Animal Models of Neuropathic Pain Due to Nerve Injury

Chronic neuropathic pain is a frequent outcome of nervous system injury affecting the somatosensory system, and its pathobiology is dependent on activation and disinhibition of nociceptive neurons. It is characterised by spontaneous pain, dysaesthesia/paraesthesia as well as hypersensitivity to normally non-painful (allodynia) and painful (hyperalgesia) mechanical and thermal stimuli. Behavioural disabilities, such as depression, insomnia and alterations in social behaviours, are also co-morbid with changes in sensation. To investigate the mechanisms which result in neuropathic pain, animal models of neuropathy were developed by performing standardised, reproducible nerve injuries via surgical manipulation of a peripheral nerve. Here, we present four commonly used models in laboratory rodents for the study of neuropathic pain: (1) chronic constriction injury of the sciatic nerve, (2) partial sciatic nerve ligation, (3) L5 and/or L6 spinal nerve ligation and (4) the spared nerve injury, where two of the three terminal sciatic branches are cut. Rodents which have undergone any one of these procedures routinely display increased pain responses, such as allodynia and hyperalgesia of the hindpaw, lasting up to several months. Investigators should be aware however that such animal models suffer from several limitations including inconsistency in predicting the clinical success of novel therapeutics, poor correlation with clinical neuropathic pain in terms of prevalent symptoms and timescale and the need to assess operant/affective behavioural responses in addition to reflexive withdrawals from mechanical and thermal stimuli. Despite these limitations, animal models of peripheral nerve injury combined with testing of pain hypersensitivity remain necessary to investigate the pathophysiological mechanisms and identify novel therapeutic agents to treat chronic neuropathic pain.