Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem.

Sneezing is a vital respiratory reflex frequently associated with allergic rhinitis and viral respiratory infections. However, its neural circuit remains largely unknown. A sneeze-evoking region was discovered in both cat and human brainstems, corresponding anatomically to the central recipient zone of nasal sensory neurons. Therefore, we hypothesized that a neuronal population postsynaptic to nasal sensory neurons mediates sneezing in this region. By screening major presynaptic neurotransmitters/neuropeptides released by nasal sensory neurons, we found that neuromedin B (NMB) peptide is essential for signaling sneezing. Ablation of NMB-sensitive postsynaptic neurons in the sneeze-evoking region or deficiency in NMB receptor abolished the sneezing reflex. Remarkably, NMB-sensitive neurons further project to the caudal ventral respiratory group (cVRG). Chemical activation of NMB-sensitive neurons elicits action potentials in cVRG neurons and leads to sneezing behavior. Our study delineates a peptidergic pathway mediating sneezing, providing molecular insights into the sneezing reflex arc.

Considerations and Management of a Laryngeal Fracture after Sneezing.

Non-traumatic laryngeal fracture is uncommon but should be suspected whenever patients present with dysphonia, odynophagia, dysphagia, neck crepitus, or hemoptysis following a sneeze or coughing episode. Physical examination coupled with computed tomography is essential for making the diagnosis. Management can vary depending on the severity of the case, but the general approach is similar to any trauma. In this report, we describe a non-traumatic laryngeal fracture that occurred following a forceful sneeze. The case was notable for the presence of pneumomediastinum, independent mobility of the thyroid ala, and operative intervention was pursued to repair the fracture.

Remedia Sternutatoria over the Centuries: TRP Mediation.

Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants.

Transformative Approach To Investigate the Microphysical Factors Influencing Airborne Transmission of Pathogens.

Emerging outbreaks of airborne pathogenic infections worldwide, such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, have raised the need to understand parameters affecting the airborne survival of microbes in order to develop measures for effective infection control. We report a novel experimental strategy, TAMBAS (tandem approach for microphysical and biological assessment of airborne microorganism survival), to explore the synergistic interactions between the physicochemical and biological processes that impact airborne microbe survival in aerosol droplets. This innovative approach provides a unique and detailed understanding of the processes taking place from aerosol droplet generation through to equilibration and viability decay in the local environment, elucidating decay mechanisms not previously described. The impact of evaporation kinetics, solute hygroscopicity and concentration, particle morphology, and equilibrium particle size on airborne survival are reported, using Escherichia coli MRE162 as a benchmark system. For this system, we report that (i) particle crystallization does not directly impact microbe longevity, (ii) bacteria act as crystallization nuclei during droplet drying and equilibration, and (iii) the kinetics of size and compositional change appear to have a larger effect on microbe longevity than the equilibrium solute concentration.IMPORTANCE A transformative approach to identify the physicochemical processes that impact the biological decay rates of bacteria in aerosol droplets is described. It is shown that the evaporation process and changes in the phase and morphology of the aerosol particle during evaporation impact microorganism viability. The equilibrium droplet size was found to affect airborne bacterial viability. Furthermore, the presence of Escherichia coli MRE162 in a droplet does not affect aerosol growth/evaporation but influences the dynamic behavior of the aerosol by processing the culture medium prior to aerosolization, affecting the hygroscopicity of the culture medium; this highlights the importance of the inorganic and organic chemical composition within the aerosolized droplets that impact hygroscopicity. Bacteria also act as crystallization nuclei. The novel approach and data have implications for increased mechanistic understanding of aerosol survival and infectivity in bioaerosol studies spanning the medical, veterinary, farming, and agricultural fields, including the role of microorganisms in atmospheric processing and cloud formation.

Effects of a selective androgen receptor modulator (SARM), GSK2849466A, on stress urinary incontinence and bladder activity in rats with ovariectomy-induced oestrogen deficiency.

OBJECTIVES: To report the effect of a selective androgen receptor modulators (SARMs) on the urethral continence mechanisms in a rat model of stress urinary incontinence (SUI) induced by bilateral ovariectomy (OVX). MATERIALS AND METHODS: Female Sprague-Dawley rats with bilateral OVX were used. Rats were divided into five groups; sham operated, vehicle-treated OVX, low-dose SARM-treated OVX (GSK2849466A: 0.005 mg/kg/day, per os [p.o.]), high-dose SARM-treated OVX (GSK2849466A: 0.03 mg/kg/day, p.o.) and dihydrotestosterone (DHT)-treated OVX (1 mg/kg/day, subcutaneous) groups. After 4 weeks of SARM treatments or 3 weeks of DHT treatment (6 weeks after OVX), rats were subjected to evaluation of the sneeze-induced continence reflex using microtransducer-tipped catheter methods, sneeze-induced leak-point pressure, and continuous cystometry measurements, followed by histological analyses of urethral tissues. RESULTS: (i) OVX significantly impaired urethral continence function after 6 weeks to induce SUI during sneezing. (ii) Low-dose SARM treatment restored urethral baseline pressure (UBP) without affecting the amplitude of urethral response during sneezing (A-URS), partially reversing OVX-induced SUI during sneezing. (iii) High-dose SARM treatment reversed decreases in both UBP and A-URS, more effectively preventing SUI during sneezing. (iv) DHT treatment only restored A-URS without affecting UBP, partially preventing OVX-induced SUI during sneezing. (v) The high-dose SARM treatment induced hypertrophy of the striated and smooth muscle around the urethra. (vi) SARM treatment did not affect bladder function in sham or OVX rats. CONCLUSION: Treatment with SARMs could be a more effective modality for the treatment of SUI than DHT, without affecting bladder function, by enhancing smooth- and striated muscle-mediated urethral function under stress conditions such as sneezing.

Sneeze and pop: a ruptured varicocele; analysis of literature, guided by a well-documented case-report.

BACKGROUND: An acute scrotal hematoma, secondary to a spontaneous rupture of a varicocele is still a rare presentation in daily practice. However, multiple case reports have been reported. Sudden increase in abdominal pressure, resulting to an increased venous pressure can lead to a rupture of the varicocele. Literature search shows that due to uncertainty of the diagnosis, explorative surgery is often performed, sometimes resulting in unnecessary orchiectomies. The objective of this study was to determine classical clinical presentation of patients with a spontaneous rupture of a varicocele, determine the diagnostic procedure, and give an insight in the follow-up. CASE PRESENTATION: We present a case of a 24-year old male with acute scrotal swelling after sneezing. Subsequently, we carried out a systematic literature search to identify all eligible studies to determine classic clinical presentation of spontaneous ruptures of a varicocele. CONCLUSION: The literature search shows that clinical presentation of idiopathic spontaneous scrotal hematomas is similar to testicular torsion, epididymo-orchitis, malignancy, or (incarcerated) inguinal hernia making differential diagnosis difficult. Especially when there has been increased abdominal pressure or strenuous activity preceding the symptoms, and the swelling is left sided, it should be included in the differential diagnosis for patient with acute inguinoscrotal swelling. Colour Doppler-Ultrasonography is recommended to distinguish between other causes of acute scrotum. The hematoma is usual self-limiting, justifying conservative treatment. Early surgical intervention is indicated with signs of ischaemia due to obstruction, infection of the hematoma, or uncertain diagnosis (i.e. malignancy). However, physicians should be cautious with direct exploration, as it led to unnecessary orchiectomy in 25% of patients. The hematoma can increase in size up to 3 months post-event, and it can take up to 15 months to completely resolve.

Sneezing in Primary Headaches With Cranial Autonomic Symptoms: Pathophysiological Considerations. A Series of Case Reports.

OBJECTIVE: To report a case series of sneezing systematically occurring in two cases with migraine and cranial autonomic symptoms and two with cluster headache. BACKGROUND: Sneezing occurring systematically during cluster headache or migraine is a rare condition. Sneezing has been described as a specific trigger for migraine. METHODS: Case reports. CASE SERIES: We describe four patients with primary headaches, presenting systematic sneezing at a definite time of premonitory, postdromal, or headache phase. All of these headaches were associated with cranial autonomic symptoms. CONCLUSION: Sneezing is a symptom associated with primary headaches. The definite place of sneezing in these patients suggests a particular implication of hypothalamus in the pathophysiology of these cases.

High luteinizing hormone weakens urinary continence mechanisms in association with prostaglandin E2 elevation in a postmenopausal rat model.

AIMS: To explore the role of luteinizing hormone (LH) in the urinary continence mechanism, urethral function was investigated using a postmenopausal rat model with high serum LH concentrations and the postmenopausal rat model given a gonadotropin releasing hormone (GnRH) antagonist to lower LH concentrations. METHODS: Adult female rats were divided into: 1) sham group; 2) ovariectomy group (OVX) with removal of bilateral ovaries; 3) OVX and GnRH-antagonist administered group (OVX + G); and 4) sham and GnRH-antagonist administered group (Sham + G). Urethral function was evaluated by the sneeze-induced urethral continence reflex experiment, and serum LH and prostaglandin E2 (PGE2) concentrations were measured. RESULTS: In the sneeze-induced urethral continence reflex experiment, urethral baseline pressure (UBP) and the amplitude of the urethral response during sneezing (A-URS) were measured. The UBP was significantly decreased in the OVX group than in the other groups. A-URS was significantly lower in the OVX group than in the Sham group, but with no significant difference compared with the OVX + G group. Lowering the serum LH by a GnRH-antagonist improved UBP to the same level as in the Sham group. The serum PGE2 concentration was significantly higher in the OVX group than in the other groups. CONCLUSIONS: The results suggested that the increased serum LH concentration in the OVX rat model worsened the continence mechanism. This mechanism is probably associated with an increased PGE2 concentration, because PGE2 caused urethral smooth muscle relaxation. A GnRH-antagonist might improve urinary incontinence by decreasing the serum LH and PGE2 concentrations.

Spontaneous pneumocephalus and subdural hemorrhage after sneezing.

Spontaneous pneumocephalus is defined as the presence of air in the absence of intracranial factors. The management of spontaneous pneumocephalus can be conservative or surgical, and surgical intervention could be urgently required if clinical deterioration is rapid. Here, we report a case of pneumocephalus and subdural hemorrhage after sneezing. A 24-year-old male reported to our emergency department with a chief complaint of headache and dizziness. The patient gave a history of onset of headache and dizziness after 2 episodes of heavy sneezing. There was neither a history of recent traumatic episode or previous surgery, nor any signs and symptoms of recent fever or upper respiratory tract infections. Physical examination showed no specific findings. Computed tomography was performed, which showed subdural hemorrhage and PNC in the left occipital lobe, left hemomastoid, and maxillary hemosinus. A neurosurgeon was consulted, who suggested admission in the intensive care unit. An otolaryngologist was then consulted for the left ear otorrhea and hearing impairment. Otoscopic examination showed hemotympanum of the left ear, for which pain control and conservative treatment was suggested. The patient was transferred to general ward 4 days later, since the following brain computed tomography showed resolution of the hemorrhage, and discharged 6 days later because of the improved signs and symptoms. Pneumocephalus and intracranial hemorrhage can occur without a history of trauma or surgery. Special attention is required if headache, dizziness, or other neurologic signs and symptoms occur immediately after sneezing. Intracranial hemorrhage and penumocephalus should be considered in the differential diagnosis.

Effects of multiple simulated birth traumas on urethral continence function in rats.

Multiple vaginal parities have been reported to be an important risk factor for stress urinary incontinence (SUI). Simulated birth trauma with single vaginal distention (VD) has been used to induce the SUI condition in animals; however, the effect of multiple simulated birth traumas on the urethral continence function has not been well characterized. Therefore, we examined the effects of multiple VDs on urethral functions in vivo and the changes in gene expressions of several molecules in the urethra using female SD rats, which were divided into three groups; sham, VD-1 (single VD), and VD-3 groups (3 times of VDs every 2 wk). Two weeks after the final VD, leak point pressure (LPP) and urethral responses during sneezing were evaluated. Also, changes in mRNA levels of urethral molecules were quantified with RT-PCR.　The VD-1 group did not show any change in LPP with only a tendency of decrease in amplitudes of the urethral responses during sneezing (A-URS); however, the VD-3 group showed a significant decrease in LPP and urethral responses such as baseline urethral pressure and A-URS accompanied with SUI episodes during sneezing. Nicotinic receptor subtypes and transforming growth factor (TGF)-ß1 were significantly increased in both VD-1 and VD-3 groups while TNF receptor (TNFR)-1, IL-6, collagens, and matrix metalloproteinases-9 were significantly increased only in the VD-3 group.　These data indicate that rats with multiple simulated birth traumas exhibit profound impairment of the urethral continence function and that these functional changes are associated with those in cytokines, extracellular matrix molecules, and nicotinic receptor subtypes in the urethra.

The effect of ovariectomy on urethral continence mechanisms during sneeze reflex in middle-aged versus young adult rats.

AIMS: Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. METHODS: Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. RESULTS: In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa. CONCLUSIONS: These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI.

A diagnostic study in patients with sciatica establishing the importance of localization of worsening of pain during coughing, sneezing and straining to assess nerve root compression on MRI.

PURPOSE: To test whether the localization of worsening of pain during coughing, sneezing and straining matters in the assessment of lumbosacral nerve root compression or disc herniation on MRI. METHODS: Recently the diagnostic accuracy of history items to assess disc herniation or nerve root compression on magnetic resonance imaging (MRI) was investigated. A total of 395 adult patients with severe sciatica of 6-12 weeks duration were included in this study. The question regarding the influence of coughing, sneezing and straining on the intensity of pain could be answered on a 4 point scale: no worsening of pain, worsening of back pain, worsening of leg pain, worsening of back and leg pain. Diagnostic odds ratio's (DORs) were calculated for the various dichotomization options. RESULTS: The DOR changed into significant values when the answer option was more narrowed to worsening of leg pain. The highest DOR was observed for the answer option 'worsening of leg pain' with a DOR of 2.28 (95 % CI 1.28-4.04) for the presence of nerve root compression and a DOR of 2.50 (95 % CI 1.27-4.90) for the presence of a herniated disc on MRI. CONCLUSIONS: Worsening of leg pain during coughing, sneezing or straining has a significant diagnostic value for the presence of nerve root compression and disc herniation on MRI in patients with sciatica. This study also highlights the importance of the formulation of answer options in history taking.

Comparison of the levels of infectious virus in respirable aerosols exhaled by ferrets infected with influenza viruses exhibiting diverse transmissibility phenotypes.

Influenza viruses pose a major public health burden to communities around the world by causing respiratory infections that can be highly contagious and spread rapidly through the population. Despite extensive research on influenza viruses, the modes of transmission occurring most often among humans are not entirely clear. Contributing to this knowledge gap is the lack of an understanding of the levels of infectious virus present in respirable aerosols exhaled from infected hosts. Here, we used the ferret model to evaluate aerosol shedding patterns and measure the amount of infectious virus present in exhaled respirable aerosols. By comparing these parameters among a panel of human and avian influenza viruses exhibiting diverse respiratory droplet transmission efficiencies, we are able to report that ferrets infected by highly transmissible influenza viruses exhale a greater number of aerosol particles and more infectious virus within respirable aerosols than ferrets infected by influenza viruses that do not readily transmit. Our findings improve our understanding of the ferret transmission model and provide support for the potential for influenza virus aerosol transmission.

Inhibitory role of the spinal cholinergic system in the control of urethral continence reflex during sneezing in rats.

AIMS: The urethral continence reflex during stress conditions such as sneezing or coughing is an important mechanism preventing stress urinary incontinence (SUI). Although the spinal noradrenergic and serotonergic pathways are known to modulate this reflex activity, the role of spinal cholinergic pathways in the control of urethral continence reflex has not been elucidated. We therefore investigated the effect of intrathecal administration of an acetylcholine esterase (AChE) inhibitor, which increases ACh in synaptic terminals, and anti-cholinergic agents on the sneeze-induced urethral reflex in rats. METHODS: Female SD rats were anesthetized with urethane. Urethral function was evaluated during sneezing induced by insertion of the rat whisker into the nostril. Effects of an AChE inhibitor, neostigmine, and muscarinic or nicotinic receptor antagonists administered at the level of L6-S1 spinal cord were examined. RESULTS: Neostigmine dose-dependently and significantly decreased the amplitude of urethral responses during sneezing (A-URS) with an approximately 70% reduction at 3 nmol, without changing urethral baseline pressure. The neostigmine-induced decrease in A-URS was significantly reversed by pretreatment with atropine (nonselective muscarinic receptor antagonist), methoctramine (M2 receptor antagonist) or 4-DAMP (M3 receptor antagonist), but not with pirenzepine (M1 receptor antagonist), tropicamide (M4 receptor antagonist), or mecamylamine (nicotinic receptor antagonist). CONCLUSIONS: These results indicate that an increase in endogenous ACh in the lumbosacral spinal cord inhibits the sneeze-induced urethral continence reflex via activation of M2 and/or M3-muscarinic receptors, implying the inhibitory role of spinal cholinergic pathways in the control of urethral continence reflex under stress conditions such as sneezing.

Spontaneous spinal epidural hematoma after abrupt sneezing with prompt recovery of severe paraparesis.

Spontaneous spinal epidural hematoma (SSEH) is a rare neurologic condition with threatening consequences when spinal cord compression is present. The diagnosis must be performed quickly using magnetic resonance imaging (MRI), which shows collection of blood in the epidural space. With spinal cord compression, there is an indication for urgent surgical decompression. Here, we present a 64-year-old woman who developed sudden thoracic and lower back pain accompanied by severe paraparesis and urinary retention after sneezing abruptly. An MRI revealed a posterior thoracic epidural hematoma extending from the T6 to T11 vertebral level with spinal cord compression. Decompression was recommended, but the patient refused surgery, while neurologically improving with time. Complete neurologic recovery was observed within 24 hours after SSEH onset. A conservative therapeutic approach with careful observation may therefore be considered as a treatment of choice in some cases where surgery is refused, (due to high risk or other reasons) and neurologic recovery is early and sustained.

[Sneezing as a mechanical defence - a numerical simulation and analysis of the nasal flow]. / Niesen als mechanische Abwehr - Numerische Simulation mit Analyse der durchströmten Nasenbereiche.

INTRODUCTION: The nose is responsible for humidification, heating and cleaning of the inhaled air. The sneeze reflex leads to a shock-like cleaning of the nose in strong particle exposure. The aim of this study was the simulation of intranasal air flow of sneezing in a realistic computer model. MATERIALS AND METHODS: Based on the CT scan of a 40 year old man a three-dimensional computer model of the nasal cavity and the ethmoid sinuses was created. Flow simulations were performed for different inspiratory and expiratory velocities (± 2 m/s to ± 45 m/s) in order to simulate sneezing. RESULTS were visualized and analyzed by video simulation. RESULTS: During inspiration the main airflow takes place along the middle turbinate. During expiration, the flow is located more cranially. This effect is caused by the shape of the nasopharynx and the posterior portions of the nasal turbinates. During very high speeds (sneezing) also adjacent ethmoid sinuses and the olfactory region are covered by the shock-like expiratory flow. A large vortex formation in the nasopharynx is responsible for a uniform distribution of the airflow also on lower nasal areas. CONCLUSION: Sneezing is a protective reflex that provides for cleaning of the nose. From a flow rate of 10 m/s, the cranial nasal areas as well as adjacent ethmoid sinuses are covered by the -airflow. Compared to the inspiratory airflow the exhalation is not just vice versa. Particles that deposed in the cranial nasal areas during quiet breathing are removed.

Implication of photic sneeze reflex in ophthalmology.

Background: Photic sneeze reflex (PSR) also known as autosomal dominant compelling helioophthalmic outburst is a rare condition characterized by uncontrolled sneezing in response to bright light. The exact mechanism causing this is poorly understood. However, various hypotheses have been proposed. Ophthalmic examination involves exposing the patient to bright light like slit lamp, indirect ophthalmoscopy, and surgical microscope, which can trigger sneezing in PSR patients. Purpose: The purpose of this video is to draw light to this rare phenomenon and its implication in ophthalmic surgery. Synopsis: A 74-year-old male patient presented with diminution of vision in left eye. On routine slit lamp and IDO examination, patient had repeated sneezing. We diagnosed him to have photic sneeze reflex. He had pseudophakic bullous keratopathy in the right eye and senile immature cataract in the left eye. Taking into consideration his one eyed status and PSR, measures were taken accordingly and cataract surgery was performed uneventfully. We describe in this video the challenges encountered with this phenomenon and approach in such cases. Highlights: In this video, we tried to give an idea about photic sneeze reflex and its theories. Also, we tried to bring out the impact of PSR on ophthalmologic practice. Video link: https://youtu.be/KMZ_PC0hzhI.

Paroxysmal sneezing after hypothalamic deep brain stimulation for cluster headache.

BACKGROUND: Cluster headache (CH) is the most common of the trigeminal autonomic cephalalgias (TAC), presenting with excruciatingly severe, short-lasting, unilateral headache accompanied by cranial autonomic symptoms. Chronic CH occurs in 10-15% of patients. Deep brain stimulation in the posterior hypothalamic region (hDBS) is successful in treating about 60% of patients otherwise refractory to medical treatment. CASE: A 28-year-old man had hDBS for medically refractory left-sided chronic CH, with a resultant reduction in frequency and severity of his attacks. He developed recurrent paroxysms of sneezing soon after the stimulation was started that have reduced after increasing the pulse width from 60 to 90 µs. DISCUSSION: Stimulation of the brain in the region of the posterior hypothalamus could produce sneezing from activation of facial nerve parasympathetic or trigeminal afferent pathway activation through the trigeminohypothalamic tract, or through other central mechanisms. DBS in general offers the opportunity to illuminate our understanding of brain function and for CH offers particular opportunities to understand a devastating primary headache syndrome.