Animal models of toxic and metabolic sensory neuropathies

Abstract

Peripheral neuropathies, excluding those caused by mechanical damage, are most commonly associated with infection, autoimmune disorders, and exposure to neurotoxins or metabolic disease. The sensory nervous system may be selectively damaged, as occurs in platinum toxicity, or there may be a more generalized sensorimotor neuropathy. Symptoms of sensory dysfunction range from sensory loss to inappropriate or exaggerated pain perception and a variety of sensory disorders may occur together or in chronological sequence. For example, while sensory loss is the predominant symptom of diabetic polyneuropathy, 5-10% of patients exhibit a painful neuropathy that may either precede or co-exist with sensory loss. Pain, paresthesias or dysesthesias are a common feature of many peripheral neuropathies but are difficult to quantify in animal models. It is particularly unfortunate that both leprosy and HIV have proven extremely difficult to model in animals that lend themselves to experimental studies of nociceptive processing. As a result, little is yet known of the mechanisms that produce these most prevalent of neuropathies. In recent years, sensory dysfunction has been described in animal models of chemical neurotoxicity and diabetes mellitus. Such models are of value as they allow investigation of the etiology of neuropathic pain and because they provide test systems in which to study potential therapeutic agents that may prevent or ameliorate neuropathic pain. In this chapter we will briefly consider the animal models of toxic neuropathies, which largely produce sensory loss, and then focus upon data obtained from the widely studied animal models of diabetic neuropathy.