Analgesics/therapeutic use , Anti-Anxiety Agents/therapeutic use , Gabapentin/therapeutic use , Neuralgia/drug therapy , Trazodone/therapeutic use , Analgesics/pharmacology , Animals , Anti-Anxiety Agents/pharmacology , Depressive Disorder, Major/drug therapy , Disease Models, Animal , Drug Synergism , Gabapentin/pharmacology , Male , Mice , Nociception/drug effects , Trazodone/pharmacologyABSTRACT
A lattice calculation is presented for the electrical conductivity σ of the QCD plasma with 2+1 dynamical flavors at nonzero temperature. We employ the conserved lattice current on anisotropic lattices using a tadpole-improved clover action and study the behavior of the conductivity over a wide range of temperatures, both below and above the deconfining transition. The conductivity is extracted from a spectral-function analysis using the maximal entropy method, and a discussion of its systematics is provided. We find an increase of σ/T across the transition.
