Current drug treatments for neuropathic pain include antiinflammatory drugs, antidepressants and opioids, even if effectiveness of opioids in the treatment of neuropathic pain remains controversial. Overall, no pharmacotherapy has so far emerged as an effective treatment for neuropathic pain.
Aim of this study was to verify the synergism of the combination of inactive doses of trazodone, a multifunctional drug used for the treatment of major depressive disorders, and gabapentin, a GABA analogue currently used to relieve neuropathic pain, in the chronic constriction injury model (CCI), a widely used animal model of neuropathic pain.
CCI was induced in SD rats by loosely constrictive ligatures around the sciatic nerve trunk at mid-thigh level. 
Mechanical hyperalgesia and spontaneous pain (weight bearing, burrowing performance, nest construction) were measured following trazodone (0.3mg/kg) and gabapentin (3mg/kg) in single or combined administration. All procedures conformed to the guidelines of the European Community’s Council for Animal Experiments.
When animals received two low and ineffective doses of trazodone and gabapentin in combination, a marked and significant antihyperalgesic effect was observed. CCI-induced neuropathic pain also reduced weight bearing of the injured limb, burrowing activity and nest performance. The combination normalized weight bearing deficit and restored the burrowing performance as well as the ability of nestlet shredding.
Our data suggest that trazodone-gabapentin low doses combination not only is effective in inducing a synergistic analgesic activity, which can be of interest for optimal multimodal clinical analgesia, but it also exerts a positive effect on the emotional and cognitive components of pain.

ANALGESIC EFFECT OF THE TRAZODONE-GABAPENTIN COMBINATION IN THE CHRONIC CONSTRICTION INJURY RAT MODEL