Abstract

Background and purpose

A noxious stimulus does not necessarily cause pain. Nociceptive signals arising from a noxious stimulus are subject to modulation via endogenous inhibitory and facilitatory mechanisms as they travel from the periphery to the dorsal horn or brainstem and on to higher brain sites. Research on the neural structures underlying endogenous pain modulation has largely been restricted to animal research due to the invasiveness of such studies (e.g., spinal cord transection, brain lesioning, brain site stimulation). Neuroimaging techniques (e.g., magnetoencephalography (MEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)) provide non-invasive means to study neural structures in humans. The aim is to provide a narrative review of neuroimaging studies related to human pain control mechanisms.

Methods

The approach taken is to summarise specific pain modulation mechanisms within the somatosensory (diffuse noxious inhibitory controls, acupuncture, movement), affective (depression, anxiety, catastrophizing, stress) and cognitive (anticipation/placebo, attention/distraction, hypnosis) domains with emphasis on the contribution of neuroimaging studies.

Results and conclusions

Findings from imaging studies are complex reflecting activation or deactivation in numerous brain areas. Despite this, neuroimaging techniques have clarified supraspinal sites involved in a number of pain control mechanisms. The periaqueductal grey (PAG) is one area that has consistently been shown to be activated across the majority of pain mechanisms. Activity in the rostral ventromedial medulla known to relay descending modulation from the PAG, has also been observed both during acupuncture analgesia and anxiety-induced hyperalgesia. Other brain areas that appear to be involved in a number of mechanisms are the anterior cingulate cortex, prefrontal cortex, orbitofrontal cortex and nucleus accumbens, but their exact role is less clear.

Implications

Neuroimaging studies have provided essential information about the pain modulatory pathways under normal conditions, but much is still to be determined. Understanding the mechanisms of pain control is important for understanding the mechanisms that contribute to failed pain control in chronic pain. Applying fMRI outside the brain, such as in the trigeminal nucleus caudalis of the spinotrigeminal pathway and in the dorsal horn of the spinal cord, and coupling brain activity with activity at these sites may help improve our understanding of the function of brain sites and shed light on functional connectivity in the pain pathway.