Beneficial effects of fish oil enriched in omega-3 fatty acids on the development and maintenance of neuropathic pain Santiago R. Unda a , Emilce A. Villegas b , Mar  ıa Eugenia Toledo b , Gabriela Asis Onell c and Carlos H. Laino b a Weill Cornell Medicine, Department of Neurological Surgery, Molecular Neurosurgery Laboratory, New York, NY, USA , b Biotechnology Institute, Research and Technological Innovation Center (CENIIT)-National University of La Rioja, La Rioja and c Medical Sciences Faculty, National University of C ordoba, C ordoba, Argentina Keywords mechanical allodynia; neuropathic pain; omega-3 fatty acids; thermal hyperalgesia Correspondence Carlos H. Laino, Biotechnology Institute, Research and Technological Innovation Center (CENIIT)-National University of La Rioja, Av. Luis M de la Fuente SN, 5300 La Rioja, Argentina. E-mail: carloslaino25@gmail.com Received August 5, 2019 Accepted November 23, 2019 doi: 10.1111/jphp.13213 Abstract Objective The aim of this work was to assess the preventive effect of an eicos- apentaenoic acid/docosahexaenoic acid-concentrate fish oil on neuropathic pain development and regenerative features of sciatic nerve in rats. Methods In the present study, rats with chronic constriction injury (CCI) of the sciatic nerve and sham-operated ones received fish oil enriched in omega-3 fatty acids (0.36 or 0.72 g/kg per day, oral) or saline solution for 21 days, with thermal hyperalgesia and mechanical allodynia being assessed before and 3, 7, 14 and 21 days after injury. Key findings Fish oil enriched in omega-3 fatty acids (0.72 g/kg) reversed ther- mal hyperalgesia and significantly reduced mechanical allodynia. In addition, x-3 treatment (0.72 g/kg) promoted the recovery of the Sciatic Functional Index as well as restored axonal density and morphology, without the formation of neu- roma in the injured sciatic nerves after 21 days. Conclusion We conclude that the fish oil enriched in omega-3 fatty acids administration relieves thermal hyperalgesia and mechanical allodynia effectively and also enhances the recovery process in rats with CCI of the sciatic nerve. These findings might contribute to new therapeutic approaches including omega-3 fatty acids in neuropathic pain treatment. Introduction According to the International Association for the Study of Pain (IASP), neuropathic pain is defined as ‘pain caused by a lesion or disease of the somatosensory nervous system’. [1] It occurs in various disorders of the nervous system, but as the signs and symptoms may or may not be related to the injured site, this makes the task of diagnosing and treating the pain difficult in medical practice. [2,3] Neuropathic pain may be associated with traumatic injury to the spinal cord and brain, or due to lumbar disc syn- drome, [4] the entrapment of the ulnar nerve (ulnar tunnel syndrome) or phantom limb pain. [5] It may also be present in various diseases, including diabetes, [6] cancer, [7] herpes zoster infection [8] and human immunodeficiency virus infection. [9] This painful condition may result from an injury or dis- ease of the nervous system (which may be both peripheral and central), so that the nociceptive system behaves abnor- mally with there being a total lack of a causal relationship between tissue injury and pain. This is characterized by pain of a spontaneous type and a painful hypersensitivity that can be differentiated between allodynia and hyperalge- sia. [2,10,11] which affect up to 50% of patients with neuro- pathic pain, although allodynia and hyperalgesia epidemiology are difficult to assess due to the subjective nature of these symptoms. [12] Neuropathic pain is an important clinical problem, since it is a debilitating condition that seriously compromises the quality of life. It is a state of chronic pathological pain, a leader worldwide, as it endures beyond the resolution of the source of pain and can profoundly affect the quality of life. [13] In addition, neuropathic pain and syndromes asso- ciated with an important pharmacological characteristic, as it responded poorly, or only to available therapies, which often have specific adverse effects. [14,15] Consequently, there is still a need to explore new therapeutic strategies to iden- tify effective and safer drugs with minimal, or at least reduced adverse effects. [16] © 2019 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 72 (2020), pp. 437–447 437 Research Paper Downloaded from https://academic.oup.com/jpp/article/72/3/437/6122102 by guest on 27 November 2022