Current Understanding of the Involvement of the Insular Cortex in Neuropathic Pain: A Narrative Review

Abstract

Neuropathic pain is difficult to cure and is often accompanied by emotional and psychological changes. Exploring the mechanisms underlying neuropathic pain will help to identify a better treatment for this condition. The insular cortex is an important information integration center. Numerous imaging studies have documented increased activity of the insular cortex in the presence of neuropathic pain; however, the specific role of this region remains controversial. Early studies suggested that the insular lobe is mainly involved in the processing of the emotional motivation dimension of pain. However, increasing evidence suggests that the role of the insular cortex is more complex and may even be related to the neural plasticity, cognitive evaluation, and psychosocial aspects of neuropathic pain. These effects contribute not only to the development of neuropathic pain, but also to its comorbidity with neuropsychiatric diseases. In this review, we summarize the changes that occur in the insular cortex in the presence of neuropathic pain and analgesia, as well as the molecular mechanisms that may underlie these conditions. We also discuss potential sex-based differences in these processes. Further exploration of the involvement of the insular lobe will contribute to the development of new pharmacotherapy and psychotherapy treatments for neuropathic pain.

Side matters: differences in functional outcome and quality of life after thrombectomy in left and right hemispheric stroke

“…Moreover, patients with RHS suffer more frequently from the pusher-syndrome (lateropulsion) after stroke [ 20 ] which might also account for a worse perception of mobility. Interestingly, imaging studies revealed an increased activation of the right-sided insula in the presence of neuropathic pain [ 21 , 22 ], indicating a strong association of right hemispheric lesions with the perception of pain, consistent with our findings.…”

A Narrative Review of Neuroimaging Studies in Acupuncture for Migraine

“…Chronic pain can lead to persistent emotional disorders such as anxiety, fear, and influence brain processing on many levels [ 47 – 49 ]. Cumulative evidence suggested that ACC contributed to the response to the process of anxiety and fear of pain [ 50 , 51 ] and insula involved in the processing of the emotional motivation dimension of pain [ 52 , 53 ]. MFG is often referred to as the dorsolateral prefrontal cortex (dlPFC) [ 54 ], dlPFC is a core putative target for modulation of pain-related fear responses [ 55 ].…”

Synaptic Plasticity in the Pain-Related Cingulate and Insular Cortex

“…The IC also displays increased activity in response to different noxious stimuli such as gustatory, visceral, mechanical, and somatosensory nociceptive stimuli [ 34 ]. Consistent with these data, increasing inhibitory transmission in the IC can produce an analgesic effect and growing evidence strongly suggests that, like the ACC, the IC is indeed a highly plastic region that plays a key role in the psychosocial components of neuropathic pain [ 35 ]. A recent study has provided further evidence that the IC is critical for the perception, modification, and chronification of pain and that changes in the functional connectivity of IC networks in clinical studies are associated with changes in white and gray matter in the brain [ 36 , 37 , 38 ].…”