Arch Neurosci. 2015 April; 2(2): e18214. DOI: 10.5812/archneurosci.18214 Published online 2015 April 1. Review Article Nerve Injury-Induced Plasticity in the Nociceptive Pathways Zahra Bahari 1 ; Seyed Shahabeddin Sadr 2,* ; Gholam Hossein Meftahi 3 ; Maedeh Ghasemi 4 ; Homa Manaheji 1 ; Alireza Mohammadi 3 ; Nasrin Mehranfard 2 1 Department of Neurophysiology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran 2 Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IR Iran 3 Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran 4 Department of Physiology, Isfahan University of Medical Sciences, Isfahan, IR Iran *Corresponding author: Seyed Shahabeddin Sadr, Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98- 2166521520, Fax: +98-2166521520, E-mail: sadr@tums.ac.ir Received: February 23, 2014; Revised: June 8, 2014; Accepted: June 30, 2014 Context: Neuropathic pain is a common and disabling complication. To develop a better treatment of the neuropathic pain, a comprehensive understanding is essential. In this paper, we review pathophysiological principles of neuropathic pain, focusing on synaptic plasticity and long-term potentiation (LTP) in the nociceptive circuits. Finally, the role of glial cells on the synaptic plasticity in neuropathic pain is discussed. Evidence Acquisition: We searched the Cochrane and PubMed databases using the following terms: neuropathic pain, dorsal horn, LTP, synaptic plasticity, nociceptive circuits, glial cells, nerve injury, allodynia, hyperalgesia, nociceptive neurons, and rat. All of searches were limited to the animal studies in English articles. Full-text copies were obtained when the studies had possible relevance. Results: Analysis of our research showed that nerve injury-induced LTP decreased pain threshold and increased pain hypersensitivity to sub-threshold stimuli. In addition, cross talk between dorsal horn neurons and glial cells are pivotal for the induction of spinal synaptic plasticity and LTP. Conclusions: It seems that LTP in the spinal nociceptive pathways constitutes cellular mechanisms that explains how acute pain may become chronic. Keywords:- Copyright © 2015, Tehran University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCom- mercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial us- ages, provided the original work is properly cited. 1. Context Neuropathic pain is a common and severely disabling complication that impairs quality of life. The treatment of neuropathic pain is problematic because it is very complex, and the underlying mechanisms are not clearly understood (1). In recent years, attention was focused on synaptic plasticity in the dorsal horn as an important mechanism for neuropathic pain. One important type of the synaptic plasticity is LTP in the spinal neural system (2). Therefore, targeting maladaptive neuronal plasticity and LTP in the spinal pathways is an important way for the treatment of neuropathic pain. Moreover, recently it has been reported that glial cells are critical for the de- velopment and maintenance of synaptic plasticity (3). The aim of this review is to investigate recent progress in the neuropathic pain pathophysiology. We focus on the synaptic plasticity and LTP in nociceptive circuits. Finally, the cross talk between neuronal and glial cells in neuro- pathic pain is discussed. 2. Evidence Acquisition We searched the Cochrane and PubMed database without date limitation, using the following terms: neuropathic pain, dorsal horn, LTP, synaptic plasticity, nociceptive circuits, glial cells, nerve injury, allodynia, hy- peralgesia, nociceptive neurons, and rat. Following this search, we conducted a backward search by examining reference lists of all obtained articles. The searches were limited to the animals in English language. We checked all titles and abstracts. Full-text copies were obtained when the studies had possible relevance. 3. Results 3.1. Neuropathic Pain Clinical pain can arise from damage to the nervous sys- tem (neuropathic pain), inflammation, or tissue injury (inflammatory pain). Etiology of neuropathic pain is dif- ferent and includes nerve injury (e.g. amputation, spinal cord injury) or diseases that affect peripheral nerve func- tion (e.g. metabolic disorders, viral infection and cancer). The most distinctive signs of neuropathic pain are hy- peralgesia (an exaggerated response to painful stimuli), allodynia (the presence of pain in response to normally non-painful tactile stimuli) and spontaneous pain (stim-