Different pain, different brain: thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes

Abstract

Trigeminal neuropathic pain (TNP) and temporomandibular disorders (TMD) are thought to have fundamentally different etiologies. It has been proposed that TNP arises through damage to, or pressure on, somatosensory afferents in the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. Because some reports suggest that neuropathic pain is associated with changes in brain anatomy, it is possible that TNP is maintained by changes in higher brain structures, whereas TMD is not. The aim of this investigation is to determine whether changes in regional brain anatomy and biochemistry occur in both conditions. Twenty-one TNP subjects, 20 TMD subjects, and 36 healthy controls were recruited. Voxel-based morphometry of T1-weighted anatomical images revealed no significant regional gray matter volume change in TMD patients. In contrast, gray matter volume of TNP patients was reduced in the primary somatosensory cortex, anterior insula, putamen, nucleus accumbens, and the thalamus, whereas gray matter volume was increased in the posterior insula. The thalamic volume decrease was only seen in the TNP patients classified as having trigeminal neuropathy but not those with trigeminal neuralgia. Furthermore, in trigeminal neuropathy patients, magnetic resonance spectroscopy revealed a significant reduction in the N-acetylaspartate/creatine ratio, a biochemical marker of neural viability, in the region of thalamic volume loss. The data suggest that the pathogenesis underlying neuropathic and non-neuropathic pain conditions are fundamentally different and that neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus.

Figures

Figure 1.

Frequency (percentage of subjects) of the five most common pain descriptors and the frequency of temporal characteristics selected from the McGill Pain Questionnaire by patients with TNP (gray bars) or TMD (white bars). * indicates significant differences between groups at p < 0.05. Note that TNP was often described as shooting, radiating, and sharp, whereas TMD was most often described as throbbing, tender, and boring in nature.

Figure 2.

Glass brain views of gray matter volume changes in TMD and TNP patients compared with controls and in TMD patients compared with TNP patients. Note that TNP patients have significant regional changes in gray matter volume compared with controls, whereas TMD patients do not. Furthermore, note that there are significant gray matter volume differences between TMD and TNP patients.

Figure 3.

Regional gray matter volume decreases (cool color scale) and increases (hot color scale) in TNP patients compared with controls and compared with TMD patients. Gray matter volume changes are overlaid onto axial and coronal slices of an individual subject's T1-weighted anatomical image set. Slice locations are indicated on the 3-D brain in the top left and by the Montreal Neurological Institute space at the top left of each slice. Note that, compared with both control and TMD subjects, TNP patients have lower gray matter volumes in the ipsilateral (ipsi) anterior insula, putamen and primary somatosensory cortex (SI), and the contralateral (contra) thalamus. Furthermore, compared with control subjects, TNP patients also had decreased gray matter volume in the ipsilateral thalamus and the contralateral nucleus accumbens (NA).

Figure 4.

Gray matter volume decreases in the contralateral thalamus of TNP patients and contralateral (contra) thalamic activity increases during innocuous brushing of the lower lip overlaid onto axial slices of an individual subject's T1-weighted anatomical image set. Light blue indicates gray matter volume decrease, red indicates activity increases during lip brushing, and yellow indicates where both gray matter volume decreased and activity (signal intensity) increased. Slice location in Montreal Neurological Institute space is indicated on the bottom right of the left slice. Bottom left shows mean ± SEM percentage change in signal intensity plotted against time for the contralateral thalamus. The gray bars indicate the periods during which the lower lip was lightly brushed with a plastic brush. Bottom middle and right show plots of gray matter volume decrease (prob * vol) in the area of overlap (i.e., yellow shading, the ventroposterior thalamus) against ongoing diary pain, as indicated on a continuous visual-analog scale (VAS) (bottom middle) and against pain duration (bottom right). Note the significant negative correlation between gray matter volume and pain, i.e., the greater the pain, the greater the reduction in gray matter volume.

Figure 5.

Top, Thalamic region in which gray matter volume decreased (measured using VBM) in TNP patients compared with controls, overlaid onto an individual subject's T1-weighted anatomical axial image. Bottom, Mean ± SEM gray matter volumes in the thalamic region indicated on the left, in controls, all TNP patients (trigeminal neuralgia and neuropathy combined), trigeminal neuralgia, and trigeminal neuropathy patients, respectively, from left to right. It is clear that thalamic gray matter volume loss in TNP patients is because of the volume loss in the trigeminal neuropathy patients but not the trigeminal neuralgia patients.

Figure 6.

Top, Thalamic region in which gray matter volume decreased in TNP patients and region from which H1-spectra were collected. To the right is a typical H1-spectra. PCr, Phosphocreatine. Bottom, Left, NAA/Cr within the ventroposterior thalamus in controls, TMD, and trigeminal neuropathy patients on the side ipsilateral (unaffected side) and contralateral (affected side) to ongoing pain. Note that, although there is no significant change in NAA/Cr in TMD patients, NAA/Cr is significantly reduced in the thalamus on the side contralateral to the ongoing pain in trigeminal neuropathy patients. *p < 0.05.