An Approach to Identify Nerve Injury-Evoked Changes that Contribute to the Development or Protect Against the Development of Sustained Neuropathic Pain

Abstract

Chronic neuropathic pain is a huge public health problem that compromises the quality of life of millions of individuals. There are many causes for chronic neuropathic pain, one of them being peripheral nerve injury occurring during surgery or trauma. Even when considering only those cases resulting from surgery about 2-10% of patients undergoing various surgeries (amputation, breast surgery, thoracotomy, inguinal hernia, coronary artery bypass surgery, caesarean section) develop chronic severe (disabling) pain (Kehlet et al., 2006). In the USA alone, there are approximately 80 million surgeries performed each year (Apfelbaum et al., 2003); if only 5% of those patients went on to develop severe chronic pain, ~4 million people would be added to the list of chronic pain patients each year. Of the patients attending chronic pain clinics, 20% have implicated surgery as one of the causes of their chronic pain and, in about half of these, it was the sole cause (Macrae, 2001). The intensity of acute postoperative pain is a good predictor of long-term pain; however, adequate control of acute postoperative pain does not always lead to a decrease in the incidence of developing long term pain (Perkins and Kehlet, 2000). To reduce the level of tissue injury during surgery, surgical procedures have been modified including those used for joint repair (Kehlet et al., 2006); mastectomy and breast reconstruction (Gahm et al.; 2010; Vadivelu et al., 2008) and herniorraphy (Nathan and Pappas, 2003; Pokorny et al., 2008); however, a significant percentage of patients still develop chronic pain. Hence, there is a need to develop treatments that can be used before and during the early phases following nerve injury (as a result of surgery or trauma) to prevent the development of chronic pain. The development of chronic pain following surgery correlates with the presence of peripheral nerve injury (Macrae, 2001). Studies using various peripheral nerve injury models have shown that these models share some, but not all, of the injury-induced molecular changes that may be contributing to chronic neuropathic pain (Berger et al., 2011; Xu and Yaksh, 2011). Moreover, whether changes in a given molecule contribute to