Table 3 Examples fMRI Studies of Surrogate Models of Pain

Experimental Allodynia

Capsaicin induced secondary hyperalgesia

Baron et al., 1999 [81]

9 Subjects. Capsaicin injection induced secondary mechanical hyperalgesia. Painful mechanical stimulation produced activation in prefrontal cortex >> than in nonpainful mechanical stimulation

First fMRI study of capsaicin induced hypersensitivity. Activation in prefrontal cortex = attention and cogniitvie changes (e.g., planning).

Brainstem activation by capsaicin

Zambreanu et al., 2005 [82]

Heat-capsaicin model used. Punctate mechanical stimuli applied to region of secondary hyperalgesia. Stimuli in hyperalgesic vs. control region showed activation in contralateral brainstem, cerebellum, bilateral thalamus, contralateral SI and SII, middle frontal gyrus, parietal association cortex and brainstem (cuneiformis, superior colliculi, PAG.

First evaluation of contribution of brainstem in central sensitization.

Cognitive influences on hyperalgesia

Wiech et al., 2005. [83]

Capsaicin-induced heat hyperalgesia results in frontal and medial prefrontal cortex, insula, and cerebellum. Activity in medial prefrontal cortex and cerebellum modulated by cognitive task.

Study addresses interaction between motivational and cognitive functions and may provide some basis for evaluating similar changes in chronic pain.

Capsaicin allodynia

Maihofner et al., 2004. [39]

Region of allodynia produced by capsaicin and thermal kindling. Brush to normal skin results in SI, parietal association cortex, SII bilaterally, contralateral insula. Brush to allodynic skin resulted in some overlap to those observed for control in addition to inferior frontal cortex, and ipsilateral insula.

Subtraction (unaffected vs. affected skin) indicates that mechanical allodynia in regions that include SI, parietal association cortex, inferior frontal cortex, and insula.