The Role of Balloon Sinuplasty in the Treatment of Vacuum Rhinogenic Headache.

In this study we tried to demonstrate how balloon sinuplasty could be an option in the treatment of the Rhinogenic Headache due to a probably disventilation of frontal sinus recess. 107 patients were included in the study with diagnosis of Rhinogenic Headache. The surgical group underwent bilateral balloon sinuplasty of the frontal sinus. The medical group underwent pharmacological treatment. Headaches characteristics were evaluated by a clinical personal diary. The severity was recorded by Visual Analog Scale 4 and 8 months after treatment. 98 out of 107 patients completed the protocol. In surgical group and in medical one the mean headache score improved at four and eight months follow up. The headache frequency attacks per month decrease from a preoperative frequency of 18 (±4 SD) in surgical group and 17 (±3 SD) in medical group to 3 (±1 SD) and 6 (±3 SD) respectively at 4 months control but increased slightly to 5 (±2 SD) and 12 (±4 SD) after 8 months. We concluded that the balloon sinuplasty should be considered as an effective alternative option after an accurate selection of surgical candidates. However, it is important a 6-8 month follow-up to evaluate the efficacy and stability of the treatment used.

Sensitivity and specificity of vestibular bed-side examination in detecting VIII cranial nerve schwannoma with sensorineural sudden unilateral hearing loss as presenting symptom.

The objectives of this study were to identify signs of vestibular nerve suffering through a bedside vestibular examination protocol in case of sudden sensorineural unilateral hearing loss without spontaneous signs of vestibular impairment and to propose a bed-side vestibular examination based protocol for the focused execution of gadolinium-enhanced magnetic resonance imaging (MRI) only if a vestibular schwannoma is suspected. 96 patients, 52 men, 44 women, mean age 57.73 +/- 12.85 years, suffering from sudden sensorineural unilateral hearing loss, which presented neither vertigo nor spontaneous nystagmus, were enrolled. Pure tone audiometry, tympanometry, measurement of acoustic reflexes and Anderson test to detect adaptation, bedside vestibular examination through head shaking test, vibration test, head impulse test, hyperventilation test and detection of nystagmus in supine and lateral decubitus to search for signs of vestibular impairment were performed. Patients with signs of vestibular impairment and pure tone audiometry threshold at high frequencies better than 70 dB nHL were subjected to auditory brainstem responses. Gadolinium enhanced MRI centred on internal acoustic canals was carried out in all patients with sudden sensorineural unilateral hearing loss. Main outcome measures were signs of vestibular impairment at vestibular bedside examination and presence of vestibular schwannoma on MRI. Signs of vestibular impairment were detected in 22/96 cases (22.9%); a vestibular schwannoma was detected by MRI in 5/96 cases (5.2%), always when vestibular impairment was present. In case of sudden sensorineural unilateral hearing loss, vestibular bedside examination seems to be useful to restrict the suspicion of a vestibular schwannoma to cases with signs of vestibular impairment, reducing the number of MRI exams, with considerable economic savings.

Sensations and regional brain responses evoked by tussive stimulation of the airways.

Stimuli that evoke cough in humans also elicit a sensation described as the urge-to-cough. This sensation is perceived at levels of stimulation below the threshold for coughing and increases in intensity in response to higher levels of stimulation. Cough in humans can be consciously modified in intensity or suppressed altogether, and the urge-to-cough is likely to contribute to discretionary responses to tussive stimulation. Converging evidence from animal and human experiments have identified a widely distributed network of brain regions that are implicated in the representation of urge-to-cough and the control of coughing. This network incorporates regions that show responses associated with urge-to-cough ratings, such as limbic and somatosensory cortices, as well as paralimbic and premotor regions implicated in response inhibition that activate in association with efforts to suppress cough. The urge-to-cough can be influenced by psychological factors and preliminary findings suggest that these effects could be mediated by top-down influences. There is considerable impetus to understand circuits involved in the modulation of urge-to-cough because it may be possible to antagonise the troubling sensation while preserving the critical cough reflex.

Anterior canal BPPV and apogeotropic posterior canal BPPV: two rare forms of vertical canalolithiasis.

Posterior canal benign paroxysmal positional vertigo (BPPV) is the most frequent form of BPPV. It is characterized by a paroxysmal positioning nystagmus evoked through Dix-Hallpike and Semont positioning tests. Anterior canal BPPV (AC) is more rare than posterior canal BPPV; it presents a prevalent down beating positioning nystagmus, with a torsional component clockwise for the left canal, counterclockwise for the right canal. Due to the possible lack of the torsional component, it is sometimes difficult to identify the affected ear. An apogeotropic variant of posterior BPPV (APC) has recently been described, characterised by a paroxysmal positional nystagmus in the opposite direction to the one evoked in posterior canal BPPV: the linear component is down-beating, the torsional component is clockwise for the right canal, counter-clockwise for the left canal, so that a contra-lateral anterior canal BPPV could be simulated. During a 16 month period, of 934 BPPV patients observed, the authors identified 23 (2.5%) cases of apogeotropic posterior canal BPPV and 11 (1.2%) cases of anterior canal BPPV, diagnosed using the specific oculomotor patterns described in the literature. Anterior canal BPPV was treated with the repositioning manoeuvre proposed by Yacovino, which does not require identification of the affected side, whereas apogeotropic posterior canal BPPV was treated with the Quick Liberatory Rotation manoeuvre for the typical posterior canal BPPV, since in the Dix-Hallpike position otoliths are in the same position if they come either from the ampullary arm or from the non-ampullary arm. The direct resolution of BPPV (one step therapy) was obtained in 12/34 patients, 8/23 patients with APC and 4/11 patients with AC; canalar conversion into typical posterior canal BPPV, later treated through Quick Liberatory Rotation (two-step therapy), was obtained in 19 patients,14/23 with APC and 5/11 with AC. Three patients were lost to follow-up. Considering the effects of therapeutic manoeuvres, the authors propose a grading system for diagnosis of AC and APC: "certain" when a canalar conversion in ipsilateral typical posterior canal BPPV is obtained; "probable" when APC or AC are directly resolved; "possible" when disease is not resolved and cerebral neuroimaging is negative for neurological diseases. Our results show that the oculomotor patterns proposed in the literature are effective in diagnosing APC and AC, and that APC is more frequent than AC. Both of these rare forms of vertical canal BPPV can be treated effectively with liberatory manoeuvres.

Direction-fixed paroxysmal nystagmus lateral canal benign paroxysmal positioning vertigo (BPPV): another form of lateral canalolithiasis.

Benign paroxysmal positioning vertigo (BPPV) is the most frequent vertiginous syndrome. It is caused either by free-floating otoliths in the semicircular canals (canalolithiasis) or by otoconial debris adhering to a canal cupula (cupulolithiasis). The posterior canal is the most frequently involved (80%), while the lateral canal is involved less frequently (15%), and the rarest conditions are anterior canalolithiasis and apogeotropic posterior canalolithiasis (5%). The main diagnostic sign of lateral canal BPPV is paroxysmal horizontal bidirectional positioning nystagmus evoked through Pagnini-McClure's test (head roll in the yaw plane in supine position). In the geotropic variant, which is more frequent, the fast phase of the nystagmus is directed towards the lowermost ear, when the patient lies on the affected side or on the healthy side; in the apogeotropic variant, which is less frequent, the fast phase is directed always toward the uppermost ear, regardless of which side the patient lies on. Paroxysmal nystagmus is more intense on the affected side in the geotropic form, and more intense on the healthy side in the apogeotropic form. The authors describe five cases of another primitive and rare form of lateral BPPV, defined as "direction-fixed paroxysmal nystagmus lateral canal BPPV", which has previously been described by other authors as a transitory step observed during the transformation from an apogeotropic into a geotropic form. It is characterized by typical BPPV symptoms and diagnosed by the presence of a paroxysmal horizontal unidirectional positioning nystagmus, evoked through Pagnini-McClure's test, which is apogeotropic on the affected side and geotropic on the healthy side. In the reported cases, direction-fixed horizontal paroxysmal nystagmus was always transformed into a typical geotropic form. The clinical features and pathophysiology of direction-fixed nystagmus lateral canal BPPV are discussed.

Transneuronal tracing of airways-related sensory circuitry using herpes simplex virus 1, strain H129.

Sensory input from the airways to suprapontine brain regions contributes to respiratory sensations and the regulation of respiratory function. However, relatively little is known about the central organization of this higher brain circuitry. We exploited the properties of the H129 strain of herpes simplex virus 1 (HSV-1) to perform anterograde transneuronal tracing of the central projections of airway afferent nerve pathways. The extrathoracic trachea in Sprague-Dawley rats was inoculated with HSV-1 H129, and tissues along the neuraxis were processed for HSV-1 immunoreactivity. H129 infection appeared in the vagal sensory ganglia within 24 h and the number of infected cells peaked at 72 h. Brainstem nuclei, including the nucleus of the solitary tract and trigeminal sensory nuclei were infected within 48 h, and within 96 h infected cells were evident within the pons (lateral and medial parabrachial nuclei), thalamus (ventral posteromedial, ventral posterolateral, submedius, and reticular nuclei), hypothalamus (paraventricular and lateral nuclei), subthalamus (zona incerta), and amygdala (central and anterior amygdala area). At later times H129 was detected in cortical forebrain regions including the insular, orbital, cingulate, and somatosensory cortices. Vagotomy significantly reduced the number of infected cells within vagal sensory nuclei in the brainstem, confirming the main pathway of viral transport is through the vagus nerves. Sympathetic postganglionic neurons in the stellate and superior cervical ganglia were infected by 72 h, however, there was no evidence for retrograde transynaptic movement of the virus in sympathetic pathways in the central nervous system (CNS). These data demonstrate the organization of key structures within the CNS that receive afferent projections from the extrathoracic airways that likely play a role in the perception of airway sensations.

Functional taping applied to upper limb of children with hemiplegic cerebral palsy: a pilot study.

Functional taping with elastic bandages and adhesive tapes could limit the action of upper limb spastic muscles and sustain that of weaker muscles in children with hemiplegic cerebral palsy (CP). 16 young children with CP (3±2 years old) were enrolled in this pilot study including 5 months of taping in conjunction with conventional physical therapy, followed by 7 months of physical therapy alone (taping wash-out), and other 5 months of taping plus therapy. Large improvements in the Melbourne assessment score were found in the first period in which taping was used (+15.4%, p<0.001) and also in the second one despite 8 drop-outs (+8.4%, p=0.012), but not during the taping wash-out (- 4.6%; p=0.093). These results suggest that children with CP could benefit from the continuous correction provided by taping in order to limit the development of improper upper limb motor schemas and to favour that of proper ones.

Predictive role of nasal functionality tests in the evaluation of patients before nocturnal polysomnographic recording.

Obstructive sleep apnoea syndrome is a disease characterized by a collapse of the pharyngeal airway resulting in repeated episodes of airflow cessation, oxygen desaturation, and sleep disruption. It is a common disorder affecting at least 2-4% of the adult population. The role of nasal resistance in the pathogenesis of sleep disordered breathing and sleep apnoea has not been completely clarified. Aim of the present study was to establish whether nasal resistance and nasal volumes, measured by means of Active Anterior Rhinomanometry and Acoustic Rhinometry together with Muco-Ciliary Transport time play a positive predictive role in the evaluation of Obstructive sleep apnoea syndrome patients before running a nocturnal polysomnographic recording. A retrospective study was performed analysing 223 patients referred for suspected Obstructive sleep apnoea syndrome. All patients were submitted to complete otorhinolaryngological evaluation and underwent nocturnal polysomnography. On the basis of polysomnographic data analysis, the apnoea-hypopnoea index and snoring index, patients were classified into two groups: Group 1 (110/223 patients) with a diagnosis of mild-moderate Obstructive sleep apnoea syndrome (apnoea-hypopnoea index < 30) and Group 2 (113/223 patients) affected by snoring without associated hypoxaemia/hypercapnia. A control group of 76 subjects, not complaining of sleep disorders and free from nasal symptoms was also selected. The results showed, in all the snoring and Obstructive sleep apnoea syndrome patients, total nasal resistance and increased Muco-Ciliary Transport time compared to standard values. Furthermore, the apnoea-hypopnoea index was significantly higher in patients with higher nasal resistence and significantly different between the groups. These results allow us to propose the simultaneous evaluation of nasal functions by Active Anterior Rhinomanometry, Acoustic Rhinometry, and Muco-Ciliary Transport time in the selection of patients undergoing polysomnography.

Hyperventilation-induced nystagmus in a large series of vestibular patients.

The Hyperventilation Test is widely used in the "bed-side examination" of vestibular patients. It can either activate a latent nystagmus in central or peripheral vestibular diseases or it can interact with a spontaneous nystagmus, by reducing it or increasing it. Aims of this study were to determine the incidence, patterns and temporal characteristics of Hyperventilation-induced nystagmus in patients suffering from vestibular diseases, as well as its contribution to the differential diagnosis between vestibular neuritis and neuroma of the 8(th) cranial nerve, and its behaviour in some central vestibular diseases. The present study includes 1202 patients featuring, at vestibular examination, at least one sign of vestibular system disorders or patients diagnosed with a "Migraine-related vertigo" or "Chronic subjective dizziness". The overall incidence of Hyperventilation-induced nystagmus was 21.9%. It was detected more frequently in retrocochlear vestibular diseases rather than in end-organ vestibular diseases: 5.3% in Paroxysmal Positional Vertigo, 37.1% in Menière's disease, 37.6% in compensated vestibular neuritis, 77.2% in acute vestibular neuritis and 91.7% in neuroma of the 8(th) cranial nerve. In acute vestibular neuritis, three HVIN patterns were observed: Paretic pattern: temporary enhancement of the spontaneous nystagmus; Excitatory pattern: temporary inhibition of the spontaneous nystagmus; Strong excitatory pattern: temporary inversion of the spontaneous nystagmus. Excitatory patterns proved to be time-dependent in that they disappeared and were replaced by the paretic pattern over a period of maximum 18 days since the beginning of the disorder. In acoustic neuroma, Hyperventilation-induced nystagmus was frequently observed (91.7%), either in the form of an excitatory pattern (fast phases towards the affected site) or in the form of a paretic pattern (fast phases towards the healthy side). The direction of the nystagmus is only partially related to tumour size, whereas other mechanisms, such as demyelination or a break in nerve fibres, might have an important role in triggering the situation. Hyperventilation-induced nystagmus has frequently been detected in cases of demyelinating diseases and in cerebellar diseases: in multiple sclerosis, hyperventilation inhibits a central type of spontaneous nystagmus or evokes nystagmus in 75% of patients; in cerebellar diseases, hyperventilation evokes or enhances a central spontaneous nystagmus in 72.7% of patients. In conclusion the Hyperventilation Test can provide patterns of oculomotor responses that indicate a diagnostic investigation through cerebral magnetic resonance imaging enhanced by gadolinium, upon suspicion of neuroma of the 8(th) cranial nerve or of a central disease. In our opinion, however, Hyperventilation-induced nystagmus always needs to be viewed within the more general context of a complete examination of the vestibular and acoustic system.

Early subclinical cochlear dysfunction in myotonic dystrophy type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant inherited disorder clinically characterized by variable systemic manifestations. Among clinical features of the disease, 'precocious presbyacusis' has been previously reported. The underlying mechanism of this auditory impairment remains still poorly understood. Hearing is an active process located in the cochlea, where the outer hair cells (OHCs) play an important role in sound perception through a 'contractile' like movement resembling skeletal muscle fibers dynamics. OHCs status has not yet been investigated in DM1 patients. OHCs integrity can be assessed by measuring transient-evoked otoacoustic emissions (TEOAE), a non-invasive, repeatable, and objective quantitative tool. METHODS: We recruited 25 patients with a genetically confirmed diagnosis of DM1, and 28 age-matched control subjects. All of them underwent a routine audiological evaluation and TEOAE recordings. RESULTS: We detected a high prevalence of sensorineural high-frequency hearing loss (HFHL) in DM1 patients, significantly different if compared to control subjects. Interestingly, the accurate analysis of DM1 recorded data showed a marked impairment of TEOAE both in HFHL+ and unexpectedly in HFHL- group. Cochlear dysfunction was restricted to frequencies above 2000 Hz in the HFHL- group, but it extended to 1000 Hz in HFHL+ DM1 patients. CONCLUSIONS: Our study indicates that cochlear impairment in DM1 is present, even in patients without evidence of hearing loss at a standard audiometric analysis. Hence, in the current clinical practice, an assessment of cochlear function by TEOAE recording may be useful in DM1 patients to identify precocious signs of cochlear dysfunction.

"Secondary signs of lateralization" in apogeotropic lateral canalolithiasis.

The diagnosis of lateral canalolithiasis is based on the typical finding of the horizontal paroxysmal positional nystagmus induced by the Pagnini-Mc Clure manoeuvre. This technique usually identifies also the affected side, namely, the side where the paroxysmal nystagmus is more intense in geotropic forms and the side where the paroxysmal nystagmus is less intense in apogeotropic forms. However, this method is not always applicable since, especially in apogeotropic forms, the intensity of the nystagmus is not so distinctly different between the two sides. Further useful signs to identify the affected side have been described in the Literature: Pseudo-spontaneous nystagmus in the sitting position; Leaning and Bowing nystagmus; Null-point in the vertical plane; Sitting to supine positioning nystagmus; Null-point in the horizontal plane. They are fully explained at pathophysiological level by the mechanism of canalolithiasis, as they are caused by otoliths moving in the ampullopetal direction in the non-ampullary segment (geotropic canalolithiasis) of the lateral canal or in ampullofugal direction in the ampullary segment (apogeotropic canalolithiasis) of the lateral canal. In other words, the movement of otoliths determines excitatory or inhibitory endolymphatic flow that generates specific nystagmic eye-movements. Authors analyse the characteristics of these signs, that they define as "Secondary signs of lateralization", in 64 cases of apogeotropic lateral canalolithiasis. A decisive contribution of the "Secondary signs of lateralization" to diagnose the pathological side has been verified in 13 out of 64 cases, whereas, in all other cases, Pagnini-Mc Clure diagnostic manoeuvre proved successful in correctly identifying the affected side by itself. Among the "Secondary signs of lateralization", the Pseudo-spontaneous nystagmus in the sitting position and the Sitting to the supine positioning nystagmus were particularly useful, due to both their frequency and their easy detection, as they do not require additional manoeuvres besides those usually performed during health examination of a patient affected by lateral canalolithiasis. In conclusion, the Authors propose a decision-making algorithm to diagnose and treat lateral canalolithiasis based on the attempt to obtain as much information as possible for a correct diagnosis, with the least trouble and inconvenience for patients.

Cough sensors. V. Pharmacological modulation of cough sensors.

Several airway afferent nerve subtypes have been implicated in coughing. These include bronchopulmonary C-fibers, rapidly adapting airway mechanoreceptors and touch-sensitive tracheal Adelta-fibers (also called cough receptors). Although the last two afferent nerve subtypes are primarily sensitive to mechanical stimuli, all can be acted upon by one or more different chemical stimuli. In this review we catalogue the chemical agents that stimulate and/or modulate the activity of the airway afferent nerves involved in cough, and describe the specific mechanisms involved in these effects. In addition, we describe the mechanisms of action of a number of chemical inhibitors of these afferent nerve subtypes, and attempt to relate this information to the regulation of coughing in health and disease.

The first case of osteoma in the false vocal fold.

OBJECTIVES: This article reports the first evidence of a larynx osteoma of the false vocal fold. STUDY DESIGN: Case report and literature review. METHODS: Case report and review of previously published cases of larynx osteomas. RESULTS: A 79-year-old patient was referred to our institution for dysphagia and hoarseness. Fibrolaryngoscopy showed a regular surface tumefaction of the false fold and the left ventricle, with preserved cordal motility. Patient underwent direct laryngoscopy with CO(2) laser excision of the lesion. Pathologic examination of the lesion (1.6cmx1cm) showed features consistent with an osteoma. Complete regression of symptoms was observed after surgery, with no lesions found on routine 1-year follow-up. CONCLUSIONS: Osteomas are benign, slow growing tumors of the craniofacial bone area, very rarely located in the larynx. Although the etiology is unknown, accepted theories point to embryologic, post-traumatic and infectious causes. Surgical excision is indicated only in symptomatic cases. This case report is the fourth evidence of laryngeal osteoma and, to our knowledge, the first finding of a false vocal fold osteoma.

Converting apogeotropic into geotropic lateral canalolithiasis by head-pitching manoeuvre in the sitting position.

Liberatory treatment of lateral canalolithiasis is more effective for the geotropic, than for the apogeotropic forms and, therefore, it is worthwhile attempting to convert the apogeotropic forms into the geotropic forms. In 36 cases of apogeotropic lateral canalolithiasis, one to five Head-Pitch Manoeuvres were performed in the sitting position (Head-Pitch Test) in the attempt to transform apogeotropic into geotropic lateral canalolithiasis. The Head Pitch Test was performed by a quick 60 degrees forward-flexion and a slow maximal backward-extension of the head. The Head-Pitch Test was effective in 36.1% of cases, less than the repeated Head-Rolling in the supine position, but it was always well tolerated by patients. The quick 60 degrees forward-flexion of the head can evoke a horizontal nystagmus beating towards the healthy side in apogeotropic lateral canalolithiasis and towards the affected side in geotropic lateral canalolithiasis (Bow Nystagmus). Slow backward-extension of the head can evoke a horizontal nystagmus beating towards the affected side in apogeotropic lateral canalolithiasis and toward the healthy side in geotropic lateral canalolithiasis (Lean Nystagmus). Conversion from apogeotropic to geotropic lateral canalolithiasis by the Head-Pitch Test was effective when Bow and Lean Nystagmus changed directions or when the Head-Pitch Test evoked Bow Nystagmus toward the affected side and Lean Nystagmus toward the healthy side. Conversion occurred in 10 patients during the 60 degrees forward-flexion of the head. In contrast, in 3 patients, it occurred during extension of the head, when a "Lean Nystagmus" toward the healthy side appeared. In addition, Pseudospontaneous Nystagmus and Positioning Nystagmus that arose when the patient moved from the sitting to the supine position changed direction or were evoked ex-novo, both directed toward the healthy side. In all cases, Pagnini-McClure diagnostic manoeuvre confirmed the transformation with a Positional Paroxysmal Horizontal Geotropic Nystagmus, which was more intense when the affected ear was brought down. The Head-Pitch Test can be used as the method of choice to transform apogeotropic into geotropic lateral canalolithiasis. However, anterior flexion of the head in the geotropic forms must be avoided since involuntary and harmful transformations from the geotropic into the apogeotropic form can occur, moving otoliths towards the anterior arm and cupula.

Evidence-based clinical outcome of oocyte slow cooling.

In the last few years, there has been a significant improvement in oocyte cryopreservation techniques. To investigate the clinical significance of oocyte freezing, an assessment of the cumulative pregnancy rate per started cycle derived from the use of fresh and frozen-thawed oocytes was performed. Between 2004 and 2006, 749 cycles were carried out, in which no more than three fresh oocytes were inseminated either by standard IVF or microinjection. Supernumerary mature oocytes were cryopreserved by slow cooling. Cryopreservation of fresh embryos was performed in rare cases to prevent the risk of ovarian hyperstimulation syndrome using a standard embryo freezing protocol. Fresh embryo transfer cycles totalled 680, 257 of which resulted in pregnancy. The pregnancy rates per patient and per transfer were 34.3% and 37.8% respectively. When frozen-thawed oocytes were used, following 660 thawing cycles, 590 embryo transfers were performed in 510 patients. Eighty-eight pregnancies were achieved with embryos from frozen oocytes, with a success rate of 17.2% per cycle. When fresh and frozen-thawed cycles were combined, the number of pregnancies was 355, giving a cumulative pregnancy rate of 47.4%. Oocyte cryopreservation can contribute considerably to the overall clinical success, ensuring a cumulative rate approaching that achievable with embryo storage.

Multiple mechanisms of reflex bronchospasm in guinea pigs.

The mechanisms of histamine- and bradykinin-induced reflex bronchospasm were determined in anesthetized guinea pigs. With intravenous administration, both autacoids evoked dose-dependent increases in tracheal cholinergic tone. Vagotomy or atropine prevented these tracheal reflexes. When delivered as an aerosol, bradykinin readily increased tracheal cholinergic tone, whereas histamine aerosols were much less effective at inducing tracheal reflexes. Also, unlike histamine, bradykinin could evoke profound increases in cholinergic tone without directly or indirectly (e.g., prostanoid dependent) inducing measurable airway smooth muscle contraction resulting in bronchospasm. Neither autacoid required de novo synthesis of prostanoids or nitric oxide to induce reflex tracheal contractions. Combined cyclooxygenase inhibition and tachykinin-receptor antagonism did, however, abolish all effects of bradykinin in the airways, whereas responses to histamine were unaffected by these pretreatments. The data indicate that histamine and bradykinin initiate reflex bronchospasm by differential activation of vagal afferent nerve subtypes. We speculate that selective activation of either airway C fibers or airway rapid adapting receptors can initiate reflex bronchospasm.

Characterization and regulation of tachykinin receptors in the nucleus tractus solitarius.

1. The characteristics, localization and regulation of tachykinin receptors in the rat nucleus tractus solitarius (NTS) involved in respiratory control were investigated using a combination of in vivo microinjection and in vitro autoradiographic techniques. 2. Microinjection of receptor-selective tachykinin agonists and antagonists into the NTS of urethane-anaesthetized rats suggests that stimulation of NK1 and NK3 receptors increases tidal volume, whereas NK2 and NK3 receptor activation produces a bradypnoea. 3. Depletion of NK1 receptors in the NTS due to either ageing or acute hypoxia correlates with a markedly reduced respiratory response to substance P. In contrast, chemical ablation of sensory neurons by neonatal capsaicin administration dramatically increases the respiratory response to a variety of NK1, NK2 and NK3 agonists. 4. These studies suggest that all three tachykinin receptors are present in the rat NTS and that these receptors are subject to both acute and chronic regulation.

Respiratory actions of tachykinins in the nucleus of the solitary tract: characterization of receptors using selective agonists and antagonists.

1. The respiratory response to microinjection of tachykinins and analogues into the commissural nucleus of the solitary tract (cNTS) of urethane-anaesthetized rats was investigated in the presence and absence of selective tachykinin NK(1), NK(2) and NK(3) antagonists (RP 67580, SR 48968 and SR 142801, respectively). 2. All tachykinins, except for the selective NK(2) agonist, [Nle(10)]-NKA(4-10), increased tidal volume (VT). The rank potency order of naturally-occurring tachykinins was neurokinin A (NKA)> or =substance P (SP)>>NKB, whereas the rank order for selective analogues was senktide> or = septide>> [Sar(9),Met(O(2))(11)]-SP>>[Nle(10)]-NKA(4-10). Septide (NK(1)-selective) and senktide (NK(3)-selective) were 22 fold more potent (pD(2) approximately 12) at stimulating VT than SP (pD(2) approximately 10.5). 3. Tachykinin agonists produced varying degrees of respiratory slowing, independent of changes in VT. At doses producing maximum stimulation of VT, agonists induced either a mild (<10 breaths min(-1) decrease; SP and septide), moderate (10 - 25 breaths min(-1) decrease; NKA, NKB and [Sar(9),Met(O(2)]-SP) or severe ( approximately 40 breaths min(-1) decrease; senktide) bradypnoea. [Nle(10)]-NKA(4-10) produced a dose-dependent bradypnoea without affecting VT. 4. RP 67580 significantly attenuated the VT response to SP (33 pmol) and NKA (10 pmol) but not NKB (100 pmol). In the presence of RP 67580, the mild bradypnoeic response to NKB was significantly enhanced whereas SP and NKA induced a bradyapnea which was not observed in the absence of RP 67580. SR 48968 had no effect on the VT response to SP or NKB, markedly enhanced the VT response to NKA and completely blocked the bradypnoeic response to [Nle(10)]-NKA(4-10). Only SR142801 attenuated the VT response to NKB. 5. The present data suggest that all three tachykinin receptors (NK(1), NK(2) and NK(3)) are present in the cNTS and are involved in the central control of respiration.

Respiratory actions of tachykinins in the nucleus of the solitary tract: effect of neonatal capsaicin pretreatment.

1. The respiratory response to microinjection of capsaicin and tachykinin receptor agonists into the commissural nucleus of the solitary tract (cNTS) was investigated in adult, urethane-anaesthetized rats which had been pretreated with capsaicin (50 mg kg(-1) s.c.) or vehicle (10% Tween 80, 10% ethanol in saline) as day 2 neonates. 2. Microinjection of capsaicin (1 nmol) into the cNTS of vehicle-pretreated rats, significantly reduced respiratory frequency (59 breaths min(-1), preinjection control, 106 breaths min(-1)) without affecting tidal volume (VT). In capsaicin-pretreated rats, the capsaicin-induced bradypnoea was markedly attenuated (minimum frequency, 88 breaths min(-1); control, 106 breaths min(-1)). 3. In vehicle-pretreated rats, microinjection of substance P (SP, 33 pmol), neurokinin A (NKA, 33 pmol) and NKB (330 pmol), and the selective NK(1) tachykinin receptor agonists, [Sar(9), Met(O(2))(11)]-SP (33 pmol) and septide (10 pmol), increased VT (maxima, 3.60 - 3.93 ml kg(-1)) compared with preinjection control (2.82 ml kg(-1)), without affecting frequency. The selective NK(3) agonist senktide (10 pmol) also increased VT (3.93 ml kg(-1)) which was accompanied by a bradypnoea (-25 breaths min(-1)). The selective NK(2) agonist, [Nle(10)]-NKA(4-10) (330 pmol) increased VT slightly but significantly decreased frequency (-12 breaths min(-1)). In capsaicin-pretreated rats, VT responses to SP and [Sar(9), Met(O(2))(11)]-SP were increased whereas the response to septide was abolished. Both the VT and bradypnoeic responses to senktide and [Nle(10)]-NKA(4-10) were significantly enhanced. 4. These results show that neonatal capsaicin administration markedly reduces the respiratory response to microinjection of capsaicin into the cNTS. The destruction of capsaicin-sensitive afferents appears to sensitize the NTS to SP, NKB, [Sar(9),Met(O(2))(11)]-SP, senktide and [Nle(10)]-NKA(4-10). Moreover, the loss of septide responsiveness in capsaicin-pretreated rats, suggests that 'septide-sensitive' NK(1) receptors may be located on the central terminals of afferent neurons.

Respiratory action of capsaicin microinjected into the nucleus of the solitary tract: involvement of vanilloid and tachykinin receptors.

1. The respiratory response to microinjection of capsaicin into the commissural nucleus of the solitary tract (cNTS) of urethane-anaesthetized rats was investigated in the absence and presence of the competitive vanilloid (capsaicin) antagonist, capsazepine, and selective tachykinin NK1, NK2 and NK3 antagonists (RP 67580, SR 48968 and SR 142801, respectively). 2. Microinjection of capsaicin reduced respiratory frequency but not tidal volume (VT), leading to an overall reduction in minute ventilation (VE). The effect was dose-dependent between 0.5 and 2 nmol capsaicin. Doses greater than 2 nmol produced apnoea. Tachyphylaxis was observed following repeated injection of capsaicin (1 nmol, 30 min apart). 3. Capsazepine (1 nmol) had no effect on frequency or VT when injected alone but completely blocked the respiratory response to capsaicin (1 nmol). 4. RP 67580 (1 but not 5 nmol) alone depressed frequency and VT slightly. Moreover, RP 67580 appeared to potentiate the bradypnoeic effect of capsaicin. In contrast, SR 48968 and SR 142801 (1 and 5 nmol) alone had no significant effect on respiration. However, both agents significantly attenuated the reduction in frequency produced by capsaicin. 5. In conclusion, microinjection of capsaicin into the cNTS decreases overall ventilation, primarily by reducing frequency. The action of capsaicin appears from the data to be mediated by vanilloid receptors since it is blocked by the competitive vanilloid antagonist capsazepine and is subject to tachyphylaxis. However, since NK2 (SR 48968) and NK3 (SR 142801) receptor antagonists block the actions of capsaicin, we propose that capsaicin acts also by releasing tachykinins from central afferent terminals in the cNTS.