Rodent models of neuropathy

The most commonly used nerve injury models are: the chronic constriction injury (CCI) of sciatic nerve,7 the partial sciatic nerve ligation (PNL) model,8 the spinal nerve ligation (SNL)/transection model (Figure 1.2),9 and the spared nerve injury (SNI) model.6 All models are associated with the development of hypersensitivity to thermal (heat and cold), and mechanical stimuli which are used experimentally as correlates of hyperalgesia and allodynia symptoms in neuropathic pain patients.10 However, the relevance of these measures to the human condition is questionable.

The CCI model consists of the loose ligation of the sciatic nerve with chromic gut sutures. An inflammatory reaction develops and consequentially damage to most A-fibers and some C-fibers. It is likely that there is a significant inflammatory component in the development e cc e cc

Chronic Constriction Injury Model

Figure 1.1 Graphical representation of (a) allodynia, a painful response to a normally innocuous stimuli and (b) hyperalgesia, an increased response to a normally painful stimulus. Stimulus intensity versus response relationship for noxious and innocuous stimuli. © The Board of Management and Trustees of the British Journal of Anaesthesia. Adapted from Bridges et al., 20015 by permission of Oxford University Press/ British Journal of Anaesthesia.

Stimulus intensity (b)

Stimulus intensity (b)

Figure 1.1 Graphical representation of (a) allodynia, a painful response to a normally innocuous stimuli and (b) hyperalgesia, an increased response to a normally painful stimulus. Stimulus intensity versus response relationship for noxious and innocuous stimuli. © The Board of Management and Trustees of the British Journal of Anaesthesia. Adapted from Bridges et al., 20015 by permission of Oxford University Press/ British Journal of Anaesthesia.

Some figures in the printed version of this book are not available for inclusion in the eBook for copyright reasons.

Figure 1.2 Rodent models of nerve injury. Many rodent models are based upon injury to the peripheral, usually sciatic, nerve. Schematic drawing of partial sciatic nerve injury (PSNL), chronic constriction injury (CCI), spared nerve injury (SNI), and spinal nerve ligation or transection (SNL/SNT) of the L5 and L6 spinal nerves. Adapted from Decosterd and Woolf, 20006 by permission of the International Association for the Study of Pain.

aforementioned animal models do not precisely mirror the "normal" human response to nerve injury. Second, for good ethical reasons, most animal models of neuropathic pain study the animals for a period of weeks, whereas the clinical course of neuropathic pain presenting to a pain relief clinic is often measured in years. Finally, as with all animal models, it is difficult to know what is actually perceived by the animal. To date, the behavioral manifestation of pain in rodent models of neuropathic pain has relied largely on measuring alterations in cutaneous sensory thresholds via measurement of reflex withdrawal thresholds to stimuli, such as punctuate mechanical (such as von Frey filaments),13 which are not without their shortcomings, heat (such as the infrared heating device14) or cooling (such as the application of acetone) stimuli. Whilst these hypersensory phenomena do occur in a subset of humans with neuropathic pain, they are more usually observed in response to mechanical rather than thermal stimuli. (It must be noted that because the terms hyperalgesia and allodynia are defined in terms of pain, and we cannot yet measure pain in rodents, the use of these terms in the context of animal studies is inappropriate. We will therefore use the term "hypersensitivity" in the context of animal studies.)

Therefore, there is a need for the development of more clinically relevant animal models of neuropathic pain, as well as more complex behavioral tests designed to measure a spontaneous ongoing pain phenotype, and pain comorbidity.

of the painful neuropathy.11 In the PNL model, a tight ligation is created around 33-50 percent of the sciatic nerve, leaving the rest of the nerve "uninjured."8 The SNL model traditionally consists of injury to the L5 and L6 spinal nerves, which contribute to the sciatic nerve.9 However, a transection of the L5 spinal nerve alone results in comparative symptoms and hence some experimenters now use this as a modified SNL model.5 This model is favorable to mixed injury models as it allows the examination of cellular responses of injured afferents (with cells in the L5/L6 dorsal root ganglia (DRG)) versus uninjured afferents (in the L4 DRG), and their relative importance in neuropathic pain.12 The spared nerve injury model involves tight ligation and lesion of the tibial and common peroneal nerves.6 This model allows testing of distinct regions of the hindpaw which are either innervated by injured or uninjured neurons, as well as separating degenerating neurons from uninjured neurons to a greater level.

Although commonly used and reproducible, there are shortcomings of these animal models which need to be considered. First, while neuropathic pain can be a devastating consequence of nerve injury in humans, the majority do not develop neuropathic pain following nerve injuries,3 whereas most animals do develop reflex hyper-sensitivity in response to the above injuries. Therefore, the

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

This guide will help millions of people understand this condition so that they can take control of their lives and make informed decisions. The ebook covers information on a vast number of different types of neuropathy. In addition, it will be a useful resource for their families, caregivers, and health care providers.

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