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.

Pain and Plasticity: Is Chronic Pain Always Associated with Somatosensory Cortex Activity and Reorganization?

“…Thalamic reorganization occurs following sectioning of peripheral afferents (Garraghty et al, 1991), sensory thalamus stump representations expand in amputees (Davis et al, 1998), and, following complete spinal cord injury, ventral thalamus cells that would normally respond to inputs from upper extremities respond to inputs from the neck and occiput (Lenz et al, 1987). Since neuropathic pain conditions are associated with changes in thalamic anatomy and biochemistry (Pattany et al, 2002;Gustin et al, 2010Gustin et al, , 2011 and thalamic lesions often result in neuropathic pain (Klit et al, 2009), changes in thalamic function may result in neuropathic pain by altering firing patterns of thalamocortical loops (Sarnthein and Jeanmonod, 2008).…”

Pathophysiological implication of CaV3.1 T-type Ca2+channels in trigeminal neuropathic pain

“…There is increasing evidence that TNP is associated with anatomical and biochemical changes in the thalamus (14)(15)(16). Moreover, patients with TNP display significant reductions in thalamic volume and neural viability (15), indicating that altered thalamic anatomy, physiology, and biochemistry may result in disturbed thalamocortical oscillatory properties.…”

“…Abnormal thalamic activity has been investigated in patients with neuropathic pain (3-7, 10-13, 17, 18), including TNP (14)(15)(16). Furthermore, the potential role of thalamic burst firing in abnormally increased low-frequency oscillations has been proposed as a pathophysiological mechanism (2,12).…”

Macro- and microstructural alterations in migraine and cluster headache

“…In contrast, localised thalamic atrophy was detected in trigeminal neuropathy, but not in patients that were classified as having trigeminal neuralgia or temporomandibular disorders [80]. Using MR spectroscopy in the same study, reduced levels of N-acetyl-aspartate, a marker of neuronal viability was found in the affected thalami.…”

“…Using MR spectroscopy in the same study, reduced levels of N-acetyl-aspartate, a marker of neuronal viability was found in the affected thalami. The difference between the direction of thalamic volume changes in trigeminal neuropathy and other pain disorder in the trigeminal territory may lie in the different pathomechanisms; peripheral events were proposed in trigeminal neuralgia and temporomandibular disorder, while the reduced volume and neural viability suggest central mechanisms in trigeminal neuropathy [80]. In a recent study on trigeminal neuralgia gray matter volume reduction was described in the thalamus, insula, anterior cingulate cortex, primary somatosensory and orbitofrontal cortices, secondary somatosensory cortex, cerebellum, and dorsolateral prefrontal cortex [81].…”