Research Review By Dr. Robert Rodine©


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Date Posted:

October 2010

Study Title:

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


Younger JW, Shen YF, Goddard G, Mackey SC.

Author's Affiliations:

Stanford University School of Medicine and the University of California, San Francisco.

Publication Information:

Pain 2010; 149: 222-228.

Background Information:

Temporomandibular disorders (TMD) are highly heterogenous and can involve the TMJ itself, the surrounding muscles of mastication, enveloping fascia and associated structures. In general, pain originating from the myofascial structures is considered to be a common cause of TMD (referred to henceforth as M-TMD).

M-TMD is processed by the trigeminal pain system, which contains numerous points for neural dysregulation. Additionally, this pain system has been identified as a potential region for central sensitization (1). As such, sensitization of the CNS with M-TMD becomes a distinct possibility which can make clinical management challenging to say the least. This may explain why many individuals with M-TMD often meet the classification criteria for fibromyalgia (another disorder thought to be associated with central sensitization) (2).

The authors of this paper hypothesized that patients with M-TMD may experience gray matter abnormalities. These changes are similar to those seen in other chronic pain patients, such as migraneurs, chronic back pain patients, chronic tension headache sufferers and those with irritable bowel syndrome. Therefore the purpose of this study was to investigate, via MRI, for the presence of CNS abnormalities in patients with myofascial pain of the tempormandibular joint complex.

Pertinent Results:

15 women with chronic, bilateral M-TMD were recruited. Their average age was 38 yrs (range 23-61, Standard Deviation [SD] 13.7). Pain duration in the subjects was 4.4 years (1-11, SD 2.9).

15 healthy, age-matched controls were also recruited, with similar exclusion criteria (see study methods below).

One case subject was excluded due to corrupted MRI data, leaving a remaining sample of 29 participants for the analysis.

MRI Results and Differences:
  • While older individuals displayed less total gray matter volume than did younger individuals, no differences were found between groups M-TMD subjects and controls.
  • However, when MRI contrast was reversed, the M-TMD group was found to have less gray matter volume in one region, posterior to the central gyrus within the primary somatosensory cortex.
  • When gray matter volume was analyzed regionally, the M-TMD group displayed greater gray matter volume within the right inferior frontal gyrus, the right anterior insula, the right posterior putamen, the left ventral posterior thalamic nucleus and the right globus pallidus.
  • Within the M-TMD group, clusters of increased gray matter were found in the areas of the trigeminal nuclei where sensory and motor nuclei are known to exist.
  • A significant cluster of increased gray matter was found anterior and medial to the right trigeminal nuclei (regionally located in the area of the medial lemniscus and spinothalamic tract).
Pain Associations:
  • Secondary analyses were conducted comparing regional gray matter volume differences with self-reported pain, duration of illness and pressure algometry readings.
  • Greater jaw pain was associated with less gray matter volume within the right rostral anterior cingulate cortex, right Brodmann area and the right posterior cingulate.
  • Duration of illness was associated with increased gray matter volume within the bilateral posterior cingulate, the right hippocampus, bilateral midbrain and the right cerebellar peduncle.

Clinical Application & Conclusions:

In summary, this study revealed differences between those with M-TMD and age-matched controls. Most notably, individuals with M-TMD were found to have abnormalities within the trigeminothalamocortical and limbic systems, which are significant areas of pain processing.

To start, bilateral abnormalities were found within the pons. The pons is the chief sensory nucleus for the trigeminal system. This is the beginning or entry point of the system centrally, whereby pain from myofascial structures around the TMJ is initially processed. From here, supraspinal projections become of interest with respect to sensitization.

To understand the supraspinal projections, we need to remind ourselves of the pathways. So - inputs from the spinal trigeminal nuclei project to the brainstem sensory nuclei, which project to the VP thalamic nucleus and then to the primary somatosensory cortex.

The VP thalamic nucleus demonstrates importance as it is the chief relay centre in the trigeminal sensory system. This area has been previously identified as an area of increased gray matter volume in pain patients (3) and now within patients suffering from M-TMD. This may be interpreted to mean that M-TMD patients demonstrate ‘enhanced facilitation of trigeminal sensory messages’ compared to the controls. Additionally, a bilateral increase in gray matter volume may indicate somatotopic adaptation to increased nociceptive signaling.

The third order projections then travel from the thalamus to the primary somatosensory cortex. Here subjects with M-TMD were found to have less gray matter volume as compared to controls. This obviously creates confusion given that one would expect to see an increase, due to the direct connection between the thalamus and the primary somatosensory cortex.

The limbic system (the affective system) also demonstrated abnormalities as the right putamen and globus pallidus (basal ganglia) showed increases in gray matter volume in the M-TMD patients. This is consistent with previous research showing similar changes in patients with chronic low back pain (3). This finding may support the theory of somatotopic reorganization.

The anterior insula was also affected. This area receives input from the thalamus and integrates emotional states. In essence, this connection concerns the experience of pain as well as the anticipation of pain.

The anterior and posterior cingulated cortices showed abnormalities in the M-TMD group. The importance of this stems from the identified connection between the anterior cingulate cortex and emotional processing (4) and the posterior cingulate’s influence on catastrophizing behavior (5).

Longer disease duration was associated with greater gray matter volume within the hippocampus and substantia nigra. This is significant as it may indicate what the authors referred to ‘compensatory analgesic adaptations’.

Interestingly, M-TMD subjects within this study mostly showed increases in gray matter volume. This contradicts previous research in the area showing that pain sufferers experienced more regional decreases in gray matter volume. The authors feel this is due to the difference in illness duration between studies. Within the current investigation, patients had experienced a mean illness duration of 4.4 years.

By comparison, existing research in the area feature patients with mean illness durations of 8.5-20.6 years. As such, the authors postulate that the short term response of peripheral pain may lead to increases in gray matter volume, while regional decreases result from prolonged exposure.

While continued research in this area is definitely needed, results from this study have clinical implication with respect to prognosis. As chronic myofascial pain of the temporomandibular joint results in gray matter abnormalities (‘neuroplastic chronification’), it affects both the processing of pain as well as the emotional, anticipatory and possibly coping responses of nociceptive stimuli. This should lead clinicians towards taking a broader psycho-social approach to care and incorporating behavioural interventions.

Study Methods:

Participants were recruited within a University based orofascial pain clinic. Inclusion criteria were:
  • age at least 18 years
  • a chronic myofascial pain syndrome diagnosed within the masticatory muscles
  • pain present within the TMJ for at least a 12 week period which is experienced at least 4 times per week, and an average pain intensity of at least 4/10 for at least 1 hour per day
  • pain identified in the jaw, temples, face or auricular area
Subjects were excluded if they were pregnant, currently using opioids or psychiatric medications, claustrophobic, suffered a moderate or severe psychiatric illness, suffered another chronic pain disorder (such as fibromyalgia) or another metabolic, vascular or neurologic disorder. No exclusions were necessary based on these criteria.

Patients were asked to rate their present jaw pain via an 11-point numerical pain rating scale. Pressure algometry was also used to measure pain, with the measure recorded when the patient could sustain maximum tolerated pressure over the right masseter muscle. This recording was not taken from the healthy control group.

Participants underwent a T1 weighted MRI of the brain. Morphometry as well as regional grey matter volume were recorded.

Study Strengths / Weaknesses:

The authors of this study made an excellent attempt to choose patients with minimal comorbidity and essential only one clinical entity – M-TMD. However, all but 5 subjects were taking an array of medication, Rx and OTC, in an attempt to deal with pain. The influence of this drug intake could not be determined.

Cases were matched to healthy controls in order to provide comparison, however limited information was provided on this group. Controls were taking no medications for other conditions and were not be suffering from a chronic pain or craniofacial disorder. However, no pressure algometry was taken from the control group. This information could have been useful, as it is now unknown what the objective differences would have been between groups.

While the study sample is small, the body of knowledge within this area is equally small. This study therefore adds support to the use of a larger and broader trial.

Additional References:

  1. Sessle BJ. Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 2000; 11: 57-91.
  2. Leblebici et al. Coexistence of fibromyalgia, temporomandibular disorder, and masticatory myofascial pain syndromes. Rheumatol Int 2007; 27: 541-4.
  3. Schmidt-Wilcke et al. Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients. Pain 2006; 125: 89-97.
  4. Morgane et al. A review of systems and networks of the limbic forebrain/limbic midbrain. Prog Neurobiol 2005; 75: 143-60.
  5. Seminowicz et al. Cortical responses to pain in healthy individuals depends on pain catastrophizing. Pain 2006; 120:297-306.