The insula: A multidimensional integration site for pain

Tracer and imaging studies have revealed patterns of connectivity relevant to pain processing within the mammalian central nervous system (Craig et al., 2002; Braz et al., 2005; Hadjipavlou et al., 2006). Disruption of these pathways may lead to specific abnormal pain or temperature sensation e.g. central pain. However, the existence of labelled lines conveying pain and thermosensory information to the brain is still controversial, and has provoked much debate in the literature (Wall, 1995; Willis et al., 2002). Neuroimaging techniques offer the possibility of testing the physiological relevance of connectivity patterns proposed by cell labelling studies, and have led to the usage of the term ‘‘pain matrix’’: comprised of the structures most frequently activated in experiments studying pain perception. However, the concept of a pain matrix, whose division is determined by distinct sensory-discriminative or affective-motivational components of the pain experience (Albe-Fessard et al., 1985), may be outdated (Treede et al., 1999; Tracey, 2005). For example, recent brain imaging studies are beginning to reveal subtleties of the pain experience, whereby activation within the putative pain matrix may be observed following imagined, hypnotic and empathetic pain (Singer et al., 2004; Raij et al., 2005) i.e. in the absence of any nociceptive input. Allocating specific features of pain perception (i.e. sensory or affective) to specific brain regions may be inappropriate and too simplistic an approach. This is particularly the case for the insular cortex. The insula nicely demonstrates the convergence of neuroanatomy and the multidimensional nature of pain. This phylogenetically ancient structure appears to receive information via a direct thalamo-insular connection (Craig, 2003): and can be thought of as a site for sensory and affective integration. Several lines of evidence support the prominent role of the insula in pain processing: it is the most frequently activated structure in FMRI studies of pain (Apkarian et al., 2005); electrical stimulation of the posterior insula produces pain and/or thermal sensations in distinct sites on the contra-