The purpose of this study was to shed light on the neurochemical modulatory mechanisms of the noxious spinal inhibitory cutaneous silent period (CSP). We study the effects of 100mg of oral tramadol in 11 healthy volunteers. Tramadol has low affinity for opioid receptors and has the ability to inhibit serotonin and noradrenaline reuptake. We elicited CSPs in the first dorsal interosseus muscle and noxious withdrawal flexor reflexes (NWR) in the right biceps femoris muscle before, 30min and each hour up to the 6th after tramadol. Subjective pain sensation was checked on an 11-point numerical scale. Tramadol increased duration of CSP, and reduced the NWR area under the curve maximally 2h after tramadol and paralleled the reduction of subjective pain perception. We suggest that the monoaminergic action of tramadol reinforces the activity of spinal inhibitory interneurons on α-motoneurons for the hand muscles.