Biomedical subjects

Burghard F Klapp

Publications and source records attributed to Burghard F Klapp.

At least 19 recordsLinked to original sources

PubMed2007

A pilot clinical trial of the effects of coenzyme Q10 on chronic tinnitus aurium.

OBJECTIVE: To determine the short-term effects of coenzyme Q10 (CoQ10) on the antioxidative status and tinnitus expression in patients with chronic tinnitus aurium. STUDY DESIGN: A 16-week prospective nonrandomized clinical trial (n = 20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together with the plasma concentrations of CoQ10, malondialdehyde, and the total antioxidant status. RESULTS: The mean plasma CoQ10 concentration rose under external CoQ10 supply and remained elevated after medication stopped without overall effects on the tinnitus score. However, in a subgroup of 7 patients with low initial plasma CoQ10 concentration and significant increase in the plasma CoQ10 level, a clear decrease in the TQ score was observed. CONCLUSION: In patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the tinnitus expression. SIGNIFICANCE: This is the first study to examine the effect of CoQ10 in chronic tinnitus aurium.

Adult↗

PubMed2006

Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation.

Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.

Animals↗

PubMed2006

Effect of stress on eotaxin and expression of adhesion molecules in a murine model of allergic airway inflammation.

Recently we have shown that sound stress enhances allergic airway inflammation in a combined murine model. In the current study we investigated mediating factors and early kinetics of stress exacerbated allergic airway inflammation. Stress significantly increased allergen induced airway inflammation as identified by leukocyte numbers in BAL fluids. Eotaxin levels from stressed mice were significantly higher 24 h after stress. No differences were found for vascular or cellular adhesion molecule expression or cytokine levels. Our data indicate that the effect of stress on allergic airway inflammation might be mediated by the chemoattractant eotaxin, while Th2 cytokines and expression of adhesion molecules seem not to be differently regulated in stressed and non-stressed mice.

Allergens↗

PubMed2006

Peripheral injection of CCK-8S induces Fos expression in the dorsomedial hypothalamic nucleus in rats.

Peripheral cholecystokinin (CCK) plays a physiological role in the regulation of food intake. The dorsomedial hypothalamic nucleus (DMH) has been implicated in the brain regulation of food intake and satiety. The aim of this study was to determine if peripherally administered CCK affects neuronal activity in the DMH, as assessed by Fos expression. Density of Fos-positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus of the hypothalamus (ARC) and ventromedial hypothalamic nucleus (VMH) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injection of CCK-8S (2 microg/kg, n=6) or vehicle (0.15 M NaCl; n=6). CCK-8S increased Fos immunoreactivity in the DMH (mean+/-SEM; cells/section: 108+/-10 versus 54+/-6, p<0.001) and PVN (120+/-12 versus 20+/-3, p<0.001) compared to the vehicle group while not influencing Fos expression in the ARC and VMH. Double labeling showed that 27.4+/-6.4% (n=3) of Fos-positive neurons induced by CCK-8S were positive for corticotropin-releasing factor immunoreactivity, that were mainly localized in the ventral part of the DMH, and encircled in a network of tyrosine-hydroxylase-immunoreactive positive fibers. These data indicate that in addition of the PVN, peripheral CCK increases neuronal activity in the DMH suggesting a possible role in this hypothalamic nucleus in the satiating effect of the peptide.

Adrenal Cortex Hormones↗

PubMed2006

Upregulation of tumor necrosis factor-alpha by stress and substance p in a murine model of allergic airway inflammation.

OBJECTIVE: Clinical observation has suggested that stress and asthma morbidity are associated, though underlying mechanisms are not clearly understood. After having established a mouse model of stress-exacerbated allergic airway inflammation, we demonstrated a stress-mediating role for neurokinin-1 receptor, the main substance P (SP) receptor. Here, our aim was to investigate the influence of stress or exogenously applied SP on airway inflammation and on the local cytokine production of immune cells. METHODS: BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly challenged with OVA aerosol. Sound stress was applied to the animals for 24 h, starting with the first airway challenge. Alternatively, one group of non-stressed mice received intranasal SP before airway challenges. Cell numbers were determined in bronchoalveolar lavage (BAL) fluid. Leukocytes from mediastinal lymph nodes were analyzed by flow cytometry to determine the percentages of T cells producing interleukin-4, interferon-gamma and tumor necrosis factor-alpha. RESULTS: In BAL fluids of stressed or SP-treated animals, significantly higher total cell counts were found compared to non-stressed mice. In lymph nodes, the percentage of TNF-alpha-positive T cells was higher in stressed mice and mice after application of SP. In contrast, the influence of stress did not increase the percentages of interferon-gamma-positive CD3+ cells, meanwhile the application of SP increased the percentages of T cells positive for this cytokine. CONCLUSION: Our data provide further evidence for a stress-mediating neuroimmunological pathway that, putatively via SP, is able to influence the composition of immune cells in different compartments of allergic airway inflammation.

Acoustic Stimulation↗

PubMed2006

A model of peripherally developing hearing loss and tinnitus based on the role of hypoxia and ischemia.

The incidence of sensorineural hearing loss often caused by direct damage to the cochlear hair cells is by far more frequent and more serious than disorders affecting the external ear or the middle ear. Mechanisms that are discussed to be relevant for the genesis of tinnitus and acquired hearing impairment are hair cell loss, signal transduction disturbances in the region of the outer and inner hair cells and the spiral ganglion, impairment of cochlear blood flow, mechanical disturbance, and hypoxia and ischemia. The present model surveys the possible cellular and molecular biological causes of peripherally developing hearing loss and tinnitus. In particular, the paper discusses the roles of hypoxia and ischemia in the cochlea and in the etiology of the neurosensory types of tinnitus. Peripheral origins of hearing disturbances and tinnitus may be: (a) damage to the stereocilia and the tip links, (b) dysfunction of potassium channels or (c) modification of the glutamate release. Moreover, the hypoxia inducible factor-1 may have an important role to play as a key transcription factor in the cells' adaptation to hypoxia and ischemia. An impairment of the cochlear blood flow may be induced by the expression of target genes like nitrogen monoxide synthase and endothelin-1 resulting in tinnitus. The paper discusses consequences resulting from the present model for the medical treatment of peripherally developing tinnitus and hearing loss.

Cochlea↗

PubMed2006

Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage.

Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

Aging↗

PubMed2006

A modified version of tinnitus retraining therapy: observing long-term outcome and predictors.

Tinnitus retraining therapy (TRT) in Germany includes not only directive counseling and sound therapy but also stress management and facultative psychotherapeutic treatment. The aim of the present study was to investigate the impact of this modified version of TRT on certain tinnitus-related aspects of distress and variables that may predict treatment outcome. Clinical data from 92 patients undergoing outpatient TRT in the Charité Tinnitus Centre were evaluated retrospectively over 1 year. Treatment outcome was defined by changes in specific areas of tinnitus-related distress and assessed by the Tinnitus Questionnaire. Changes in audiometric frequency and loudness of tinnitus were examined by regular audiometric testing. The overall Tinnitus Questionnaire score was significantly reduced after 1 year. Severely affected tinnitus sufferers (decompensated tinnitus) profited more than less affected patients (compensated tinnitus). In cases of indicated psychotherapy, improvement was significant for the patients who took advantage of psychotherapeutic treatment during TRT but was not significant for those who interrupted or dismissed an indicated psychotherapy. Changes in tinnitus-specific areas of distress were most pronounced in the scales for emotional and cognitive distress and intrusiveness. Significant changes in sleep disturbances, auditory perceptual difficulties and somatic complaints were observed in patients with decompensated tinnitus. In patients with chronic tinnitus, modified TRT may lead to significant subjective improvement in certain tinnitus-related symptoms like emotional and cognitive distress and intrusiveness. Particularly patients suffering from severe tinnitus distress take advantage of therapy. Careful psychotherapeutic diagnostics and therapies and, if necessary, motivation to make use of psychotherapy seem to be essential preconditions for therapeutic success in patients with severe psychosomatic comorbidity.

Adult↗

PubMed2006

Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin.

The interaction between ghrelin and bombesin or amylin administered intraperitoneally on food intake and brain neuronal activity was assessed by Fos-like immunoreactivity (FLI) in nonfasted rats. Ghrelin (13 microg/kg ip) increased food intake compared with the vehicle group when measured at 30 min (g/kg: 3.66 +/- 0.80 vs. 1.68 +/- 0.42, P < 0.0087). Bombesin (8 microg/kg) injected intraperitoneally with ghrelin (13 microg/kg) blocked the orexigenic effect of ghrelin (1.18 +/- 0.41 g/kg, P < 0.0002). Bombesin alone (4 and 8 microg/kg ip) exerted a dose-related nonsignificant reduction of food intake (g/kg: 1.08 +/- 0.44, P > 0.45 and 0.55 +/- 0.34, P > 0.16, respectively). By contrast, ghrelin-induced stimulation of food intake (g/kg: 3.96 +/- 0.56 g/kg vs. vehicle 0.82 +/- 0.59, P < 0.004) was not altered by amylin (1 and 5 microg/kg ip) (g/kg: 4.37 +/- 1.12, P > 0.69, and 3.01 +/- 0.78, respectively, P > 0.37). Ghrelin increased the number of FLI-positive neurons/section in the arcuate nucleus (ARC) compared with vehicle (median: 42 vs. 19, P < 0.008). Bombesin alone (4 and 8 microg/kg ip) did not induce FLI neurons in the paraventricular nucleus of the hypothalamus (PVN) and coadministered with ghrelin did not alter ghrelin-induced FLI in the ARC. However, bombesin (8 microg/kg) with ghrelin significantly increased neuronal activity in the PVN approximately threefold compared with vehicle and approximately 1.5-fold compared with the ghrelin group. Bombesin (8 microg/kg) with ghrelin injected intraperitoneally induced Fos expression in 22.4 +/- 0.8% of CRF-immunoreactive neurons in the PVN. These results suggest that peripheral bombesin, unlike amylin, inhibits peripheral ghrelin induced food intake and enhances activation of CRF neurons in the PVN.

Amyloid↗

PubMed2006

Cerebral processing of auditory stimuli in patients with irritable bowel syndrome.

AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactivations in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affective reactivity, possibly associated with the psychological comorbidity often found in IBS patients.

Acoustic Stimulation↗

PubMed2006

Three assessment tools for deliberate self-harm and suicide behavior: evaluation and psychopathological correlates.

OBJECTIVE: The aims of this study are to adapt two validated self-report questionnaires of deliberate self-harm and suicidal behavior to German, to investigate their psychometric properties and agreement with clinician-administered ratings, and to examine their psychopathological correlates. METHODS: The Deliberate Self-Harm Inventory [Gratz KL. Measurement of deliberate self-harm: preliminary data on the deliberate self-harm inventory. J Psychopathol Behav 2001;23:253-263] and the Self-Harm Behavior Questionnaire [Guttierez PM, Osman A, Barrios FX, Kopper BA. Development and initial validation of the self-harm behavior questionnaire. J Pers Assess 2001;77:475-490] were completed by 361 patients hospitalized for depressive, anxiety, adjustment, somatoform, and/or eating disorders. A clinician-administered rating scale of self-destructive behavior was included. Psychopathological variables were assessed by standardized questionnaires. RESULTS: The self-report questionnaires demonstrated good reliability (alpha=.81-.96, split-half r=.78-.98, test-retest r=.65-.91). Reliability of the clinician-administered ratings was acceptable (interrater kappa=.46-.77, test-retest kappa=.35-.48). Intraclass correlations (ICC=.68) for all three instruments were satisfactory. Rates of self-harm and associations between self-harm and suicidal behaviors are reported. The findings support the hypotheses of a higher degree of psychiatric symptomatology in patients with self-harm behavior compared to those without. CONCLUSION: The two questionnaire adaptations are reliable and valid self-report scales for the assessment of self-harm and past suicidal behavior.

Adolescent↗

PubMed2006

[Standardized diagnosing: computer-assisted (CIDI) diagnoses compared to clinically-judged diagnoses in a psychosomatic setting].

BACKGROUND: Within the past two decades, there has been an increasing trend towards the use of empirically-based, standardized instruments to diagnose mental disorders. The purpose of this study was to investigate the congruence between clinically-derived and standardized computerized diagnoses using the Composite International Diagnostic Interview (CIDI) in a psychosomatic setting. PATIENTS AND METHODS: N = 230 inpatients treated at the Department of Psychosomatic Medicine, Charité Berlin, were diagnosed for mental disorders by experienced clinicians and by the CIDI according to the diagnostic criteria of ICD-10 and DSM-IV. RESULTS: Congruence between computerized and clinically-derived diagnoses for all mental disorders was fair to poor (kappa = 0.0 - 0.33). The diagnostic congruence of somatoform (F45), anxiety (F40 - 41), depressive (F32 - 34), eating (F50) and dissociative disorders (F44) and disorders due to psychoactive substance use (F10 - 19) was fairly low (kappa = 0.19 - 0.33). Diagnostic congruence of diagnoses of reactions to severe stress (F43) and obsessive compulsive disorders (F42) was particularly poor (kappa = 0.0 - 0.01). CONCLUSION: Overall diagnostic congruence between computerized and clinical diagnostics was unsatisfactory. Thus, the validity of computer-assisted standardized interviews - like the CIDI - is questionable in a psychosomatic setting.

Adult↗

PubMed2006

[Evaluation of the effectiveness of psychosomatic in-patient treatment on the basis of subjective and objective criteria].

OBJECTIVES: The effectiveness of psychosomatic in-patient treatment was evaluated using patients' subjective health ratings and objective data provided by health insurance companies. Associations between subjective and objective criteria were investigated. METHODS: 318 patients participated in the study. They completed questionnaires on physical complaints, moods and everyday functioning upon hospital admission, at discharge and at one-year follow-up. Insurance companies provided data for 140 of these patients (44 %). Sick leave and the utilization of in-patient treatment were assessed for a period of two years before and two years after psychosomatic treatment. RESULTS: As expected, subjective health status improved. The utilization of in-patient treatment decreased in both years after treatment compared to the year before. Sick leave increased in the first year after treatment but decreased significantly below the base level in the second year after treatment. Self-efficacy expectations and being employed were found to be predictors for long-term reduction in the length of in-patient treatment. Subjective and objective criteria were only slightly correlated. CONCLUSIONS: Sick leave and utilization of in-patient treatment were found to increase considerably in the year before psychosomatic treatment. Therefore, pre-post differences over the entire period were only marginal. The change in subjective criteria was more immediate, while changes in some objective parameters were delayed. Both subjective and objective criteria should be included in outcome studies.

Activities of Daily Living↗

PubMed2006

p75 Neurotrophin Receptor-Mediated Signaling Promotes Human Hair Follicle Regression (Catagen).

Nerve growth factor (NGF) and its apoptosis-promoting low-affinity receptor (p75NTR) regulate murine hair cycling. However, it is unknown whether human hair growth is also controlled through p75NTR, its high-affinity ligand pro-NGF, and/or the growth-promoting high-affinity NGF receptor tyrosine kinase A (TrkA). In microdissected human scalp anagen hair bulbs, mRNA for NGF, pro-NGF, p75NTR, and TrkA was transcribed. Immunohistomorphometry and in situ hybridization detected strong NGF and pro-NGF expression in terminally differentiating inner root sheath keratinocytes, whereas TrkA was co-expressed with p75NTR in basal and suprabasal outer root sheath keratinocytes. During spontaneous catagen development of organ-cultured human anagen hair follicles, p75NTR mRNA levels rose, and p75NTR and pro-NGF immunoreactivity increased dramatically in involuting compartments primarily devoid of TrkA expression. Here, TUNEL(+) apoptotic cells showed prominent p75NTR expression. Joint pro-NGF/NGF administration inhibited hair shaft elongation and accelerated catagen development in culture, which was antagonized by co-administration of p75NTR-blocking antibodies. In addition, mRNA and protein expression of transforming growth factor-beta2 increased early during spontaneous catagen development, and its neutralization blocked pro-NGF/NGF-dependent hair growth inhibition. Our findings suggest that pro-NGF/NGF interacts with transforming growth factor-beta2 and p75NTR to terminate anagen in human hair follicles, implying that p75NTR blockade may alleviate hair growth disorders characterized by excessive catagen development.

Apoptosis↗

PubMed2005

Nerve growth factor translates stress response and subsequent murine abortion via adhesion molecule-dependent pathways.

Spontaneous abortion is a frequent threat affecting 10%-25% of human pregnancies. Psychosocial stress has been suggested to be attributable for pregnancy losses by challenging the equilibrium of systems mandatory for pregnancy maintenance, including the nervous, endocrine, and immune system. Strong evidence indicates that stress-triggered abortion is mediated by adhesion molecules, i.e., intercellular adhesion molecule 1 (ICAM1) and leukocyte function associated molecule 1, now being referred to as integrin alpha L (ITGAL), which facilitate recruitment of inflammatory cells to the feto-maternal interface. The neurotrophin beta-nerve growth factor (NGFB), which has been shown to be upregulated in response to stress in multiple experimental settings including in the uterine lining (decidua) during pregnancy, increases ICAM1 expression on endothelial cells. Here, we investigated whether and how NGFB neutralization has a preventive effect on stress-triggered abortion in the murine CBA/J x DBA/2J model. We provide experimental evidence that stress exposure upregulates the frequency of abortion and the expression of uterine NGFB. Further, adhesion molecules ICAM1 and selectin platelet (SELP, formerly P-Selectin) and their ligands ITGAL and SELP ligand (SELPL, formerly P selectin glycoprotein ligand 1) respectively increase in murine deciduas in response to stress. Subsequently, decidual cytokines are biased toward a proinflammatory and abortogenic cytokine profile. Additionally, a decrease of pregnancy protective CD8alpha(+) decidual cells is present. Strikingly, all such uterine stress responses are abrogated by NGFB neutralization. Hence, NGFB acts as a proximal mediator in the hierarchical network of immune rejection by mediating an abortogenic environment comprised of classical signs of neurogenic inflammation.

Abortion, Spontaneous↗

PubMed2005

An integrative model of developing tinnitus based on recent neurobiological findings.

Brain imaging studies suggest that the functional connectivity of various limbic, prefrontal, and temporal brain structures can be understood as the basis for particularly intense experiences of impairment and many secondary symptoms of decompensated tinnitus. Results to date suggest cortical plasticity as a likely mechanism to be involved in the chronic progression of tinnitus. Relationships between the processing of auditory signals and neural networks associated with somatosensory, attentional, cognitive and emotional processes are relevant for the genesis of the pathology. However, the neural bases of subjective impairment in tinnitus patients are unknown. An integrative model of developing tinnitus is presented here, based on the most recent neurophysiological data in current discussion. We assume the involvement of altered brain functions in the development and maintenance of perceptions of tinnitus and outline various possibilities which could contribute to decompensation and chronic progression. The discussions surrounding present models of the generation of tinnitus and its reinforcement to the point of decompensation make it clear that a unidimensional approach in clinical interventions is insufficient. Patients with decompensated tinnitus suffer from a complex somatic and psychological disorder. The interactive processes involving emotions, behaviour and symptoms, as well as the high co-morbidity with affective and psychosomatic illnesses and the important influence of psychosocial factors (distress), make the use of stage-appropriate interdisciplinary treatments necessary.

Brain↗

PubMed2005

Megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood.

Hirschsprung's disease (HD) is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel. However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of HD in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient's bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify HD patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage.

Adult↗

PubMed2005

Protease-activated receptor 2 expression in trigeminal neurons innervating the rat nasal mucosa.

Protease-activated receptor 2 (PAR2) is activated by trypsin and mast cell tryptase to induce widespread inflammation by unknown mechanisms. Trypsin and tryptase were shown to activate sensory neurons to release substance-P and related peptides to mediate neurogenic inflammation. In the present study, the expression of PAR2 and tachykinins were investigated in rat trigeminal neurons that were identified by retrograde labeling with rhodamine dye from the nasal mucosa by using neuronal tracing in combination with immunohistochemistry. We found that large subpopulation of all trigeminal neurons (43.5+/-2.6%) identified by the pan-neuronal marker PGP 9.5 were stained with PAR2-immunoreactivity. Of all trigeminal neurons, 7.5+/-2.1% were immunoreactive for tachykinins and PAR2, and only 3.9+/-1.7% of all trigeminal neurons expressed tachykinins, but not PAR2-immunoreactivity. The present study also found that a large number trigeminal neurons innervating the nasal mucosa expressed PAR2-immunoreactivity. Of the rhodamine-labeled trigeminal neurons, 52.5+/-1.8% were immunoreactive for only PAR2 expression, 7.3+/-1.9% contained tachykinins and PAR2, and 3.1+/-0.4 of the rhodamine-labeled trigeminal neurons were non-immunoreactive PAR2, but were positive for tachykinins-immunoreactivity. In conclusion, based on the co-localization of PAR2 and tachykinins in trigeminal sensory neurons innervating the nasal mucosa, the present study suggests that, following an activation of PAR2 receptor in tachykinergic neurons by trypsin and mast cell tryptase, there may be a triggering of tachykinin-mediated phenomena such as neurogenic inflammation in allergic or non-allergic rhinitis.

Animals↗