**10. Morphological and functional changes in the brain are associated with chronic pain**

Chronic pain conditions are associated with vast functional and structural changes of the brain, when compared to healthy controls, but it is currently unclear which comes first: does chronic pain cause distortions of brain circuitry and anatomy or do cerebral abnormalities trigger and/ or maintain the perception of chronic pain? Future studies will clarify these questions.

Brain abnormalities in chronic pain states include modification of brain activity patterns, localized decreases in gray matter volume, and circuitry rerouting [53]. Observation of overall brain activity patterns in a variety of chronic pain conditions has led to the discovery that spontaneous and evoked pain are uniquely represented in the brain [53]. Spontaneous pain associated with chronic back pain and PHN induce increased activity in the mPFC and amygdale while acute thermal pain and allodynia associated with PHN illicit larger responses in the thalamus and insula [53]. Similar activity patterns are observed in thermal and mechan‐ ical acute pain in healthy individuals and knee pain associated with osteoarthritis, all forms of evoked pain [53].

Chronic pain conditions are associated with localized reduction in gray matter volume, and the topography of gray matter volume reduction is dictated, at least in part, by the particular pathology. Chronic back pain, for example, is associated with a loss of bilateral dorsolateral prefrontal cortex and unilateral thalamic gray matter [57] while irritable bowel syndrome 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 changes have on individual pain perception remains to be determined.

pathophysiology, conventional treatments prescribed for nociceptive pain are not very effective in treating neuropathic pain and vice versa [78]. Therefore the first step towards

Neuropathic Pain: From Mechanism to Clinical Application

http://dx.doi.org/10.5772/55277

13

Identifying neuropathic pain in a clinical setting begins with a thorough review of the patient's history through evaluation of previous medical records and verbal communication with the patient. Standardized screening tools such as the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) [79], the Douleur Neuropathique en 4 questions (DN4) [12], and painDE‐ TECT [13] can guide clinician through a series of questions aimed at indentifying possible neuropathic pain. In completing these questionnaires patients are asked to describe their pain in terms of quality (i.e. pricking, tingling, pins and needles, electric shocks/shooting, burning) and context (i.e. provoked by heat, cold, or pressure) [80]. In addition to verbal descriptors, the LANSS and DN4 also include a short bedside examination of sensory abnormalities. Although each screening tool is unique, they have similar sensitivity and specificity, between 80-85% for both parameters [80]. This suggests that approximately 1 in 5 patients who fit the criteria for neuropathic pain as determined by the screening tool and 20% of all individuals who've been evaluated are misdiagnosed. This reaffirms that careful clinical judgment is

Additional information that is not included within the standardized questionnaires can also be useful in diagnosing neuropathic pain. Mapping pain topography allows the clinician to consider whether a lesion is anatomically logical, and descriptions of frequency (i.e. on-going, spontaneous) and intensity (e.g. mild, moderate, severe, excruciating or 1-10) can aid in

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

Treating neuropathic pain requires a multifaceted approach that aims to eliminate the underlying etiology, when possible, and manage the associated discomforts and emotional distress. Although in some cases it is possible to directly treat the cause of neuropathic pain,

meaningful pain relief is an accurate diagnosis.

necessary to make an accurate diagnosis.

identifying a potential mechanism [1].

**13. Clinical examination**

bedside sensory tests see Table 1.

**14. Pharmacological treatment of neuropathic pain**

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 resultant behaviors.
