Neuropathic pain modeling: Focus on synaptic and ion channel mechanisms

Animal models of pain consist of modeling a pain-like state and measuring the consequent behavior. The first animal models of neuropathic pain (NP) were developed in rodents with a total lesion of the sciatic nerve. Later, other models targeting central or peripheral branches of nerves were developed to identify novel mechanisms that contribute to persistent pain conditions in NP. Objective assessment of pain in these different animal models represents a significant challenge for pre-clinical research. Multiple behavioral approaches are used to investigate and to validate pain phenotypes including withdrawal reflex to evoked stimuli, vocalizations, spontaneous pain, but also emotional and affective behaviors. Furthermore, animal models were very useful in investigating the mechanisms of NP. This review will focus on a detailed description of rodent models of NP and provide an overview of the assessment of the sensory and emotional components of pain. A detailed inventory will be made to examine spinal mechanisms involved in NP-induced hyperexcitability and underlying the current pharmacological approaches used in clinics with the possibility to present new avenues for future treatment. The success of pre-clinical studies in this area of research depends on the choice of the relevant model and the appropriate test based on the objectives of the study.