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

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.