Table 1.
Overview of clinical and preclinical studies on the insula in trigeminal neuropathic pain
| Subject condition | Stimulation method | Analyzing procedure | Brain region | Findings | Reference |
|---|---|---|---|---|---|
| TNP | Innocuous brushing of the lip | VBM | Ipsilateral AIC | Reduced GMV | [42] |
| TNP | Innocuous brushing of the lip | VBM | Contralateral PIC | Increased GM | [42] |
| TN | Light tactile stimulation | VBM, CTA | Ipsilateral AIC and PIC | Decreased cortical thickness | [26] |
| TN | Light tactile stimulation | VBM | Ipsilateral IC | Reduced GMV | [105] |
| TN | Daily activities (talking, chewing) | DWI, SIFT, SVM | Bilateral IC | Altered WMV connectivity and microstructural integrity | [107] |
| TNP | Daily activities (talking, chewing) | fMRI | Ipsilateral AIC, bilateral PIC | Decreased cortical thickness | [47] |
| TN | Electrical stimulation, tapping or lightly touching the skin | VBM | IC | Reduced GMV | [73] |
| TN | Daily activities | VBM, CTA | Right Ventral AIC and bilateral PIC | Reduced GMV by 9% and 10.4% | [27]. |
| TNP | Mechanical (brush) and thermal (cold and heat) | fMRI | AIC | Increased activity | [8] |
| Healthy | Gaseous CO2 trigeminal stimuli | fMRI | Operculo-Insula | Increased activity | [68] |
| TN | Classical precipitating factors (speaking, swallowing, shaving, yawning, etc.) | CTA, 3D vertex-wise analysis | Left IC | Reduced local gyrification index and decreased cortical thickness | [100] |
| TN | Classical precipitating factors (speaking, swallowing, shaving, yawning, etc.) | fMRI | Contralateral AIC | Increased activity | [72] |
| TN | Thermal and pulsed radiofrequency | fMRI | Both AIC and PIC | Enhanced BOLD signal | [1] |
| TN | Classical precipitating factors (speaking, swallowing, shaving, yawning, etc.) | VBM | IC | Reduced GMV | [99] |
| CCI-ION rat | Light, moving strokes on the infraorbital skin | IFC | AIC (Dysgranular, agranular) | Increased ERK phosphorylation | [3] |
| CCI-ION rat | Electrical and mechanical noxious stimulation | IFC, WB, electrophysiology | IC (Granular, dysgranular) | Increased pERK-CREB pathway, decreased neural activity | [98] |
| Pl-ION rat | Electrical stimulation of mandibular molar pulp | IFC | Insular oral region | Enhanced neural activity | [80] |
| Naïve rat | Mechanical stimulation with wire | High-resolution epicortical evoked potential mapping | AIC | Decreased activity | [10] |
| Naïve monkey | Noxiuos cold stimuli | fMRI | Dorsal PIC | Increased activity | [18] |
| Chronic corneal pain mice | Chemical corneal sensitivity test | fMRI | IC | Upregulated amplitude of low-frequency fluctuation (ALFF) | [103]. |
| Adult male C57BL/6 mice | In vitro chemical (α-CGRP and CGRP8–37) stimulation | Whole-cell patch-clamp recording | IC | Enhanced presynaptic glutamate release | [66] |
| adult vesicular GABA transporter (VGAT)-Venus line A transgenic rats | In vitro injection of depolarizing and hyperpolarizing current pulses | Multiple whole-cell patch-clamp recordings | IC | Increased excitatory presynaptic currents (pEPSC) amplitudes | [77] |
| CCI-ION rat | Mechanical and thermal stimulation | IFC | dPIC | Increased glutamatergic neural activity and enhanced CREB and pERK expression | [50] |
| Trigeminal nerve transection rat | Electrical stimulation | In vivo optical imaging, whole-cell patch-clamp recording | Layer II/III dorsal IC | Increased neural activity | [35] |
TN = trigeminal neuralgia, TNP = trigeminal neuropathic pain, fMRI = functional magnetic resonance imaging, AIC = anterior insular cortex, PIC = posterior insular cortex, WMV = white matter volume, GMV = gray matter volume, BOLD = blood oxygen level-dependent. CCI-ION = chronic constriction injury of the infraorbital nerve, IFC = immunofluorescence, WB = western blot, RAIC = rostral agranular insular cortex, dPIC = dysgranular posterior insular cortex, DWI = diffusion-weighted magnetic resonance imaging, SVM = support vector machine classification, VBM = voxel-based morphometry, CTA = cortical thickness analysis