Ko Dezawa

Interaction of IL-1β and P2X(3) receptor in pathologic masseter muscle pain.

The exact mechanism underlying chronic masseter muscle pain, a conspicuous symptom in temporomandibular disorder, remains unclear. We investigated whether expression of P2X3 receptor (P2X3R) is involved in mechanical hyperalgesia after contraction of masseter muscle (CMM). As compared with sham rats, the head-withdrawal threshold (HWT) to mechanical pressure stimulation of masseter muscle (MM) (but not after similar stimulation of facial skin) was significantly lower, and IL-1β level was significantly higher, in CMM rats on day 7 after CMM. The mean percentage of FG-labeled P2X3R-positive neurons was significantly increased in TG following successive IL-1β injections into the MM for 7 days. Successive administration of an IL-1β receptor-antagonist into the MM attenuated the increase of P2X3-IR cells in the TG. ATP release from MM after 300-g pressure stimulation of MM was also significantly enhanced after CMM. Administration into MM of the selective P2X3,2/3 receptor antagonist A-317491 attenuated the decrement of HWT in CMM rats. A significant increase in HWT was also observed at 30 min after A-317491 (60 µg) injection in IL-1β-injected rats. These findings suggest that P2X3R expression associated with enhanced IL-1β expression and ATP release in MM has a possible important role in MM mechanical hyperalgesia after excessive muscular contraction.

Efficacy of distortion correction on diffusion imaging: comparison of FSL eddy and eddy_correct using 30 and 60 directions diffusion encoding.

Diffusion imaging is a unique noninvasive tool to detect brain white matter trajectory and integrity in vivo. However, this technique suffers from spatial distortion and signal pileup or dropout originating from local susceptibility gradients and eddy currents. Although there are several methods to mitigate these problems, most techniques can be applicable either to susceptibility or eddy-current induced distortion alone with a few exceptions. The present study compared the correction efficiency of FSL tools, “eddy_correct” and the combination of “eddy” and “topup” in terms of diffusion-derived fractional anisotropy (FA). The brain diffusion images were acquired from 10 healthy subjects using 30 and 60 directions encoding schemes based on the electrostatic repulsive forces. For the 30 directions encoding, 2 sets of diffusion images were acquired with the same parameters, except for the phase-encode blips which had opposing polarities along the anteroposterior direction. For the 60 directions encoding, non–diffusion-weighted and diffusion-weighted images were obtained with forward phase-encoding blips and non–diffusion-weighted images with the same parameter, except for the phase-encode blips, which had opposing polarities. FA images without and with distortion correction were compared in a voxel-wise manner with tract-based spatial statistics. We showed that images corrected with eddy and topup possessed higher FA values than images uncorrected and corrected with eddy_correct with trilinear (FSL default setting) or spline interpolation in most white matter skeletons, using both encoding schemes. Furthermore, the 60 directions encoding scheme was superior as measured by increased FA values to the 30 directions encoding scheme, despite comparable acquisition time. This study supports the combination of eddy and topup as a superior correction tool in diffusion imaging rather than the eddy_correct tool, especially with trilinear interpolation, using 60 directions encoding scheme.

Stellate ganglion block as an early intervention in sympathetically maintained headache and orofacial pain Caused by Temporal Arteritis

INTRODUCTION We report a case of temporal arteritis with a sympathetic component in the orofacial region, which responded to stellate ganglion blocks (SGBs). CASE An 81-year-old woman with limited mouth opening and pain upon chewing was referred to the Orofacial Pain Clinic at Nihon University Dental Hospital. The patient also presented with blurred vision and a burning sensation on the right side of her face. On clinical examination, the temporal artery was tender to palpation, and there was increased sensitivity in the temporal region bilaterally. The patient reported jaw pain and limited mouth opening. Laboratory examination showed elevations in erythrocyte sedimentation rate and C-reactive protein. The burning sensation was due to a sympathetic component, and SGBs substantially reduced both the burning sensation and right temporal pain. Blocking the sympathetic chain on the ipsilateral side also improved jaw movement. The patient was referred to a rheumatologist, after which she was admitted to hospital with a tentative diagnosis of temporal arteritis. Treatment with oral prednisone 30 mg daily was initiated, and the dose was tapered as her symptoms resolved. DISCUSSION The reason for the gradual pain relief after SGB is unclear, but we believe it was effective for ischemia in temporal arteritis because it led to dilation of affected arteries or suppression of inflammation/edema of the vascular wall. CONCLUSION This case demonstrates that SGB may relieve pain related to temporal arteritis and sympathetically maintained headache and orofacial pain by reducing noxious stimulation peripherally and decreasing central pain transmission centrally.

Spatial and Temporal Brain Responses to Noxious Heat Thermal Stimuli in Burning Mouth Syndrome

Burning mouth syndrome (BMS) is an idiopathic orofacial pain condition. Although the pathophysiology of BMS is not clearly understood, central and peripheral neuropathic mechanisms are thought to be involved. The authors compared brain response to noxious heat stimuli in 16 right-handed women with primary BMS and 15 sex- and age-matched right-handed healthy female controls. A thermal stimulus sequence of 32 °C to 40 °C to 32 °C to 49 °C was repeated 4 times in a cycle. Warm and noxious heat stimuli were delivered with a Peltier thermode placed on the right palm or right lower lip for 32 s each in a session. Functional magnetic resonance imaging data were obtained by recording echoplanar images with a block design. Statistical Parametric Mapping 8 software was used to analyze the data. Patients and controls both reported feeling more pain during palm stimulation than during lip stimulation. Repetition of noxious heat stimulus on the lower lip but not on the palm induced habituation in brain activity in the cingulate cortex without reduction in pain perception. Multiple regression analysis revealed a correlation between perceived pain intensity and suppression of brain activity in the anterior cingulate cortex when the repeated thermal sequence was applied at the lower lip. Furthermore, the response of the parahippocampal area differed in BMS patients and controls when the same repeated thermal sequence was applied at the palm. The authors’ findings indicate that BMS patients show specific brain responses due to impaired function of the central and peripheral nervous systems (clinical trial registration: UMIN000015002).

p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats

BackgroundOrofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund’s adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain.ResultsMechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration.ConclusionsThese findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.

Headache attributed to temporomandibular disorders and masticatory myofascial pain

We investigated the temporal association between temporomandibular disorders (TMD)-related symptoms and headache during TMD treatment for patients who fulfilled the diagnostic criteria for headache attributed to TMD (HATMD) specified in the Diagnostic criteria for TMD (DC/TMD) and International classification of headache disorders (ICHD)-3 beta. The study enrolled 34 patients with HATMD induced by masticatory myofascial pain but not by temporomandibular arthralgia. Facial pain intensity, the pressure pain threshold of pericranial muscles, and maximum unassisted opening of the jaw were assessed at an initial examination and before and after physical therapy. The intensity and frequency of headache episodes and tooth contact ratio were also recorded before and after the intervention. Headache intensity and frequency significantly decreased, and these reductions were temporally related to improvements in facial pain intensity, maximum unassisted opening, and pressure pain threshold during TMD treatment. Linear regression analysis showed significant correlations between facial pain intensity and headache intensity and between tooth contact ratio and pressure pain threshold. Among patients who fulfilled the DC/TMD and ICHD-3 beta diagnostic criteria for HATMD, headache improved during TMD treatment, and the improvement was temporally related to amelioration of TMD symptoms. These findings suggest that sensitization in the central and peripheral nervous systems is responsible for HATMD. (J Oral Sci 58, 195-204, 2016).

Altered structural connectivity of pain-related brain network in burning mouth syndrome—investigation by graph analysis of probabilistic tractography

PurposeBurning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis.MethodsFourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity.ResultsIn BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed.ConclusionStructural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Short-term effects of orthognathic surgery on somatosensory function and recovery pattern in the early postoperative period.

We examined the short-term surgical effects of orthognathic surgery on somatosensory function. Observations were made over a short period: 3 months postoperatively. In total, 14 patients and 32 healthy controls participated. Among the 14 patients, one underwent bilateral sagittal split osteotomy alone and 13 underwent bilateral sagittal split osteotomy in combination with a Le Fort I osteotomy. A modified quantitative sensory testing (QST) protocol (the German Research Network on Neuropathic Pain, DFNS) was used to evaluate clinically the skin of the chin for sensory disturbances before surgery and at 1 week, 1 month, and 3 months postoperatively. A visual analog scale and the Japanese Version of the McGill Pain Questionnaire were completed by all participants. Both sides of the mandible showed postoperative functional loss in cold detection threshold, warmth detection threshold, thermal sensory limen, and mechanical detection threshold. All function gradually recovered to baseline conditions at 3 months postoperatively. Cold detection threshold, warmth detection threshold, thermal sensory limen, and mechanical detection threshold appeared to be useful QST parameters for evaluating neurosensory disturbances during the early postoperative period. (J Oral Sci 58, 177-184, 2016).

Micro-CT observation of in vivo temporal change in mandibular condyle morphology in BMAL1 knockout mice

Brain and muscle Arnt-like protein-1 (BMAL1) knockout mice exhibit accelerated aging, abnormal glucose metabolism, and impaired adipocyte differentiation, among other phenotypes, which are effects associated with the BMAL1 gene. No study has investigated temporal changes in the deformation of the mandibular condyle and the presence of calcification in areas surrounding the mandibular condyle. In a study of 12 C57/BL strain mice under inhalation anesthesia, we collected images of the mandibular condyle at 6 weeks after birth and then every 5 weeks from 10 to 25 weeks after birth. At 25 weeks, deformation of the mandibular condyle was seen in 8 of 12 joints in BMAL1 knockout mice and in 2 of 12 joints in wild-type mice. At 20 and 25 weeks, deformation in areas surrounding the mandibular condyle, which are known to undergo calcification, was seen in 2 of 12 joints in BMAL1 knockout mice and in 0 of 12 joints in wild-type mice. BMAL1 knockout mice exhibited premature aging of the mandibular condyle, which suggests that circadian rhythms affect mandibular condyle morphology.