Biology Reference
In-Depth Information
Chapter 14
ARA290 in a Rat Model of Inflammatory Pain
Andrew Dilley
Abstract
Chronic pain affects as many as one in five people. A proportion of patients with symptoms of neuropathic
pain do not have clinical signs of any obvious tissue or nerve injury. Such patients include those with dif-
fuse limb pain, back pain, and complex regional pain syndrome type 1. These patients remain a clinical
enigma. However, through the development of the neuritis model, it has become apparent that local nerve
inflammation in the absence of gross pathology (i.e., axonal degeneration and demyelination) may under-
lie part of the mechanisms of pain. In this chapter, we describe a method to induce the neuritis model. We
also describe in detail a reliable method to test for mechanical allodynia and heat hyperalgesia. Data that
demonstrates the potential benefits of the neuroprotective agent ARA290 in reducing pain behavior in the
neuritis model are presented.
Key words Sciatic nerve, Nerve inflammation, Neuropathic pain, Von Frey testing, Hargreaves'
method, Nociception
1
Introduction
Chronic pain is a debilitating condition that affects as many as one
in five people. It has huge economic impact through lost work days
and healthcare costs. For some patients with the symptoms of
neuropathic pain, routine clinical examination provides evidence of
a peripheral nerve injury. Much of our understanding of the physi-
ological mechanisms of pain in these patients has been gained
through the use of animal models such as the chronic constriction
injury, spinal nerve ligation and spared nerve injury models. In
these models, animals exhibit behavioral changes that are consis-
tent with clinical signs of allodynia and hyperalgesia ( 1-3 ).
Electrophysiological recordings from primary sensory neurons
reveal signs of increased excitability, whereby injured axons develop
ongoing (spontaneous) activity and become responsive to mechan-
ical stimulation from their regenerating tips ( 4-7 ). However, many
patients do not have injuries that are comparable to these models.
In fact a proportion of patients with chronic musculoskeletal pain
lack signs of nerve or tissue injury on routine clinical testing despite
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