Effect of the antirheumatic medication methotrexate (MTX) on biomechanical compressed human periodontal ligament fibroblasts (hPDLFs).

BACKGROUND: The aim of this study was to investigate the in vitro effect of the antirheumatic drug methotrexate (MTX) on biomechanically compressed human periodontal ligament fibroblasts (hPDLFs), focusing on the expression of interleukin 6 (IL-6), as its upregulation is relevant to orthodontic tooth movement. METHODS: Human PDLFs were subjected to pressure and simultaneously treated with MTX. Cell proliferation, viability and morphology were studied, as was the gene and protein expression of IL-6. RESULTS: Compared with that in untreated fibroblasts, IL-6 mRNA expression in mechanically compressed ligament fibroblasts was increased (two to sixfold; ****p < 0.0001). Under compression, hPDLFs exhibited a significantly more expanded shape with an increase of cell extensions. MTX with and without pressure did not affect IL-6 mRNA expression or the morphology of hPDLFs. CONCLUSION: MTX has no effect on IL-6 expression in compressed ligament fibroblasts.

Neurophysiological changes associated with implant placement.

OBJECTIVES: The objective of the study was to evaluate the feasibility of a standardized Quantitative Sensory Testing (QST) protocol extra- and intraoral in patients to detect and quantify sensory disturbances of the inferior alveolar nerve due to the proximity of implantation procedures to the inferior alveolar nerve canal. MATERIAL AND METHODS: Patients who had obtained an implant placement were examined by implementing a comprehensive QST protocol for extra- and intraoral use. The study included 33 patients after implant placement in the lower jaw and one patient suffering from an inferior alveolar nerve injury. Patients were tested bilaterally (chin and mucosal lower lip). RESULTS: Comparing the implanted vs. the control side, QST parameters revealed no significant neurophysiological changes in all parameters. Evaluating the development of sensory disturbances in dependency of the proximity of the implant to the inferior alveolar nerve canal, mechanical QST parameters showed no significant correlation. The mean distance of the inserted implant to the inferior nerve canal was 2.65 ± 1.75 mm. In the case of one patient suffering from impairment of the nerve function due to implant placement, we found abnormal sensory responses to touch coexisting with numbness and temperature algesia. CONCLUSIONS: Monitoring of trigeminal nerve fiber functions by QST intra- and extraoral is feasible to evaluate oral sensory pattern after implantation procedures. Sensory disturbances of the inferior alveolar nerve were shown to be avoided by keeping an average safety zone of 2.65 mm between implant and nerve.

Profiling intraoral neuropathic disturbances following lingual nerve injury and in burning mouth syndrome.

BACKGROUND: The aim of the study was to analyse intraoral neurophysiological changes in patients with unilateral lingual nerve lesions as well as patients with Burning Mouth Syndrome (BMS) by applying a standardized Quantitative Sensory Testing (QST) protocol. METHODS: The study included patients suffering from a peripheral lesion of the lingual nerve (n = 4), from BMS (n = 5) and healthy controls (n = 8). Neurophysiological tests were performed in the innervation areas of the tongue bilaterally. For BMS patients the dorsal foot area was used as reference. RESULTS: For patients with peripheral lesion of the lingual nerve the affected side of the tongue showed increased thresholds for thermal (p < 0.05-0.001) and mechanical (p < 0.01-0.001) QST parameters, indicating a hypoesthesia and thermal hypofunction. In BMS patients, a pinprick hypoalgesia (p < 0.001), a cold hyperalgesia (p < 0.01) and cold/warmth hypoesthesia (p < 0.01) could be detected. CONCLUSIONS: The results of this study verified the lingual nerve lesion in our patients as a peripheral dysfunction. The profile showed a loss of sensory function for small and large fibre mediated stimuli. A more differentiated classification of the lingual nerve injury was possible with QST, regarding profile, type and severity of the neurologic lesion. BMS could be seen as neuropathy with variable central and peripheral contributions among individuals resulting in chronic pain.

Brain connectivity networks underlying resting heart rate variability in acute ischemic stroke.

Acute strokes can affect heart rate variability (HRV), the mechanisms how are not well understood. We included 42 acute stroke patients (2-7 days after ischemic stroke, mean age 66 years, 16 women). For analysis of HRV, 20 matched controls (mean age 60.7, 10 women) were recruited. HRV was assessed at rest, in a supine position and individual breathing rhythmus for 5 min. The coefficient of variation (VC), the root mean square of successive differences (RMSSD), the powers of low (LF, 0.04-0.14 Hz) and high (HF, 0.15-0.50 Hz) frequency bands were extracted. HRV parameters were z-transformed related to age- and sex-matched normal subjects. Z-values < -1 indicate reduced HRV. Acute stroke lesions were marked on diffusion-weighted images employing MRIcroN and co-registered to a T1-weighted structural volume-dataset. Using independent component analysis (ICA), stroke lesions were related to HRV. Subsequently, we used the ICA-derived lesion pattern as a seed and estimated the connectivity between these brain regions and seven common functional networks, which were obtained from 50 age-matched healthy subjects (mean age 68.9, 27 women). Especially, LF and VC were frequently reduced in patients. ICA revealed one covarying lesion pattern for LF and one similar for VC, predominantly affecting the right hemisphere. Activity in brain areas corresponding to these lesions mainly impact on limbic (r = 0.55 ± 0.08) and salience ventral attention networks (0.61 ± 0.10) in the group with reduced LF power (z-score < -1), but on control and default mode networks in the group with physiological LF power (z-score > -1). No different connectivity could be found for the respective VC groups. Our results suggest that HRV alteration after acute stroke might be due to affecting resting-state brain networks.

Somatosensory and Gustatory Profiling in the Orofacial Region.

Quantitative sensory testing (QST) is a standard procedure in medicine to describe sensory patterns in various pathologies. The aim of this prospective clinical study was to define reference values of the trigeminal nerve (V3), including taste qualities, to create a compatibility for sensory loss or gain in pathologies. Fifty-one patients were included, and a standardized testing battery with 11 QST parameters according to the German Research Network on Neuropathic Pain (DFNS) was applied complemented by quantitative gustatory assessments. Significant somatosensory differences were found between the test sites (MDT at the chin, WDT at the lower lip) but no effect was detected for gender, age, and between body types. Taste sensitivity was dependent on concentration, gender (females being more sensitive) and increasing age (for bitter and sour taste). We provide reference values for somatosensory and gustatory testing of the facial area. Our data facilitate the detection of neurosensory abnormalities in the orofacial region. This might also serve as a control setting for COVID-19.

Neurophysiological changes and chronic pain in cleft patients.

The aim of this study was to evaluate if patients after orofacial cleft repair experience neurophysiological changes with consecutive chronic pain states after surgery. Patients (n = 48) with a repaired orofacial cleft (CLP) recruited in a support group took part in a survey including five questionnaires. They revealed pain states, described cleft situation and history, and epidemiological data. Patients' quality of life and psychological comorbidity after the surgical procedures were assessed with the Oral Health Impact Profile (OHIP), the Giessen Subjective Complaints List (GSCL) and the Hospital Anxiety and Depression Scale (HADS). Furthermore, psychosocial impairment was documented. 39 out of 48 subjects with CLP reported to have experienced pain during the last 6 months. Pain was proven to be already chronic for 36 persons. Locations of pain were the orofacial region, back and limbs. Neurophysiological perception to cold, warmth, pressure and touch were found to be inhomogeneous. Local disturbances of subjective sensitivity in hard and soft tissues in the operated region are suspicious for neuropathic disorders and peripheral and central sensitization. 16 participants also reported that during dental interventions higher doses of local analgesia were necessary to achieve a pain free condition. Overall participants with CLP demonstrated elevated levels for anxiety and depression. As a conclusion for daily routine, CLP patients are considered to be at a higher risk to develop chronic pain states. To avoid these, proper pain and psychological management must be performed from early childhood. Further clinical studies examining patients with neurophysiological diagnostic tools are needed.

Neurophysiological changes associated with implant-associated augmentation procedures in the lower jaw.

BACKGROUND: Neurophysiological changes after oral and maxillofacial surgery remain one of the topics of current research. PURPOSE: This study evaluated if implant placement associated with augmentation procedures increases the possibility of sensory disturbances or result in impaired quality of life during the healing period. MATERIAL AND METHODS: Patients who had obtained an implant placement in the lower jaw in combination with augmentation procedures were examined by implementing a comprehensive Quantitative Sensory Testing (QST) protocol for extra- and intraoral use. As augmentation procedures, we used Guided Bone Regeneration (Group A) and Customized Bone Regeneration (Group B) techniques. Patients were tested bilaterally at the chin and mucosal lower lip. Results were compared to a group without augmentation procedures (Group C). Patients' quality of life and psychological comorbidity after the surgical procedures was assessed with the Oral Health Impact Profile and the Hospital Anxiety and Depression Scale. RESULTS: For groups A (n = 20) and B (n = 8), mechanical QST parameters showed no significant differences in all qualities of the inferior alveolar nerve compared to the contralateral side and compared to the nonaugmentation control group (n = 32) as well. Evaluation of quality of life and psychological factors showed no statistical differences. CONCLUSIONS: Augmentation procedures did not increase sensory disturbances, indicating no changes in the neurophysiological pathways. Extended augmentation procedures did not lead to sensory changes either or result in an impaired quality of life or modified anxiety and depression scores.