Patterns of Cerebral Activation to Innocuous and Noxious Heat Stimulations in Neuropathic Pain

Many patients with neuropathic pain exhibit hyperalgesia and allodynia. In various pain syndromes, neuropathic pain is among the most difficult to treat. Previous studies show that the development of secondary hyperalgesia results from abnormal processing of nociceptor input after injuries of the peripheral nervous system. However, the modulating effect on pain processing in brain by peripheral mechanisms remains elusive, and only few studies investigate the issue.

Evidences suggest that lesions of the spinothalamocortical pathway may be necessary for developing the central pain, indicating indirect changes in excitability due to alterations of pain modulatory systems. Previous anatomical, physiological, and lesion studies have revealed an extensive cortical network associated with sensory, cognitive, and affective aspects of pain, including primary somatosensory cortex, secondary somatosensory cortex, insular cortex, and anterior cingulate cortex. Moreover, a recent study reported that neuropathic pain might influence brain organization. Therefore, it would be intriguing to know whether and how the brain processes pain in patients with neuropathic pain.

We hypothesize that neuropathic pain elicited by the peripheral neuropathy results in hyperexcitability of the pain matrix (i.e. central sensitization) due to alterations of pain modulatory systems. Patients with peripheral neuropathy and healthy volunteers will be recruited in this study. Peripheral neuropathy is defined according to the neuropathic symptoms and signs. For healthy volunteers, clinical history will be evaluated by questionnaires and neurological examinations to exclude any neuropsychiatric disorder or pain condition.

To assess the severity of different neuropathic symptoms,patients with neuropathic pain will fill out the Neuropathic Pain Symptom Inventory (NPSI). Each subject will receive detailed sensory examination to evaluate the integrity of small-diameter and large-diameter sensory fibers. To measure thresholds of thermal and vibratory sensations, we will perform quantitative sensory testing (QST) by the method of level using a Thermal Sensory Analyser and Vibratory Sensory Analyser (Medoc Advanced Medical System, Minneapolis, MN, USA) following an established protocol. Thermal thresholds will be recorded on the toe, and vibratory thresholds recorded on the lateral malleolus. These values will be compared with normative values for the age, which had been documented previously.

Functional magnetic resonance imaging (fMRI) will be performed on a 3-T MR machine (Trio; Siemens, Erlangen, Germany). A high resolution T1 weighted scan of the entire brain in trans-axial orientation will be obtained to provide anatomical information for the superimposed functional activation maps. Echo Planar Imaging will be used for the acquisition of the functional data.