Table 5 Examples of Contributions of fMRI on Analgesics

Opioids

Remifentanil(short acting μ opioid)

Wise et al., 2004. [101]

Activation measured in insula to noxious stimulus in subjects receiving Rx.

Study evaluates time course and half life of action of Rx in brain region.

Remifentanil

Wise et al., 2002 [102]

Activation in brain regions to noxious heat stimulus in patients receiving Rx vs. saline. Rx produced decrease in level of pain activation in insula cortex.

First study to Evaluate CNS effects on stimulus; this allowed for extraction of regions most affected by the Rx.

NaloxoneOpioid (μ antagonist)

Borras et al., 2004. [59]

10 subjects. Direct drug effects indicated increased in aCG, prefrontal cortex, hippocampus and entorrhinal cortex. Post infusion painful heat produced increase in activation (correlated with psychophysical effects).

First study on opioids to address direct CNS effects. Naloxone is a drug that has no cognitive effects in normal healthy volunteers.

Morphine (μ agonist)

Becerra 2006. [58]

Low dose morphine produces changes in reward (SLEA, NAc, GOb) endogenous analgesia (PAG), and hypnotic circuits.

fMRI of the effects of morphine on CNS circuits – indicating the use of this approach to define specific circuitry activated by a drug.

Antiseizure meds

Gabapentin

Ianetti et al., 2005 [41]

Healthy volunteers. In a capsaicin model, single dose gabapentin has an antinociceptive effect but a stronger antihyperalgesic effect: the study indicates that the drug is more effective in the sensitized state.

An excellent example of the application of fMRI to drug evaluation in dissecting the value of a model with potential clinical relevance.

Anti-inflammatory

Cyclogoxygenase-2 inhibitor (Cox 2)

Baliki et al., 2005 [61]

Patient with psoriatic arthritis. Single subject evaluation. Activation induced by palpating joints included thalamus, insula, SI, SII, aCG. Rx produced decrease at 1 h.

An example of specific application on evaluating efficacy of Rx. No drug site of action could be detected in this study.

Antidepressant

Amitriptyline

Morgan et al., 2005 [62]

Evaluation of rectal pain in patients with irritable bowel syndrome. Rx produced a decrease in activation in aCG, parietal association cortex.

Another example of how the focus on efficacy (CNS) of drugs may be evaluated.