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Objectives Patients after middle ear surgery often complain of taste disturbance and a lingual numbness. The purpose of this study was to objectively assess changes in the somatosensation of the tongue and taste function in patients undergoing stapes surgery. Study Design Prospective study. Methods Symptoms of taste disturbance and tongue numbness after surgery were investigated before and after surgery in 41 patients (13 males, 28 females; mean age 41.8 years) who underwent stapes surgery. Twenty-eight patients (9 males, 19 females; mean age 43.1 years) underwent sensory and taste function tests before and after surgery. Sensory function of the tongue was measured at the operated side and the nonoperated side using the 2-point discrimination test and an electrostimulator test. Taste function was assessed with electrogustometry (EGM). Results The chorda tympani nerve (CTN) was gently touched or stretched in all patients. Postoperative thresholds on the operated side were significantly higher than preoperative thresholds in all tests in the patients who underwent all three kinds of tests. Tongue somatosensory symptoms improved significantly earlier than the taste disturbance postoperatively, and the sensory thresholds returned to the baseline along with recovery of symptoms. Conclusion These findings suggest that dysfunction of the CTN occurred following surgery even when the CTN was preserved, and that the sensory nerve threshold of the tongue correlated with the symptom of lingual numbness. The CTN may play a role not only in taste function but also in the somatosensory function of the tongue. Level of Evidence 4. Laryngoscope, 2017

Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injury-induced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha. Conversely, intrathecal injection of the TLR3 agonist polyinosine-polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine-polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain.

Mitogen-activated protein kinase (MAPK) plays an important role in the induction and maintenance of neuropathic pain. Transforming growth factor-activated kinase 1 (TAK1), a member of the MAPK kinase kinase family, is indispensable for the activation of c-Jun N-terminal kinase (JNK) and p38 MAPK. We now show that TAK1 induced in spinal cord astrocytes is crucial for mechanical hypersensitivity after peripheral nerve injury. Nerve injury induced a striking increase in the expression of TAK1 in the ipsilateral dorsal horn, and TAK1 was increased in hyperactive astrocytes, but not in neurons or microglia. Intrathecal administration of TAK1 antisense oligodeoxynucleotide (AS-ODN) prevented and reversed nerve injury-induced mechanical, but not heat hypersensitivity. Furthermore, TAK1 AS-ODN suppressed the activation of JNK1, but not p38 MAPK, in spinal astrocytes. In contrast, there was no change in TAK1 expression in primary sensory neurons, and TAK1 AS-ODN did not attenuate the induction of transient receptor potential ion channel TRPV1 in sensory neurons. Taken together, these results demonstrate that TAK1 upregulation in spinal astrocytes has a substantial role in the development and maintenance of mechanical hypersensitivity through the JNK1 pathway. Thus, preventing the TAK1/JNK1 signaling cascade in astrocytes might provide a fruitful strategy for treating intractable neuropathic pain. © 2008 Wiley-Liss, Inc.

Heat and cold hyperalgesia is a common feature of inflammatory pain. To investigate whether activation of extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1, in primary sensory neurons participates in inflammatory pain, we examined the phosphorylation of ERK5 in the dorsal root ganglion (DRG) after peripheral inflammation. Inflammation induced by complete Freund's adjuvant produced heat and cold hyperalgesia on the ipsilateral hind paw and induced an increase in the phosphorylation of ERK5, mainly in tyrosine kinase A-expressing small- and medium-size neurons. In contrast, there was no change in ERK5 phosphorylation in the spinal dorsal horn. ERK5 antisense, but not mismatch, oligodeoxynucleotide decreased the activation of ERK5 and suppressed inflammation-induced heat and cold hyperalgesia. Furthermore, the inhibition of ERK5 blocked the induction of transient receptor potential channel TRPV1 and TRPA1 expression in DRG neurons after peripheral inflammation. Our results show that ERK5 activated in DRG neurons contribute to the development of inflammatory pain. Thus, blocking ERK5 signaling in sensory neurons that has the potential for preventing pain after inflammation.

Neuropathic pain that occurs after peripheral nerve injury is poorly controlled by current therapies. Increasing evidence shows that mitogen-activated protein kinase (MAPK) play an important role in the induction and maintenance of neuropathic pain. Here we show that activation of extracellular signal-regulated protein kinases 5 (ERK5), also known as big MAPK1, participates in pain hypersensitivity caused by nerve injury. Nerve injury increased ERK5 phosphorylation in spinal microglia and in both damaged and undamaged dorsal root ganglion (DRG) neurons. Antisense knockdown of ERK5 suppressed nerve injury-induced neuropathic pain and decreased microglial activation. Furthermore, inhibition of ERK5 blocked the induction of transient receptor potential channels and brain-derived neurotrophic factor expression in DRG neurons. Our results show that ERK5 activated in spinal microglia and DRG neurons contributes to the development of neuropathic pain. Thus, blocking ERK5 signaling in the spinal cord and primary afferents has potential for preventing pain after nerve damage.

Objective: Although many studies report short-term hearing results after surgically managing semicircular canal fistulae, long-term results are still unknown. In the present study, long-term postoperative hearing outcomes were reviewed in 14 ears of patients with cholesteatoma and semicircular canal fistulae.Method: Between 1996 and 2010, 84 patients with cholesteatoma and semicircular canal fistulae underwent tympanoplasty at Hyogo College of Medicine Hospital. The location of the fistula was the lateral semicircular canal in all cases and superior semicircular canal in 5 cases. Fourteen patients were followed up for more than 5 years.Results: Postoperative air-bone gap was ≤10 dB in 1 case, between 11 and 20 dB in 7 cases, between 21 and 30 dB in 4 cases, and ≥31 dB in 2 cases. Mean bone-conduction hearing levels on the operated side had deteriorated by 3 dB in 1 kHz, by −1 dB in 2 kHz, and −2 dB in 4 kHz at 1 year postoperatively and by 8 dB, 6 dB, and 2 dB at 5 years postoperatively, respectively. Bon...