In neuropathic pain treatment a combined use of tramadol and antidepressants constitutes a common clinical practice. Therefore assessment of the nature of interaction between tramadol and doxepin or venlafaxine was undertaken. Research was conducted on Wistar rats. Neuropathic pain model described by Bennett (Chronic Constriction Injury) was applied. 15 days after the surgical procedure pathologic symptoms characteristic for neuropathic pain were assessed, that is: mechanical allodynia (vonFrey test) and thermal hyperalgesia (paw withdrawal latency test). Observations were carried out for 120 minutes after intraperitoneal drug administration. Nature of interaction was estimated using isobolographic analysis and indices of interaction were calculated. The obtained results confirmed effectiveness of all drugs in reduction of thermal hyperalgesia and mechanical allodynia, however doxepin was more effective than venlafaxine. Combined administration of tramadol and doxepin demonstrated synergetic action in reducing thermal hyperalgesia and additive action in reducing mechanical allodynia. Interaction between tramadol and venlafaxine was additive in both tests. Additionally, involvement of opioid mechanism was detected (by blocking of opioid receptors with naloxone) for tramadol and venlafaxine but not for doxepin. In conclusion, the experiments confirmed hypothesis that the nature of interaction between tramadol and doxepin (tricyclic antidepressive drug) is synergetic, what provides a valuable information referring to clinical practice, rationalizing administration of such drug combination.