Pulsed Radiofrequency of the Auriculotemporal Nerve to Reduce the Intensity of Tinnitus.

INTRODUCTION: Stimulation of the nonauditory nervous systems via the trigeminal nerve pathways can be a promising intervention for patients with tinnitus refractory to medical, conservative, and other treatment options. Therapy of the mandibular division of the trigeminal nerve through the auriculotemporal nerve has been reported as useful for patients with tinnitus. OBJECTIVES: The objective of our study was to study the long-term effects of pulsed radiofrequency of the auriculotemporal nerve in a large group of tinnitus sufferers and to find predictors for a prosperous result. DESIGN: A monocenter backward-looking group study. RESULTS: In a two-year period, 67 tinnitus patients had pulsed radiofrequency of the auriculotemporal nerve. Twentythree (35%) reported reduced tinnitus loudness at the 7-week post-treatment follow-up. These patients valued the improvements as: 61% good, 22% moderate, and 17% slight. In 3% of patients, tinnitus magnified after the treatment. The odds of permanent tinnitus relief after successful pulsed radiofrequency of the auriculotemporal nerve are 68% at 1 year postoperative. In tinnitus patients without cervical pain 62% had an improvement following pulsed radiofrequency of the auriculotemporal nerve compared to 28% in those not fulfilling this criterion (p=0.024). CONCLUSIONS: Neuromodulation of the auriculotemporal nerve is an uncomplicated remedy for tinnitus. In a select group of tinnitus patients this treatment can a good relief of their tinnitus for a long period. Especially, tinnitus sufferers without cervical pain will benefit of this therapy.

Pulsed Radiofrequency of the Auricular Branch of the Vagal Nerve in Tinnitus Patients.

INTRODUCTION: Pulsed radiofrequency of the auricular branch of the vagal nerve has strongly reduced tinnitus in a person with violent tinnitus and severe cervical pain. OBJECTIVES: The objective of our study was to study the long-term effects of pulsed radiofrequency of the auricular branch of the vagal nerve in a large group of tinnitus sufferers and to find predictors for a prosperous result. DESIGN: A monocenter backward-looking group study. RESULTS: 48% of tinnitus sufferers who undertook pulsed radiofrequency of the auricular branch of the vagal nerve reported a reduced loudness of their tinnitus, which was qualified as being moderate to good in 87% of these patients. The reduction exceeded mostly 1 year. An angle smaller than 3 degrees between the 2nd and 3rd cervical vertebrae on lateral radiograph predicted a better outcome of this therapy. CONCLUSION: Neuromodulation of the auricular branch of the vagal nerve is an uncomplicated remedy for tinnitus, especially for tinnitus patients with a pathologically small C2-C3 angle.

Pain in relationship to Tinnitus and Hearing Loss.

INTRODUCTION: Cervical and lower back pain are noteworthy in the manner of development of tinnitus. OBJECTIVES: The focus of this research was to indicate the consequence of the severity of neck pain and pain of the lower back and/or lower limbs in tinnitus patients. DESIGN: A retrospective analysis of 61 patients with tinnitus as main complaint during a three month period. RESULTS: In this study, we found two groups of tinnitus patients defined by the existence of postural instability. Patients with tinnitus and postural unsteadiness were characterized by predominant female, self-perceived hearing loss, a higher intensity of tinnitus, cervical pain, and pain of the lower back and/or of the lower limbs, and more hearing deficit from 250 Hz to 4 kHz. CONCLUSIONS: In patients with tinnitus one should be aware that hearing loss can be a consequence of high intensity cervical pain. Stimulation of the proprioceptive input pathways due to cervical pain can result in a higher intensity of tinnitus and a hearing loss in the range of 250 Hz to 4 kHz.

Pulsed Radiofrequency of the Vagal Nerve for Tinnitus -A Case-Study.

TINNITUS BACKGROUND: Vagal nerve stimulation is a promising therapy for tinnitus. Pulsed radiofrequency is a minimally invasive neuromodulator technique that could be applied repeatedly without damage to neural tissue. In this case-study we document the use of pulsed radiofrequency of the vagal nerve as a successful therapy without harm for patients with tinnitus. METHODS: A 22-gauge, 60 mm-long needle with a 5 mm active tip was placed percutaneously at the inner side of the tragus. The auricular branch of the vagal nerve was subjected to pulsed radiofrequency at 42 V, 2 Hz, and 10 milliseconds for 10 minutes. RESULTS: Pulsed radiofrequency of the vagal nerve can reduce tinnitus and improve hearing in a patient with severe tinnitus and hearing loss. The intensity of the tinnitus was reduced to 5% of the original intensity at the left side and to 20% at the right side. An improved hearing of 20 to 30 dB from 250 Hz to 8 kHz in the left ear and from 250 Hz to 2 kHz in the right ear was objectivated in the audiogram. CONCLUSIONS: This case-study document that PRF of the vagal nerve can reduce tinnitus and improve hearing in a patient with severe tinnitus and hearing loss. However, further research of PRF of the vagal nerve in tinnitus patients is needed.

Somatosensory-Auditory Processing of the Fifth Cervical Nerve in Tinnitus.

INTRODUCTION: Cervical spinal nerve projections influence auditory responses and play a role in the pathology of tinnitus. OBJECTIVES: The intention of our research was to lay down the amenity of treatment of the fifth (C5) cervical nerve to lessen tinnitus and to obtain specifications associated with a long-term effect of this method. DESIGN: Subjects were 54 tinnitus patients who were treated with infiltration of the fifth cervical nerve. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. RESULTS: Treating the C5 is beneficial for 30% of the tinnitus patients. The majority of patients with a beneficial result rated the tinnitus reduction of 50% or more. At 9 months, half of the patients still had benefit. Less hearing at 1 kHz together with a large spur in front of the fifth cervical vertebrae forecasted a beneficial effect of the C5 therapy on tinnitus at 7 weeks. CONCLUSIONS: Treating cervical spine complaints can lessen tinnitus. Therapy of C5 resulted in less tinnitus for 30% of the tinnitus patients. However, selection of tinnitus patients with an evident spur in front of the fifth cervical vertebrae together with a less hearing at 1 kHz will improve the success rate of C5 therapy.

Cervical Nerve Projections to the Auditory Pathway in Tinnitus.

INTRODUCTION: Cervical spinal nerves project to the auditory system and take part in the pathology of tinnitus. OBJECTIVES: The intention of our research was to estimate the outcome of treatment of C6 and C7 to lessen tinnitus intensity and to find criteria for a long-term success. DESIGN: Subjects were 78 tinnitus patients who were treated with infiltration of the sixth and seventh cervical nerve. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. RESULTS: In a cohort of tinnitus patients, 18% had less tinnitus after treatment of C6 and C7. The majority of the patients announced a moderate easing of their tinnitus. At 2,5 months, half of the patients with a positive response still had benefit. The combination of hearing loss at 8 kHz and the highness of the intervertebral disc at C4-C5 forecasted a beneficial result of therapy of C6 and C7 with a longer period of relief. CONCLUSIONS: Treating afferent cervical nerves can lessen tinnitus. Therapy of C6 and C7 caused less tinnitus for 18% of the tinnitus patients. Especially patients with no hearing loss at 8 kHz and no disc degeneration at C4-C5 forecasted a beneficial result of therapy of C6 and C7 on tinnitus with a longer period of relief.

Proprioception: the missing link in the pathogenesis of tinnitus?

OBJECTIVES: The object of this study was to relate cervical spine pathology to the occurrence of tinnitus and of cervical pain. DESIGN: A retrospective analysis of 124 patients with tinnitus as main complaint and 300 patients with cervical pain as main complaint who visited our clinic in a two-year period. RESULTS: In patients with tinnitus as main complaint, 64% of the patients have also cervical pain, and in patients with cervical pain as main complaint, 44% of the patients have tinnitus. Both groups of patients have in common a high prevalence of postural instability and dizziness, degeneration of the intervertebral disc between the fifth and seventh cervical vertebrae, and a large anterior spur in front of the fifth cervical vertebrae. Patients with cervical pain as main complaint have more degeneration of the intervertebral disc between the third and fourth cervical vertebrae, a larger anterior spur in front of the third cervical vertebrae and more loss of cervical lordosis. CONCLUSIONS: Postural instability is an important discriminant factor in patients with cervical pain and in patients with tinnitus as main complaint. In patients with cervical pain postural instability was associated with the occurrence of tinnitus. In patients with tinnitus, there is evidence for two profiles of somatic tinnitus, discriminated by the occurrence of postural instability and low-frequency hearing loss. It seems that the combination of tinnitus and postural instability begins as a cervical pain syndrome and that the tinnitus aggravates in time, possibly by the occurrence of hearing loss, internal diseases, or surgery of the lower limb.

Is Pain Harder To Withstand Than Tinnitus?

OBJECTIVES: The object of the study was to compare the perception of tinnitus with the perception of pain and to find specific factors that could influence the perception of both pain and tinnitus. DESIGN: A retrospective analysis of 124 patients with tinnitus as main complaint and 300 patients with cervical pain as main complaint who visited our clinic in a two-year period. RESULTS: This study indicates that it is harder to withstand cervical pain than tinnitus with a higher prevalence of fatigue and impaired work performance in cervical pain patients. Our analyses highlight the importance of fatigue as a potential mediator of the deleterious effects of pain and tinnitus on individual functioning. Female gender and the presence of cervical pain makes patients more accessible for fatigue. Tolerance against tinnitus depends on the perceived maximal intensity of tinnitus, but also of the presence of cervical pain. Cervical pain may reinforce the irritating awareness of tinnitus. CONCLUSION: Tinnitus and chronic pain are related to structural and functional brain changes that show a striking overlap between both conditions. The tolerance, the ability to withstand the "unpleasantness" of the percept, for tinnitus and pain depends on the perceived intensity of the sensation. However, the perceived intensity of pain provoked annoyance earlier compared to the perceived intensity of tinnitus. Cervical pain may reinforce and maintain the negative awareness of tinnitus. For a better withstanding of tinnitus, we advise to reduce the perceived maximal intensity of tinnitus and to treat cervical pain and fatigue.

Amplifiers in Tinnitus Patients.

INTRODUCTION: High tinnitus loudness can be provoked by peripheral disorders of the somatosensory and/or auditory system. OBJECTIVES: The object of our study was to compare high tinnitus loudness patients with low tinnitus loudness patients and to find specific factors associated with high tinnitus loudness. DESIGN: A retrospective cohort analysis of 234 patients with tinnitus as main complaint who visited our clinic in a four-year period. METHODS: Data obtained from the subjects were age, sex, the loudness of tinnitus estimated by the VAS, and the outcomes of the audiogram and the cervical spine radiograph. RESULTS: High tinnitus loudness was associated with a higher prevalence of females, more dizziness, less self-perceived hearing loss, more cervical disc degeneration at C3 to C6, and a larger anterior spur of cervical vertebrae C3 to C6. Females had a lower prevalence of tinnitus but a higher chance on high tinnitus loudness. Gender, the size of the largest anterior spur from C3 to C6, and the ratio of hearing loss at 8 kHz and hearing loss at 2 kHz are involved in the amplification of tinnitus loudness. CONCLUSIONS: High tinnitus loudness can be provoked by peripheral disorders of the somatosensory and/or auditory system. A steep audiometric edge between hearing at 2 kHz and hearing at 8 kHz and/or cervical spine pathology with sympathetic nervous system irritation can amplify tinnitus loudness causing high tinnitus loudness.

Upper Cervical Nerves Can Induce Tinnitus.

INTRODUCTION: Treating cervical spine disorders can result in a reduction of tinnitus. OBJECTIVES: The object of the study was to ascertain the benefit of therapy of the third and fourth cervical nerves in reducing tinnitus and to assess parameters indicating a long-term relief. DESIGN: Subjects were 37 tinnitus patients who were treated with infiltration of the third and fourth cervical nerves. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. RESULTS: In a group of tinnitus patients, 19% of the patients reported less tinnitus after therapy of the third and fourth cervical nerves. Most of the patients had a moderate reduction of 25% to 50%. At 3.8 months, 50% of the successful treated patients still had a positive effect. No adverse events of the procedure were observed. The combination of an evident anterior spur at the third cervical vertebrae together with less hearing at 2 kHz indicate patients who responded the best to therapy of the third and fourth cervical nerves. CONCLUSIONS: Treating cervical spine disorders can reduce tinnitus. In a group of tinnitus patients, 19% of the patients had less tinnitus after therapy of the C3 and C4. Screening of tinnitus patients is needed for the proper selection of the ones who could benefit from a somatic approach. In our study, the combination of an evident anterior spur at the third cervical vertebrae together with less hearing at 2 kHz indicate patients who responded the best following therapy of the C3 and C4.

The eight cervical nerve and its role in tinnitus.

INTRODUCTION: The eight cervical nerve might be a source of input to the auditory system. OBJECTIVES: The object was to assess the efficacy of infiltration of the eight cervical nerve root for treating tinnitus patients and to find indicators for a successful result. DESIGN: Retrospective cohort study. Subjects were 79 tinnitus patients visiting our clinic in a three-year period and who were treated with infiltration of the eight cervical nerve root. RESULTS: Twenty-six percent of the tinnitus patients had a reduction of their tinnitus following an infiltration of the eight cervical nerve root. Most of the successfully treated patients rated the effect of therapy as a moderate reduction of 25% to 50%. Fifty percent of the successful treated patients still had benefit at 6.6 months. In 5% of the patients, their tinnitus was aggravated after the infiltration of the eight cervical nerve roots. Patients with a hearing loss at 500 Hz that exceed the hearing loss at 2 kHZ responded the most to infiltration of the eight cervical nerve. CONCLUSION: Infiltration of the eight cervical nerve root reduced the intensity of tinnitus in 26% of the cohort of 79 tinnitus patients with a moderate to good effect. This therapy for tinnitus patients' needs to be considered, especially in those with a hearing loss at 500 Hz that exceed the hearing loss at 2 kHZ.

Sleep Disturbances Associated With Tinnitus: Reduce the Maximal Intensity of Tinnitus.

INTRODUCTION: The high prevalence together with the serious impact of sleep disturbances assessed in tinnitus patients urge the need for effective therapy that could improve patients' sleep quality. OBJECTIVES: The purpose of this study was to assess the reported prevalence and severity of sleep disturbance in chronic tinnitus patients and to extract possible tinnitus specific factors that increase the risk of developing sleep disturbances. DESIGN: Subjects were 165 consecutive patients who came to our clinic from January 2017 to January 2019 for consultations on their tinnitus that persisted for one month or longer. Patients charts, audiogram, and sleep questionnaire were reviewed retrospectively and data from these patients were recorded. RESULTS: Half of the tinnitus patients experienced a poor sleep quality. Cervical pain, the use of benzodiazepines and antidepressants, a higher maximal and a higher mean intensity of tinnitus were associated with a poor sleep quality. Especially, a higher maximal intensity of tinnitus was associated with a poor sleep quality. With a VAS of the maximal intensity of the tinnitus higher than 85 millimeter, 69% of the patients have a poor sleep quality. If the VAS of the maximal intensity of the tinnitus was less than 60 millimeter, none of the patients had a poor sleep quality. CONCLUSIONS: In a cohort of patients with chronic tinnitus, we found that half of the tinnitus patients experienced poor sleep quality. The level of the maximal intensity of tinnitus was associated with the sleep quality. It seems that reduction of the intensity of the tinnitus is essential for improvement of quality and patients' quality of life in patients with tinnitus.

Psychosocial consequences of the loudness of tinnitus.

INTRODUCTION: Tinnitus distress is associated with the perceived loudness of the tinnitus. OBJECTIVES: To evaluate the psychosocial problems in tinnitus patients and to explore any relation with the tinnitus loudness. DESIGN: From all patients who were treated in our clinic from January 2017 to September 2019 for their tinnitus, patients chart and a questionnaire with the psychosocial variables were studied retrospectively. RESULTS: Almost half of the tinnitus patients could not withstand their tinnitus and they were faced with disturbed concentration and feeling depressed. Psychosocial problems were related to the maximal loudness of the tinnitus. If the perceived maximal loudness of the tinnitus was above 73 millimetre on the visual analogue scale the prevalence of psychosocial problems raised. If it was above 83 millimetre the majority of these patients had psychosocial problems. CONCLUSION: Psychosocial problems were related to the maximal loudness of the tinnitus. We recommend patients suffering from severe tinnitus distress that therapy should be aimed at a reduction of the maximal loudness of tinnitus to less than 73 mm on the visual analogue scale.

Pulsed radiofrequency of C2 dorsal root ganglion in patients with tinnitus.

INTRODUCTION: The second cervical nerve ganglion bar appears to be beneficial in patients with treatment safe tinnitus. As far as anyone is concerned, the viability of this methodology in patients with tinnitus has never been evaluated. OBJECTIVES: The point of this investigation was to decide the adequacy of beat radiofrequency of C2 dorsal root ganglion for treating patients with tinnitus, and all the more explicitly, to survey the parameters related with a long haul advantage so as to improve understanding determination. DESIGN: Subjects were 61 back to back patients who went to our facility from October 2016 to October 2018 for discussions on their tinnitus that endured for one month or more and were treated with beat radiofrequency of C2 dorsal root ganglion. Clinical information structure these patients were explored reflectively. An autonomous spectator assesses the long haul impact of the treatment by phone meet. RESULTS: In a partner of patients with tinnitus that persevered for one month or more, 25% of the patients reacted with a decrease of their tinnitus after a beat radiofrequency of C2 dorsal root ganglion. The vast majority of the patients with a positive reaction appraised the impact of treatment as a decrease of half or more. At 13.5 months, half of at first effective treated patients still encountered an advantage. Unfavorable occasions of the beat radiofrequency of C2 dorsal root ganglion at 7 weeks of follow-up were an expansion of the force of the tinnitus in 7% of the patients. In patients with an age under 43 years at the time tinnitus began, 45% of them had a decrease of their tinnitus at 7 weeks following treatment with beat radiofrequency of C2 dorsal root ganglion. CONCLUSION: Pulsed radiofrequency of C2 dorsal root ganglion can lessen the power of tinnitus extensively and for the long haul in 25% of the patients with tinnitus without genuine antagonistic impacts. We prescribe this treatment in patients with an age under 43 years at the time tinnitus began.

Percutaneous Radiofrequency Lesion of the Superior Cervical Sympathetic Ganglion in Patients with Tinnitus.

OBJECTIVE: The aim of this study was to determine the efficacy of radiofrequency lesioning of the superior cervical sympathetic ganglion for patients with tinnitus. STUDY DESIGN: This is a retrospective long-term clinical review of patients with tinnitus treated with a blockade of the superior cervical sympathetic ganglion. SETTING: The human subjects were 366 consecutive patients who came to the DC Klinieken in Almere and Amsterdam from January 2010 to January 2014 for consultations on their tinnitus that persisted for 1 month or longer. SUBJECTS AND METHODS: Data were recorded from patients whose charts were reviewed retrospectively to identify the patients who were treated with a blockade of the superior cervical sympathetic ganglion for tinnitus. An independent observer conducted a long-term follow-up assessment of the therapy by telephone interview. RESULTS: Relief of tinnitus at 7-week follow-up was achieved in 64% of the patients treated with a radiofrequency lesion of the superior cervical sympathetic ganglion after a positive test blockade of this structure. Two years after the treatment, the maintenance of a tinnitus relief occurred in almost 40% of the patients with a follow-up period of two years or longer. CONCLUSIONS: A radiofrequency lesion of the superior cervical sympathetic ganglion may be a useful alternative for patients with tinnitus not responding to conventional therapy.

Protocadherin-1 binds to SMAD3 and suppresses TGF-ß1-induced gene transcription.

Genetic studies have identified Protocadherin-1 (PCDH1) and Mothers against decapentaplegic homolog-3 (SMAD3) as susceptibility genes for asthma. PCDH1 is expressed in bronchial epithelial cells and has been found to interact with SMAD3 in yeast two-hybrid (Y2H) overexpression assays. Here, we test whether PCDH1 and SMAD3 interact at endogenous protein levels in bronchial epithelial cells and evaluate the consequences thereof for transforming growth factor-ß1 (TGF-ß1)-induced gene transcription. We performed Y2H screens and coimmunoprecipitation (co-IP) experiments of PCDH1 and SMAD3 in HEK293T and 16HBE14o(-) (16HBE) cell lines. Activity of a SMAD3-driven luciferase reporter gene in response to TGF-ß1 was measured in BEAS-2B cells transfected with PCDH1 and in 16HBE cells transfected with PCDH1-small-interfering RNA (siRNA). TGF-ß1-induced gene expression was quantified in BEAS-2B clones overexpressing PCDH1 and in human primary bronchial epithelial cells (PBECs) transfected with PCDH1-siRNA. We confirm PCDH1 and SMAD3 interactions by Y2H and by co-IP in HEK293T cells overexpressing both proteins, and at endogenous protein levels in 16HBE cells. TGF-ß-induced activation of a SMAD3-driven reporter was reduced by exogenous PCDH1 in BEAS2B cells, whereas it was increased by siRNA-mediated knockdown of endogenous PCDH1 in 16HBE cells. Overexpression of PCDH1 suppressed expression of TGF-ß target genes in BEAS-2B cells, whereas knockdown of PCDH1 in human PBECs increased TGF-ß-induced gene expression. In conclusion, we demonstrate that PCDH1 binds to SMAD3 and regulates its activation by TGF-ß signaling in bronchial epithelial cells. We propose that PCDH1 and SMAD3 act in a single pathway in asthma susceptibility that affects sensitivity of the airway epithelium to TGF-ß.

Reduced effect of percutaneous retrogasserian glycerol rhizolysis in trigeminal neuralgia affecting the third branch.

INTRODUCTION: The objective of this study was to determine the long-term efficacy of percutaneous glycerol rhizolysis of the trigeminal ganglion for treating patients with trigeminal neuralgia and search for predictors associated with (long-term) benefit to improve patient selection. METHODS: A retrospective study in 60 consecutive patients treated with percutaneous glycerol rhizolysis of the trigeminal ganglion for trigeminal neuralgia. Charts were reviewed in combination with follow-up by questionnaire (n = 55, 92% response). RESULTS: Initial pain relief was achieved in 92% of the patients. Pain-free survival was 59% of the patients at 12 months and 53% at 24 months. Most common side effects were hypesthesia (15%), dry eye (5%), and meningitis (2%). In patients without involvement of the third branch of the trigeminal nerve, the initial effect was 79%, of which 90% achieved more than 2 years pain-free survival, compared with 97% initial effect and less than 40% pain-free survival of more than 2 years when the third trigeminal branch was involved. DISCUSSION: The present study demonstrates that involvement of the third branch is a negative predictor for long-term outcome in percutaneous glycerol rhizolysis of the trigeminal ganglion in patients with classical trigeminal neuralgia. However, in the absence of third-branch involvement, glycerol rhizolysis yields excellent long-term results when initial positive effect is obtained.

Relationship between Sensory Stimulation and Side Effects in Percutaneous Radiofrequency Treatment of the Trigeminal Ganglion.

INTRODUCTION: The objective of this study was to determine the efficacy of percutaneous radiofrequency (RF) treatment of the trigeminal ganglion for treating patients with trigeminal neuralgia, to determine which patients have a long-term benefit, and to evaluate the effect of RF parameters. METHODS: A retrospective study in 28 consecutive patients in combination with a follow-up questionnaire (n = 26, 93% response). RESULTS: An initial treatment effect of 89% was observed, 60% sustained at 12-month follow-up. Major side effects were hypesthesia (56%), dry eye (20%), and masseter muscle weakness (12%). A lower sensory stimulation threshold during treatment was associated with better patient satisfaction (P = 0.016), improved pain relief (P = 0.039), and trended toward more hypesthesia (P = 0.077). DISCUSSION: This low-volume study reported treatment effects in an older population that were similar to previous studies. Only a higher incidence of hypesthesia was detected by long-term follow-up. This study supported the high efficiency of RF treatment, but there was a high level of side effects. Most notable, low sensory stimulation was associated with increased hypesthesia, whereas higher stimulation levels yielded less effectiveness. Further investigation of an optimal sensory stimulation range for percutaneous RF treatment of the trigeminal ganglion was found to be warranted.

Characterization of protocadherin-1 expression in primary bronchial epithelial cells: association with epithelial cell differentiation.

Protocadherin-1 (PCDH1) is a novel susceptibility gene for asthma that is expressed in airway epithelium. We aimed to characterize PCDH1 mRNA transcripts and protein expression in primary bronchial epithelial cells and to determine regulation of PCDH1 during mucociliary differentiation. Total RNA and protein were isolated from human primary bronchial epithelial cells. PCDH1 transcripts were characterized by rapid amplification of cDNA ends in bronchial epithelial cells of 4 subjects. PCDH1 expression was quantified by quantitative RT-PCR and Western blotting in bronchial epithelial cells directly ex vivo and after air liquid interface (ALI) or submerged culture. We identified 5 novel exons on the 5' end and 1 exon on the 3' end of PCDH1. Novel transcripts showed major variation in expression of intracellular conserved motifs. Expression levels of PCDH1 transcripts encoding exon 1-2 were 4-fold higher, and transcripts encoding exon 3-4 were 15-fold higher in freshly isolated bronchial epithelial cells than in submerged cultures. PCDH1 mRNA (3- to 8-fold) and protein levels (2- to 3-fold) were strongly up-regulated during mucociliary differentiation of primary bronchial epithelial cells in ALI cultures. In summary, PCDH1 transcripts display remarkable variability in expression of conserved intracellular signaling domains. Enhanced PCDH1 expression levels strongly correlate with differentiation of bronchial epithelial cells.

Tibial Nerve Block as Treatment of Chronic Foot Pain.

Background: Minimally invasive therapies can alleviate pain and improve walking in individuals with persistent foot and ankle pain. Objectives: The current study aimed to define the protracted consequences of tibial nerve blocks with steroids for individuals with persistent foot pain and to investigate the link between the thermography of the plantar foot and the beneficial effect of a tibial nerve block with steroids. Methods: All patients with chronic foot pain (n = 45) in this cohort underwent a block of the tibial nerve in the Department of Pain Therapy of Pain Clinic De Bilt, Utrecht, Netherlands, within November 2019 to April 2020. The thermographic images of patients were taken before and after injection. Results were retrospectively evaluated after 18 months. Results: In this study, 53% of the patients had pain relief at 7 weeks of follow-up with a unilateral or bilateral block of the tibial nerve. An improvement in walking distance was reported by 22% of the patients. Side effects of the tibial nerve block reported at 7 weeks of follow-up increased pain (5%) and the occurrence of leg cramps (5%) among the treated patients. At 18 months, 45% of the successfully treated feet still had benefits. A difference between the big toe's temperature and the foot's average temperature of less than -0.9°C on thermography before and after the tibial nerve block can predict a beneficial result of therapy. Conclusions: Tibial nerve block provides a safe, minimally invasive treatment option for almost half of the patients with painful feet in this cohort, and when successful, it can last a long term. Thermographic imaging of the plantar foot can predict only to a small extent the beneficial effect of the tibial nerve block with steroids on foot pain. Tibial nerve block should be considered when custom foot orthoses have been inadequate for pain relief or restricted walking distance.