fMRI is also being applied to the evaluation of analgesics (pharmacological MRI or phMRI). [57]. Examples are provided in Table 5.
Analgesic effects on brain systems or neural circuits (stimulus independent) – Many analgesics have direct CNS effects, and very little is known about how they act on the human brain. Such studies are most often performed in healthy volunteers. Here the direct effect of administration of a drug is observed without any stimulus paradigm. These types of studies allow for the interrogation of effects that may not be obvious (e.g., subcortical, subconscious), for integration of how drugs may have a role on intact brain systems that still may be the case in the chronic pain state, and for the evaluation of potential side effects of drugs. Our naloxone and morphine studies (see Table 4; [58,59]) have taken this approach and indicate the ability to evaluate direct drug effects even when there are no obvious psychophysical effects (naloxone) or well-described side effect profiles (morphine) that can be evaluated based on circuit activation (e.g., reward, sedation or analgesic circuits). [59]. The ability to define specific differences across classes of drugs (e.g., antidepressants, membrane stabilizers, opioids) may not only help focus on common areas of potential mechanisms but also provide information within different drug classes (e.g., antidepressants – tricyclics vs. serotonin norepinehprine reuptake inhibitors). Advances in this domain should lead to use of standardized fMRI trials for early phase evaluation of pharmacotherapies for pain [60].
Analgesic effects on acute or chronic pain (stimulus-dependent) – In this group, the effect of the drug is evaluated in subjects usually following an applied painful stimulus. A few examples of this type of approach include the studies of cyclooxygenase (cox) inhibitors [61] and amitriptyline [62] in chronic pain conditions and the effects of drugs on capsaicin-induced hyperalgesia (see Table 5). These approaches show that pharmacological evaluation of the CNS effects of drugs is possible, suggesting that fMRI can be used for objective assessments of drug efficacy; until now, all assessments of analgesic efficacy relied on subjective psychophysical measures.
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