Central mechanisms of pain revealed through functional and structural MRI.

MR-based brain imaging technologies provide a suite of functional and structural metrics that can be used to test hypotheses about the CNS mechanisms underlying pain perception and chronification, from a cellular level to a systems level. Two types of functional MRI discussed in this review provide insight into pain mechanisms: stimulus-evoked fMRI and task-free ("resting state") fMRI. The former can assess how the brain responds to noxious or non-noxious stimuli normally or in a chronic pain state as a window into understanding pain, hyperalgesia and allodynia. The latter can assess functional connectivity reflecting synchronous ultra-slow frequency oscillation between brain areas. This provides insight into how brain areas work together as networks to produce pain and how these networks may be modified due to chronic pain. Perfusion MR (e.g., arterial spin labeling) can also provide task-free information pertaining to ongoing brain activity that may reflect spontaneous (ongoing) chronic pain. Structural MR techniques can be used to delineate gray and white matter abnormalities and markers of neuroinflammation associated with chronic pains. Functional and structural MRI findings point to brain and peripheral nerve abnormalities in patients with chronic pain, some of which are pre-existing and others that develop with prolonged pain (and related neuroinflammation) over time. Recent studies indicate that some structural brain abnormalities associated with chronic pain are reversible following effective pain treatment. These data together with findings from studies of individual differences suggest that some chronic pains arise from a combination of pre-existing vulnerabilities and sustained abnormal input.