Neural correlates of mechanical allodynia and hyperalgesia in the human brain in health and disease: a systematic review and activation-likelihood estimation analysis

ABSTRACT: Painful and nonpainful stimuli evoke distinct patterns of functional brain activity, particularly in secondary mechanical hyperalgesia and neuropathic pain-related structures. This meta-analysis aggregated the literature on the pattern of functional brain MRI and PET responses during these types of painful stimulation. PubMed and Web of Science database searches were used to find brain imaging responses to 4 different types of stimuli: nonpainful mechanical stimuli, painful mechanical stimuli, brush allodynia, and painful mechanical stimuli in a hyperalgesic zone. Our literature search encompassed 82 pain imaging studies published from 1999 to September 2023. The activation likelihood estimation technique was used to summarize the individual study results into meta-analytic statistical parametric maps. In healthy subjects, nonpainful mechanical stimuli primarily activated the left postcentral gyrus, bilateral precentral gyrus, and right insula while painful stimuli also recruited the bilateral cingulate gyrus. Participants with chronic pain showed similar activation patterns. However, contrasts between chronic pain patients and healthy participants revealed greater activation of the left cingulate gyrus and right insula. Brush allodynia and hyperalgesic stimuli also activated these brain regions in both healthy subjects and chronic pain patients to a lesser extent. These results further our knowledge of the neuronal networks underlying the complex experience of pain across the entirety of the human brain. We discuss the limitations of the literature, particularly the paucity of research in neural correlates of brush allodynia and mechanical hyperalgesia, and how these deficits may be addressed.