Mechanism of development and maintenance of chronic neuropathic pain is extremely complex and, among other things, includes a number of peripheral and central changes in the number and function of various molecules such as N type Ca2+ channel, TRPV1 vanilloid receptor, tetrodotoxin (TTX)-sensitive Na+ channels and the ASIC ionic channels, as well as opioid mu, delta and kappa receptors. Numerous research has shown the significant role the endogenous opioid system has in processes of transmission and modulation of painful stimuli. Of the three main opioid peptide groups, the best evidence for their involvement in the regulation of nociceptive processes on the spinal level has been found for enkephalins. Albeit primarily inhibitory, the role of the opioid system in chronic pain can be substantially altered. It is precisely the role that the opioid system has in neuropathic pain of complex pathophysiology and chronic in its character that is primarily the subject of research, and the results of fundamental research sometimes show contradictory conclusions. In this work enkephalin immunoreactivity was measured by immunohistochemical methods in tissue samples of the dorsal horn of the spinal cord of control animals and animals with neuropathic pain induced by partial transection of a peripheral nerve. We have shown that after a unilateral nerve injury enkephalin immunoreactivity in the dorsal horn enhances on both sides. This brings us to the conclusion that despite the increased enkephalin concentration, in conditions of chronic hypersensitivity decreases the number of μ and probably δ opioid receptors through which enkephalins exercise their physiological effects. In order to gather further evidence on the above hypothesis, further research is needed that will contribute to a better understanding of the complex phenomenon neuropathic pain, and ultimately result in more effective treatment of patients.