**13. Clinical examination**

displays a volume reduction in the insula and cingulate cortex [58]. In addition, gray matter atrophy has been suggested to occur in a variety of pain conditions including fibromyalgia, knee osteoarthritis, and headaches [59-66]. These changes appear to represent a form of plasticity as they are reversible when pain is effectively managed [63, 67, 68]. How or why individual pathologies result in distinct morphological distortions and what impact these

12 Peripheral Neuropathy - A New Insight into the Mechanism, Evaluation and Management of a Complex Disorder

Changes in brain circuitry have also been reported in patients with chronic back pain [69]. Baliki et. al. found that when an acute thermal stimulus is applied to the skin of healthy subjects, activity in the NAc at the end of the stimulus response cycle is strongly correlated with the insula. This is distinct from patients with chronic back pain where activity in the NAc is strongly correlated with the medial prefrontal cortex (mPFC) [69]. The resulting activity in the NAc is divergent as the phasic response observed in healthy subjects has been correlated to the prediction of reward while the activity pattern in chronic pain patients represents lack of reward or disappointment [69]. Although there is no difference in the reported perceived magnitude of the stimulus, this suggests that subconsciously chronic pain patients are disappointed when an acute pain stimulus is removed, begging the question, what are the resultant cognitive and behavior manifestations? This opens up the field to a series of questions considering the effects of subconscious components of brain activity on perception of pain and

Persistent pain is the single most common ailment that brings people to a primary care physician each year, accounting for approximately 40% of all visits [70]. Measurements of overall health-related quality of life, a multidimensional construct that takes into account physical, emotional, and social well-being, are depressed in chronic pain patients [15], and the resulting work absenteeism and elevated health care costs represent a substantial economical and societal burden [71-74]. Although effective management of chronic pain would certainly reduce this burden, treatment options are inadequate and often wrought with adverse health effects [15]. It is becoming increasingly clear that the path towards efficacious pain manage‐ ment is one of individualized medicine that stems from an understanding of the underlying pathophysiology and resultant sensory abnormalities [31, 75-77]. Although this may be the future of pain management, the current understanding of an individual "sensory phenotype" and dearth of clinical trials utilizing this perspective prevent immediate implementation. The following sections will highlight the current evidence based methods of diagnosing and

treating neuropathic pain and suggest the future of research and clinical practice.

By definition, neuropathic pain indicates direct pathology of the nervous system while nociceptive pain is an indication of real or potential tissue damage. Due to the distinction in

changes have on individual pain perception remains to be determined.

resultant behaviors.

**12. Clinical history**

**11. Neuropathic pain diagnosis**

Evaluating sensory function in a bedside examination can be helpful in assessing neuropathic pain. Since a lesion of the nervous system will often manifest as decreased sensitivity in some sensory modalities and increased sensitivity in others, objectively measuring each sensory modality can aid in forming a diagnosis. Guided by the patient's history, the putative lesion innervation territory is tested while the contralateral side of the body serves as a control. Testing consists of touching the patient's skin with calibrated tools that elicit a response in a subset of peripheral neurons. For example, brushing the skin lightly will tests sensitivity of Aβ mechanoreceptors while a thermoroller will test heat sensitive C fibers [1]. For a list of bedside sensory tests see Table 1.
