Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems

Abstract

Myofascial pain of the temporomandibular region (M-TMD) is a common, but poorly understood chronic disorder. It is unknown whether the condition is a peripheral problem, or a disorder of the central nervous system (CNS). To investigate possible CNS substrates of M-TMD, we compared the brain morphology of 15 women with M-TMD to 15 age- and gender-matched healthy controls. High-resolution structural brain and brainstem scans were carried out using magnetic resonance imaging (MRI), and data were analyzed using a voxel-based morphometry approach. The M-TMD group evidenced decreased or increased gray matter volume compared to controls in several areas of the trigeminothalamocortical pathway, including brainstem trigeminal sensory nuclei, the thalamus, and the primary somatosensory cortex. In addition, M-TMD individuals showed increased gray matter volume compared to controls in limbic regions such as the posterior putamen, globus pallidus, and anterior insula. Within the M-TMD group, jaw pain, pain tolerance, and pain duration were differentially associated with brain and brainstem gray matter volume. Self-reported pain severity was associated with increased gray matter in the rostral anterior cingulate cortex and posterior cingulate. Sensitivity to pressure algometry was associated with decreased gray matter in the pons, corresponding to the trigeminal sensory nuclei. Longer pain duration was associated with greater gray matter in the posterior cingulate, hippocampus, midbrain, and cerebellum. The pattern of gray matter abnormality found in M-TMD individuals suggests the involvement of trigeminal and limbic system dysregulation, as well as potential somatotopic reorganization in the putamen, thalamus, and somatosensory cortex.

Different Pain, Different Brain: Thalamic Anatomy in Neuropathic and Non-Neuropathic Chronic Pain Syndromes

“…For example, fibromyalgia, a condition similar to TMD, is associated with changes in amygdala, cingulate, prefrontal, and insular cortex volumes (Kuchinad et al, 2007); Burgmer et al (2009) and Younger et al (2010) recently reported increased thalamus, insula, and putamen volumes in TMD patients. Even at a lowered statistical threshold of uncorrected p Ͻ 0.01, significant gray matter volume increases in these regions failed to emerge.…”

“…Alternatively, it has been reported that repeated noxious stimulation in healthy controls results in increased gray matter volume in the primary somatosensory and cingulate cortices (Teutsch et al, 2008). Because TMD results primarily from constant nociceptor activation, it is possible that the gray matter increases reported by Younger et al (2010) reflect adaptive changes attributable to constant activity that subside over time. Furthermore, it has been reported recently that volume decreases in regions that process emotional state changes, e.g., the insula cortex, are related to the fibromyalgia patient's affective state and not the presence of pain per se (Hsu et al, 2009).…”

“…Although most chronic pain investigations have focused on peripheral targets such as nociceptors and their terminations, there is evidence that changes within higher brain centers may also be important for the maintenance and/or development of some chronic pain conditions. For example, many chronic pain conditions are associated with gray matter losses in a number of brain regions associated with acute pain processing, i.e., primary and secondary somatic areas, insula, thalamus, and cingulate cortex (Apkarian et al, 2004;Kuchinad et al, 2007;Schmidt-Wilcke et al, 2007;Buckalew et al, 2008;DaSilva et al, 2008;Kim et al, 2008;Schweinhardt et al, 2008;Burgmer et al, 2009;Gustin et al, 2010;Younger et al, 2010). Despite numerous investigations reporting brain anatomy changes associated with chronic pain, it remains unknown what these gray matter changes represent and whether these changes are uniformly expressed in all chronic pain conditions regardless of their etiology.…”

“…Furthermore, VP thalamic stimulation can produce pain (Lenz et al, 1993;Davis et al, 1996) and increased thalamic bursting activity and biochemical changes indicative of neuronal loss occur in patients with pain after spinal cord injury (Lenz et al, 1989;Pattany et al, 2002). In direct contrast to neuropathic pain conditions, pain associated with temporomandibular disorders (TMD) results primarily from the activation of peripheral nociceptors (Sarlani and Greenspan, 2005;Ro, 2008;Sessle et al, 2008;Manfredini and Nardini, 2010) and, furthermore, is associated with thalamic gray matter volume increases (Younger et al, 2010). Given this, it is possible that the thalamus plays differential roles in the maintenance and/or generation of different forms of chronic pain.…”

A Proposed Diagnostic Classification of Patients With Temporomandibular Disorders: Implications for Physical Therapists

“…22,32,74,75 Central nervous system differences in the trigeminal nucleus and limbic structures have been demonstrated in people with myofascial pain, and chronic pain results in sympathetic nervous system overactivation. 88 Carlson et al 12 summarized research demonstrating that people with chronic TMDs are physiologically overreactive to their environment and tend to have substantial psychosocial stressors compared to people without TMDs. Okeson 61 described the relationship of Axis I (physical) and Axis II (psychological) domains as shifting in balance as the time lengthens in which the individual's pain persists, with Axis II domains (eg, anxiety, depression, anger, fear) becoming more dominant over time.…”