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Table 1 Examples of Contributions by fMRI on the understanding Brain Regions activated by Acute Pain

From: Breaking down the barriers: fMRI applications in pain, analgesia and analgesics

STUDY FOCUS REFERENCE MAJOR FINDINGS COMMENT
Peripheral Nerve    
Trigeminal Ganglion (TG) Borsook et al., 2003. [63] Somatotopic activation in the trigeminal ganglion Measures of the peripheral nervous system may be evaluated using fMRI
Dorsal Horn    
Trigeminal Nucleus (TN) DaSilva et al., 2002. [20] Somatotopic acitivation in the TN Study reports that pain spinal cord brainstem systems can be defined and somatotopically evaluated.
Brainstem    
Periaqueductal Gray (PAG) Becerra et al., 2001 [17] Both increases (early) and decrease (late) of activation may correlate with ascending and descending (modulatory) components of functioning within this structure. The PAG is a 'core' structure in understanding how the brain modulates pain, both in placebo and in the effects of analgesics, particularly opioids.
Right Cuneus Fulbright et al., 2001 [64] Cold pressor induced pain produced activation in a number of regions including the frontal lobe and the cuneus. Measures of affective components of cold pain.
Brainstem NucleiCuneiformis, parabrachial, PAG, red nucleus Dunckley et al., 2005 [65] Activation to somatic and visceral pain. A big step forward in measures of brainstem measures of pain in humans. Marked similarities in the two processes were observed at a brainstem level.
Subcortical Gray Regions    
Emotion CircuitryAccumbens, SLEA, Amygdala, Hippocampus, Hypothalamus, Oribitofrontal Cortex Becerra et al., 2001 [17] Acute pain activates circuitry that is commonly associated with reward. Emotional circuitry is activated ahead of sensory circuitry The first demonstration that reward circuitry can be mapped in acute pain.
Amygdala Seymour et al., 2005 [21] Termination of pain (rewarding) activates the amygdala The significance of understanding the brain systems to natural reward (i.e., pain relief).
Putamen Bingel et al., 2004 [66] 15 Subjects. Laser evoked pain to foot or hand produced contralateral somatotopic organization in putamen Clear activation in putamen by pain indicative of potential role in emotional or motor processing of pain.
Accumbens (NAc) Aharon et al., 2006 [18] Acute noxious (but not non-noxious) stimuli activate the NAc. Within the structure, different signals may indicate functional processing within the 'core' and 'shell' of the structure. A number of regions have different functional components (e.g., amygdala, PAG) and the ability to dissect apart these within a set paradigm will contribute further to mechanistic functions of pain processing in humans.
Cortical Regions    
Anterior Cingulate(aCG) Becerra et al., 1999 [10], 2001 [17] One of the first fMRI studies to demonstrate differential aCG activation in the structure. Differentiation of sensory vs. emotional components of aCG function.
Hippocampus (Hi) Ploghaus et al., 1999 [27], 2000 [67], 2001 [28] Hippocampal activation correlates with anxiety/ Papers address a specific function of the hippocampus in pain and further show a correlation with insula activity.
Insula (I) Brooks et al., 2005. [19] Somatotopic organization in the insula defined The insula has been a bit of an enigma. Based on preclinical work, human work seems to support the notion that the insula is receives thermal information from the ventromedial nucleus of the thalamus (VMpo) specific thermal stimuli
Oribtofrontal Cortex (GOb) Rolls et al., 2003. [68] Effects of pleasant and painful touch to hand. Oribitofrontal activation > pleasant or pain vs. neutral. SI less activated by pleasant and pain than neutral touch. Regional differences in aCG to pleasant (rostral aCG) and pain (posterior dorsal). Brainstem (e.g., PAG) activated by all 3 touch stimuli. Clear dissociation between sensory and emotional systems to 'reward' and aversion.
Somatosensory Cortex Bingel et al., 2004 [66] Painful laser stimuli applied to hand and foot produced somatotopic organization in contralateral and ipsilateral SI cortex. Laser stimuli can provide stimuli without tactile components.