The pain imaging revolution: advancing pain into the 21st century

Abstract

The great advances in brain imaging techniques over the last few decades have determined a shift in our understanding of chronic pain conditions and opened the door for new opportunities to develop better diagnoses and perhaps better drug treatments. Neuroimaging has helped shape the concept of chronic pain from a disease affecting mainly the somatosensory system, to a condition in which emotional, cognitive, and modulatory areas of the brain are affected, in addition to degenerative processes. All these contribute to the development and maintenance of pain symptoms and comorbid features, including alterations in anxiety, depression, and cognitive processes. In this article the authors review the current understanding of the brain changes in chronic pain and the developments made possible by the use of various brain imaging techniques. They also discuss the possible applications of brain imaging to developing a "pain phenotype" that could aid in diagnostic and treatment choices of chronic pain conditions.

Figure 1

Figure 1 A: Overview of pain pathways and altered neural systems in chronic pain White arrows: ascending and intracerebral pain pathways; Blue arrows: modulatory descending pathways. A: amygdala; ACC: anterior cingulate cortex; Cer: cerebellum; H: Hypothalamus; Ins: insula; l, m: lateral and medial thalamus; M1: primary motor cortex; NA: nucleus accumbens; PAG: periaqueductal gray; PFC: prefrontal cortex; PPC: posterior parietal cortex; S1, S2: primary and secondary somatosensory cortex; SMA: supplementary motor area. Figure 1 B: Schematic of anatomical sites and pathways that show changes in chronic pain. Left: Sensory-motor, emotional/affective, cognitive/integrative and modulatory regions are involved in the complex processing of pain, with some areas being involved in more than one pain domain. One example is insula, which contains a somatotopic representation of pain, and also processes emotional aspects of pain experience. Right: Loss of afferent fibers (a), loss and changes in function in the dorsal root ganglion (b), plasticity in the dorsal horn neurons (c), as well as changes in the brain areas that are processing sensory, emotional, cognitive and modulatory aspects of pain (right panel) (d) and in descending modulatory pathways (e) have been described.

Figure 1

Figure 1 A: Overview of pain pathways and altered neural systems in chronic pain White arrows: ascending and intracerebral pain pathways; Blue arrows: modulatory descending pathways. A: amygdala; ACC: anterior cingulate cortex; Cer: cerebellum; H: Hypothalamus; Ins: insula; l, m: lateral and medial thalamus; M1: primary motor cortex; NA: nucleus accumbens; PAG: periaqueductal gray; PFC: prefrontal cortex; PPC: posterior parietal cortex; S1, S2: primary and secondary somatosensory cortex; SMA: supplementary motor area. Figure 1 B: Schematic of anatomical sites and pathways that show changes in chronic pain. Left: Sensory-motor, emotional/affective, cognitive/integrative and modulatory regions are involved in the complex processing of pain, with some areas being involved in more than one pain domain. One example is insula, which contains a somatotopic representation of pain, and also processes emotional aspects of pain experience. Right: Loss of afferent fibers (a), loss and changes in function in the dorsal root ganglion (b), plasticity in the dorsal horn neurons (c), as well as changes in the brain areas that are processing sensory, emotional, cognitive and modulatory aspects of pain (right panel) (d) and in descending modulatory pathways (e) have been described.

Figure 2. Imaging Publications on Pain

We used Google Scholar (scholar.google.com) to search for articles containing the keywords “pain” and “functional magnetic resonance imaging” during 4-year intervals. Even though the total number of articles may be overestimated by this method, similar exponential increasing trends were seen with more stringent search terms.

Figure 3. Imaging Methods

(Sava et al., 2009, Mol Pain, Permission Pending)

Figure 4. Broad Applications of fMRI in Pain

(Borsook and Becerra, 2007 Permission Pending, Current Pain and Headache, 2007)