Anterior insular cortex neurostimulation modulates sensory hypersensitivity and pain-related emotional behaviors in a rat model of chronic neuropathic pain.
Abstract
Background
AND
Aims
Chronic neuropathic pain (NP) is frequently accompanied by anxiety- and depression-like behaviors that contribute to functional impairment. The insular cortex plays a central role in pain processing and interoceptive regulation, with the anterior insular cortex (AIC) critically involved in integrating sensory inputs with emotional and behavioral responses. However, whether direct modulation of AIC activity can simultaneously regulate sensory hypersensitivity and pain-related emotional behaviors remains unclear. This study investigated the effects of electrical neurostimulation of the AIC (eAIC) on chronic NP and associated affective disturbances.
Methods
Male Wistar rats were subjected to chronic constriction injury (CCI) of the sciatic nerve to induce NP or to a Sham procedure. Twenty-one days after surgery, an independent group of animals received a single session of eAIC neurostimulation delivered via stereotaxically implanted electrodes using low-frequency deep brain stimulation parameters (20 μA, 100 Hz, 15 s). Mechanical and cold allodynia, as well as anxiety- and depression-like behaviors, were subsequently evaluated using established behavioral paradigms.
Results
The eAIC significantly attenuated mechanical and cold allodynia in CCI rats. In parallel, eAIC reduced anxiety-like and depression-like behaviors without altering general locomotor activity. These effects were selectively observed in neuropathic animals and were not detected in SHAM-operated controls.
Conclusion
These findings demonstrate that AIC activity regulates both sensory hypersensitivity and pain-related emotional behaviors in chronic NP. By showing concurrent modulation of nociceptive and affective dimensions, this study provides physiological evidence supporting the AIC as a key cortical node linking pain processing to emotional behavior and underscoring its relevance for integrative neuromodulatory strategies.