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Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.

ABSTRACT: Brain neuroimaging has been widely used to investigate the bran signature of chronic orofacial pain, including trigeminal neuropathic pain (TNP) and pain related to temporomandibular joint disorders (TMD). We here systematically reviewed the neuroimaging literature regarding the functional and structural changes in the brain of TNP and TMD pain patients, using a computerized search of journal articles via PubMed. Ten TNP studies and 14 TMD studies were reviewed. Study quality and risk of bias were assessed based on the criteria of patient selection, the history of medication, the use of standardized pain/psychological assessments, and the model and statistics of imaging analyses. Qualitative meta-analysis was performed by examining the brain regions which showed significant changes in either brain functions (including the blood-oxygen-level dependent signal, cerebral blood flow and the magnetic resonance spectroscopy signal) or brain structure (including gray matter and white matter anatomy). We hypothesized that the neuroimaging findings would display a common pattern as well as distinct patterns of brain signature in the disorders. This major hypothesis was supported by the following findings: (1) TNP and TMD patients showed consistent functional/structural changes in the thalamus and the primary somatosensory cortex, indicating the thalamocortical pathway as the major site of plasticity. (2) The TNP patients showed more alterations at the thalamocortical pathway, and the two disorders showed distinct patterns of thalamic and insular connectivity. Additionally, functional and structural changes were frequently reported in the prefrontal cortex and the basal ganglia, suggesting the role of cognitive modulation and reward processing in chronic orofacial pain. The findings highlight the potential for brain neuroimaging as an investigating tool for understanding chronic orofacial pain.

SUBMITTER: Lin CS

PROVIDER: S-EPMC3997345 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.

Lin Chia-Shu CS

PloS one 20140423 4

Brain neuroimaging has been widely used to investigate the bran signature of chronic orofacial pain, including trigeminal neuropathic pain (TNP) and pain related to temporomandibular joint disorders (TMD). We here systematically reviewed the neuroimaging literature regarding the functional and structural changes in the brain of TNP and TMD pain patients, using a computerized search of journal articles via PubMed. Ten TNP studies and 14 TMD studies were reviewed. Study quality and risk of bias we ...[more]

PMID: 24759798

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Project description:BackgroundPain due to temporomandibular disorders (TMDs) often has the same clinical symptoms and signs as other types of orofacial pain (OP). The possible presence of serious neurological and/or systemic organic pathologies makes differential diagnosis difficult, especially in early disease stages. In the present study, we performed a qualitative and quantitative electrophysiological evaluation of the neuromuscular responses of the trigeminal nervous system. Using the jaw jerk reflex (JJ) and the motor evoked potentials of the trigeminal roots ((b)R-MEPs) tests, we investigated the functional and organic responses of healthy subjects (control group) and patients with TMD symptoms (TMD group).MethodThirty-three patients with temporomandibular disorder (TMD) symptoms and 36 control subjects underwent two electromyographic (EMG) tests: the jaw jerk reflex test and the motor evoked potentials of the trigeminal roots test using bilateral electrical transcranial stimulation. The mean, standard deviation, median, minimum, and maximum values were computed for the EMG absolute values. The ratio between the EMG values obtained on each side was always computed with the reference side as the numerator. For the TMD group, this side was identified as the painful side (pain side), while for the control group this was taken as the non-preferred masticatory side (non-preferred side). The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were also calculated.ResultsAnalysis of the ratios (expressed as percentages) between the values obtained on both sides revealed a high degree of symmetry in the (b)R-MEPs % in the control (0.93 +/- 0.12%) and TMD (0.91 +/- 0.22%) groups. This symmetry indicated organic integrity of the trigeminal root motor fibers and correct electrode arrangement. A degree of asymmetry of the jaw jerk's amplitude between sides (ipJJ%), when the mandible was kept in the intercuspal position, was found in the TMD group (0.24% +/- 0.14%) with a statistically significant difference in relation to the control group (0.61% +/- 0.2%). This asymmetry seemed to be primarily due to a failure to facilitate the reflex on the painful side in intercuspal position.ConclusionsIn this 2 x 2 matrix diagnostic model, three different types of headache may be identified: 1) those due to organic pathologies directly and indirectly involving the trigeminal nervous system denoted as "Organic Damage"; 2) those in TMD patients; 3) other types of orofacial pain in subjects who could erroneously be considered healthy, denoted as Orofacial Pain "OP". This category of patient should be considered at risk, as organic neurological pathologies could be present and yet not directly affect the trigeminal system, at least in the early stages of the disease.

Project description:Trigeminal neuropathic pain is the most debilitating pain disorder but current treatments including opiates are not effective. A common symptom of trigeminal neuropathic pain is cold allodynia/hyperalgesia or cold hypersensitivity in orofacial area, a region where exposure to cooling temperatures are inevitable in daily life. Mechanisms underlying trigeminal neuropathic pain manifested with cold hypersensitivity are not fully understood. In this study, we investigated trigeminal neuropathic pain in male rats following infraorbital nerve chronic constrictive injury (ION-CCI). Assessed by the orofacial operant behavioral test, ION-CCI animals displayed orofacial cold hypersensitivity. The cold hypersensitivity was associated with the hyperexcitability of small-sized trigeminal ganglion (TG) neurons that innervated orofacial regions. Furthermore, ION-CCI resulted in a reduction of A-type voltage-gated K+ currents (IA currents) in these TG neurons. We further showed that these small-sized TG neurons expressed Kv4.3 voltage-gated K+ channels, and Kv4.3 expression in these cells was significantly downregulated following ION-CCI. Pharmacological inhibition of Kv4.3 channels with phrixotoxin-2 inhibited IA-currents in these TG neurons and induced orofacial cold hypersensitivity. On the other hand, pharmacological potentiation of Kv4.3 channels amplified IA currents in these TG neurons and alleviated orofacial cold hypersensitivity in ION-CCI rats. Collectively, Kv4.3 downregulation in nociceptive trigeminal afferent fibers may contribute to peripheral cold hypersensitivity following trigeminal nerve injury, and Kv4.3 activators may be clinically useful to alleviate trigeminal neuropathic pain.SIGNIFICANCE STATEMENT Trigeminal neuropathic pain, the most debilitating pain disorder, is often triggered and exacerbated by cooling temperatures. Here, we created infraorbital nerve chronic constrictive injury (ION-CCI) in rats, an animal model of trigeminal neuropathic pain to show that dysfunction of Kv4.3 voltage-gated K+ channels in nociceptive-like trigeminal ganglion (TG) neurons underlies the trigeminal neuropathic pain manifested with cold hypersensitivity in orofacial regions. Furthermore, we demonstrate that pharmacological potentiation of Kv4.3 channels can alleviate orofacial cold hypersensitivity in ION-CCI rats. Our results may have clinical implications in trigeminal neuropathic pain in human patients, and Kv4.3 channels may be an effective therapeutic target for this devastating pain disorder.

Project description:Introduction: Pain is an emotional experience. As a subjective feeling, it is associated with pathophysiological processes occurring in the central nervous system, which in turn may negatively affect the psychophysical function, cognitive abilities, level of functioning and quality of life. The Aim: The aim of the study was to assess orofacial and general pain location in patients with temporomandibular joint disorder-myofascial pain with referral. Materials and Methods: The study group consisted of 50 randomly selected, generally healthy people with complete natural dentition (37 women and 13 men) at the age of 23.36 ± 2.14 years, referred to the Department of Prosthodontics of the Medical University. All patients underwent clinical examination according to the Diagnostic Criteria for Temporomandibular Disorders (Axes I and II). The subjects were classified as people with myofascial pain with referral. The evaluation of severity of temporomandibular disorders was based on the Temporomandibular Disorder Pain Screener and the Graded Chronic Pain Scale. In order to assess orofacial and general pain location, a bodychart drawing of pain was used. Results: The study group indicated 40 different areas of the body affected by pain. 2-3 isolated pain locations were declared by a total of six subjects. One person identified 17 affected areas. Forty four people reported pain in at least four regions of the body. 70% of patients suffered from pain within the right masseter muscle. Pain of the left masseter muscle was noted in 68% of cases. Cervical ailments were reported by 56% of people. Pain of the left temporomandibular joint was observed in 68% of patients, and of the right one in 54%. Conclusion: The patients with myofascial pain with referral suffer from general ailments in different regions of the body. Only the frequency of pain in the right masseter muscle and right temporomandibular joint differed with respect to gender. The suggestion that the prevalence of pain in other areas of the body varies between men and women has not been confirmed. Due to a small sample size, such differences cannot be excluded. Further studies in this area are needed.

Dataset Information

Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.

Publications

Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.

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