Pain in the claustrum

Abstract

Pain arises from coordinated activity across distributed brain networks. The claustrum, a thin subcortical nucleus with extensive bidirectional connectivity with the neocortex, has recently emerged as a potential hub in this network. Although historically difficult to isolate due to its thin anatomical structure and proximity to other pain-associated regions, recent advances in neuroimaging and circuit-specific manipulations have revealed new insights into its role in pain. This review synthesizes the evidence from human and animal studies and evaluates the evidential strength of current approaches, ranging from incidental reporting in whole-brain neuroimaging studies to claustrum-targeted imaging, electrophysiology and projection-specific manipulations. The literature suggests that the claustrum contributes to pain not as a primary sensory relay, but as a modulatory and integrative structure influencing various facets of cognition. We have organized these findings into three theory-guided frameworks: (1) sensory filtering of salient stimuli, (2) cognitive network engagement, and (3) offline consolidation of pain-related memory during rest and sleep. In chronic pain, claustrocortical function is altered in ways that map onto each of these frameworks, with rodent models pointing to depressed claustrocingulate output and loss of inhibitory control, and human imaging linking claustrum signals to catastrophizing, expectancy, and altered network recruitment. Taken together, the evidence highlights the claustrum as a promising but incompletely understood node in pain circuitry and underscores the need for more anatomically precise and mechanistically decisive studies to define its contribution to normal and pathological pain states.