Stakeholder perceptions of gerodontology education for final year Australian dental school curricula.

AIM: The study explored the perceptions of final-year Australian dental students, directors of nursing, and consumer representatives toward geriatric education provided at Australian undergraduate dental schools. Findings will strengthen and inform future curricula design for dental schools. METHODS: Semi-structured interviews and focus groups were conducted through videoconferencing and in-person interviews, and analyzed using thematic analysis. RESULTS: Thematic analysis found the major themes to include relationships, curriculum variation, resources, and in-service learning experiences. The participants found gaps in the current delivery of undergraduate dental education. Solutions included greater resourcing through funding and time allocated to supervisors and a curriculum dedicated to gerodontology. CONCLUSIONS: Healthcare professional curriculum design must consider the needs of the learners and stakeholders involved in the health of older people. The focus group participants found multiple barriers and gaps to achieving what is required to adequately prepare dental graduates for an older, frail, and care-dependent population. For curricula to be successful, policymakers and education providers must find solutions to ensure that the oral health needs of older Australians are addressed and managed appropriately.

Australian dental school academics' perceptions of gerodontology education in the undergraduate curriculum.

INTRODUCTION: Australia's rapidly growing population of dentate, frail, care-dependent older people require graduates skilled in managing the health needs of this patient group. The perceptions of academics teaching gerodontology may inform future dental curricula recommendations. This study explored the perceptions of gerodontology education amongst Australian dental school academics. MATERIALS AND METHODS: All nine Australian dental schools providing entry-to-practice dentistry programs were invited to participate in semi-structured interviews. Academics from six dentistry programs took part, and the data were analysed using a thematic approach. RESULTS: The three main themes identified from interviews included 'clinical exposure', 'organisational levers', and 'sociological barriers'. The attitudes of students, as well as society and health professionals, were seen as strongly influential in preparing the workforce for managing the oral health of older people. The themes inter-linked with a knock-on effect where societal attitudes and organisational levers impact on the ability to successfully support students' preparation for gerodontology practice. Limited resources were barriers to achieving ideal learning and teaching and continued upon graduation as oral health care for older people was perceived as undervalued and under-resourced. CONCLUSION: There has been a continued cycle of failure in healthcare schemes and advocacy for the improvement of oral health for older people which has contributed to the inadequate preparation of dental graduates for managing frail and care-dependent older people. Organisational, societal, and political change is needed to support the education of dental students in this area to ensure graduate dentists are competent to manage the oral care needs of this growing population.

Articaine: dental practitioner use, basis of perception and evidence-based dentistry-a cross-sectional study.

BACKGROUND: Limited data exist on dental practitioner use and perceptions of articaine. This study is a cross-sectional survey of dental practitioners from January, 2021 to ascertain the extent of their use of the dental local anaesthetic, articaine, the basis of their perceptions about articaine and whether current practices are in line with recent evidence regarding articaine safety and efficacy. METHOD: An anonymous survey was designed using the SAP Qualtrics Core XM software platform and a survey link was disseminated from December 2020 to January 2021 via social media. The survey was designed as a five minute, anonymous, online questionnaire including a plain language information sheet, request for participant consent and 14 questions. Data were entered onto a Microsoft™ Excel spreadsheet and analysed qualitatively, isolating the answers into recurrent themes. RESULTS: Sixty percent of the surveyed dental practitioner used articaine as their preferred dental anaesthetic. Twenty-three percent of the dental practitioner surveyed used articaine for all of their dental procedures including inferior alveolar nerve blocks, while 40% of respondents used articaine for all their dental procedures except inferior alveolar nerve blocks. The predominant basis of dental practitioner uses and perception of articaine were their countries dental guidelines. CONCLUSION: Despite the latest findings that articaine is as safe and more efficacious as lidocaine for all routine dental treatment, 40% of survey respondents avoided articaine use for inferior alveolar blocks. Our study recognises a discrepancy between reported clinical practice and current research evidence. Further research and clarifications are needed to achieve ubiquitous practice of evidence-based dentistry.

A systematic review investigating patient knowledge and awareness on the association between oral health and their systemic condition.

BACKGROUND: The prevalence of the oral-systemic relationship has accounted for potentially preventable chronic conditions and morbidity worldwide. Health literacy is a large contributing factor. This systematic review investigates the knowledge and awareness of patients with major systemic conditions, regarding the oral associations to their condition. METHODS: Electronic databases including Medline (Ovid), CINAHL, The Cochrane Library, Web of Science, Informit Health Databases and Scopus were searched. All articles from 2011 to 2020, investigating knowledge of the oral-systemic link, of adult patients with the following major system conditions were searched: diabetes mellitus (DM), respiratory disease, cardiovascular disease (CVD), pregnancy and bone disease. Two independent reviewers completed screening, data extraction and quality assessment. A synthesis without meta-analysis was conducted. Twenty-four studies, from 14 different countries, were included in the systematic review. RESULTS: Analysis showed that globally, patients with major systemic conditions have poor knowledge and awareness (< 50%) of the oral health associations to their condition. Improvements in health education are particularly necessary for patients with heart disease, bone disease and diabetes. Dentists and the media were the most common source of information. There were no relevant studies investigating the knowledge of patients with respiratory disease. CONCLUSION: To improve the global burden of preventable chronic conditions, it is essential to address inequalities in the dissemination of health education to at-risk populations. Improvements in patient education rely on an increase in patient-practitioner communication on the oral-systemic link, implementation of oral health educational programs and greater interdisciplinary collaboration.

Articaine in dentistry: an overview of the evidence and meta-analysis of the latest randomised controlled trials on articaine safety and efficacy compared to lidocaine for routine dental treatment.

OBJECTIVES: To comprehensively review the existing studies of articaine in dentistry and conduct a systematic review and meta-analysis to answer the following Population, Intervention, Comparison and Outcome question: "Is articaine a safe and efficacious local anaesthetic for routine dental treatment compared to lidocaine?" METHODS: Database searches were conducted in Medline Ovid, Medline Pubmed, Scopus, Emcare, Proquest and the Cochrane Central register of Controlled Trials. Inclusion criteria were all existing English, human, randomised controlled trials of interventions involving 4% articaine and 2% lidocaine in routine dental treatment. Twelve studies were included for meta-analysis using Cochrane Review Manager 5 software. Anaesthetic success odds ratios were calculated using a random-effects model. RESULTS: Articaine had a higher likelihood of achieving anaesthetic success than lidocaine overall and in all subgroup analyses with varying degrees of significance. Overall (OR: 2.17, 95% CI: 1.50, 3.15, I2 = 62%) articaine had 2.17 times the likelihood of anaesthetic success of lidocaine (P < 0.0001). For mandibular blocks (OR: 1.50, 95% CI: 1.14, 1.98, I2 = 0%) articaine had 1.5 times the likelihood of anaesthetic success of lidocaine (P = 0.004). For all infiltrations, maxillary and mandibular (OR: 2.78, 95% CI: 1.61, 4.79, I2 = 66%) articaine had 2.78 times the likelihood of anaesthetic success of lidocaine (P = 0.0002). None of the studies reported any major local anaesthetic-related adverse effects as a result of the interventions. CONCLUSIONS: Articaine is a safe and efficacious local anaesthetic for all routine dental procedures in patients of all ages, and more likely to achieve successful anaesthesia than lidocaine in routine dental treatment. Neither anaesthetic has a higher association with anaesthetic-related adverse effects.

Adjusting to university: Perceptions of first-year health professions students.

BACKGROUND: The transition experience into university can be challenging for health profession students as they are required to rapidly learn diverse and adaptable problem solving skills and advanced reflective thinking processes which are necessary to address complex patient-care problems, particularly in the face of uncertainty within a dynamic and rapidly evolving learning environment. METHODS: A mixed-methods study was conducted to identify factors influencing this transition for first-year medical, dental, and pharmacy students at a regional Australian university. The Student Adaption to College Questionnaire (SACQ) examined participants' levels of adjustment to university, while Schlossberg's 4 S transition model was utilised in a framework analysis of the focus group and interview responses. RESULTS: Complete survey responses were obtained from 198 students, 17 of whom also participated in focus group discussions or interviews. Mean adjustment ratings obtained from the SACQ responses were academic (6.09 ± 1.3) personal-emotional (5.53 ± 1.55), social (6.30 ± 1.38), and institutional attachment (6.96 ± 1.6). These results indicate that the personal and emotional aspects of this transition were more challenging for the students. Analysis of the qualitative data revealed that generally, for these highly motivated health-professions students, dropping out of university was not an option and this had a positive influence on their ability to adjust to their new learning environment. Nonetheless, the transition involved role change; school-leavers were excited about their newly found independence, while for mature-aged students, returning to university allowed them to pursue their lifelong dreams. Adjustment was more challenging for international, mature-aged and female students, with personal and social factors influencing the transition for each of these demographic groups. CONCLUSIONS: To facilitate smooth transition into university, tertiary education institutions must consider tailored on-going support strategies that promote social interaction among students with varied backgrounds and personal characteristics.

Cone beam computed tomography in dentistry: practitioner awareness and attitudes. A scoping review.

Familiarity with cone beam computed tomography is a requisite for all dental practitioners involved in its use or referral. This scoping review examines the knowledge, attitudes, competence and confidence of dental practitioners and students towards cone beam computed tomography in the dental setting. A search of Medline, Scopus, Web of Science and Cumulative Index to Nursing and Allied Health Literature was conducted to identify and chart existing evidence. Relevant studies written in English and published after 1998 and up to July 2020 were included. Of 679 papers, 39 studies were included for analysis. Key findings include deficient knowledge despite a widespread recognition of its importance and willingness to increase proficiency in its use, as well as a largely positive and optimistic view of the technology. Future studies on practitioners' knowledge and attitudes towards cone beam computed tomography are suggested to consider the contexts of an Australian setting.

Professionally Delivered Local Antimicrobials in the Treatment of Patients with Periodontitis-A Narrative Review.

This review sheds light on the recent published scientific evidence relating to the use of professionally delivered local antimicrobial agents (LA's). The review also analyses drug delivery systems available to date and provides an update on the latest scientific evidence about the benefits, limitations, and clinical results obtained by use of local drugs in the treatment of periodontal disease. The search strategy revealed randomized controlled trials (RCTs) that compared the efficacy of adjunctive LA's to mechanical therapy alone. Based on the available evidence gathered from this review, we can infer that the use of local antimicrobial agents in conjunction to scaling and root debridement (SRD) delivers significant benefits in periodontal therapy and it is a useful aid, avoiding many of the side effects that systemic antibiotic therapy may involve. Local drug delivery (LDD) is an efficient and effective means of delivering drugs based on the evidence presented in the review. The authors of this review would suggest the use of local antimicrobials in cases of localized periodontitis or individual areas that do not respond to the usual mechanical therapy alone. This review summarizes the current use of local drug delivery in periodontal management ensuring that the general practitioners are able to choose an appropriate local antimicrobial.

The pathology of Chironex fleckeri venom and known biological mechanisms.

The large box jellyfish Chironex fleckeri is found in northern Australian waters. A sting from this cubozoan species can kill within minutes. From clinical and animal studies, symptoms comprise severe pain, welts, scarring, hypotension, vasospasms, cardiac irregularities and cardiac arrest. At present, there is no cure and opioids are used to manage pain. Antivenom is available but controversy exists over its effectiveness. Experimental and combination therapies performed in vitro and in vivo have shown varied efficacy. These inconsistent results are likely a consequence of the different methods used to extract venom. Recent omics analysis has shed light on the systems of C. fleckeri venom action, including new toxin classes that use pore formation, cell membrane collapse and ion channel modulation. This review covers what is known on C. fleckeri pathomechanisms and highlights current gaps in knowledge. A more complete understanding of the mechanisms of C. fleckeri venom-induced pathology may lead to novel treatments and possibly, the discovery of novel cell pathways, novel drug scaffolds and novel drug targets for human disease.

Australian Scorpion Hormurus waigiensis Venom Fractions Show Broad Bioactivity Through Modulation of Bio-Impedance and Cytosolic Calcium.

Scorpion venoms are a rich source of bioactive molecules, but characterisation of toxin peptides affecting cytosolic Ca2+, central to cell signalling and cell death, is limited. We undertook a functional screening of the venom of the Australian scorpion Hormurus waigiensis to determine the breadth of Ca2+ mobilisation. A human embryonic kidney (HEK293) cell line stably expressing the genetically encoded Ca2+ reporter GCaMP5G and the rabbit type 1 ryanodine receptor (RyR1) was developed as a biosensor. Size-exclusion Fast Protein Liquid Chromatography separated the venom into 53 fractions, constituting 12 chromatographic peaks. Liquid chromatography mass spectroscopy identified 182 distinct molecules with 3 to 63 components per peak. The molecular weights varied from 258 Da-13.6 kDa, with 53% under 1 kDa. The majority of the venom chromatographic peaks (tested as six venom pools) were found to reversibly modulate cell monolayer bioimpedance, detected using the xCELLigence platform (ACEA Biosciences). Confocal Ca2+ imaging showed 9/14 peak samples, with molecules spanning the molecular size range, increased cytosolic Ca2+ mobilization. H. waigiensis venom Ca2+ activity was correlated with changes in bio-impedance, reflecting multi-modal toxin actions on cell physiology across the venom proteome.

Scorpion toxin peptide action at the ion channel subunit level.

This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'

Prospective signs of cleidocranial dysplasia in Cebpb deficiency.

BACKGROUND: Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (Cebpb) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in Cebpb deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of Cebpb, using a sample of Cebpb-/-, Cebpb+/- and Cebpb+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (µCT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with µCT. Masseter and temporal muscles were collected and weighed. Expression of Cebpb was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique. RESULTS: Cebpb-/- mice displayed hypoplastic clavicles, a narrow thoracic cage, and a downward tilted zygomatic arch (p < 0.001). Although Cebpb+/- mice did not show the phenotypes above (p = 0.357), a larger mass percentage of temporal muscles over masseter muscles was seen in Cebpb+/- littermates (p = 0.012). The mRNA expression of Cebpb was detected in the clavicle, the zygoma, the temporal muscle and the masseter muscle, respectively. CONCLUSIONS: Prospective signs of CCD were identified in mice with Cebpb deficiency. These could provide an additional aetiological factor of CCD. Succeeding investigation into interactions among Cebpb, Runx2 and musculoskeletal development is indicated.

N-glycosylation determines ionic permeability and desensitization of the TRPV1 capsaicin receptor.

The balance of glycosylation and deglycosylation of ion channels can markedly influence their function and regulation. However, the functional importance of glycosylation of the TRPV1 receptor, a key sensor of pain-sensing nerves, is not well understood, and whether TRPV1 is glycosylated in neurons is unclear. We report that TRPV1 is N-glycosylated and that N-glycosylation is a major determinant of capsaicin-evoked desensitization and ionic permeability. Both N-glycosylated and unglycosylated TRPV1 was detected in extracts of peripheral sensory nerves by Western blotting. TRPV1 expressed in HEK-293 cells exhibited various degrees of glycosylation. A mutant of asparagine 604 (N604T) was not glycosylated but did not alter plasma membrane expression of TRPV1. Capsaicin-evoked increases in intracellular calcium ([Ca(2+)](i)) were sustained in wild-type TRPV1 HEK-293 cells but were rapidly desensitized in N604T TRPV1 cells. There was marked cell-to-cell variability in capsaicin responses and desensitization between individual cells expressing wild-type TRPV1 but highly uniform responses in cells expressing N604T TRPV1, consistent with variable levels of glycosylation of the wild-type channel. These differences were also apparent when wild-type or N604T TRPV1-GFP fusion proteins were expressed in neurons from trpv1(-/-) mice. Capsaicin evoked a marked, concentration-dependent increase in uptake of the large cationic dye YO-PRO-1 in cells expressing wild-type TRPV1, indicative of loss of ion selectivity, that was completely absent in cells expressing N604T TRPV1. Thus, TRPV1 is variably N-glycosylated and glycosylation is a key determinant of capsaicin regulation of TRPV1 desensitization and permeability. Our findings suggest that physiological or pathological alterations in TRPV1 glycosylation would affect TRPV1 function and pain transmission.

Neurochemical classification and projection targets of CART peptide immunoreactive neurons in sensory and parasympathetic ganglia of the head.

The aims of the present study were to determine if there is neuronal Cocaine and amphetamine regulated transcripts (CART) peptide expression (CART+) in parasympathetic (sphenopalatine (SPG); otic (OG)) and sensory (trigeminal (TG)) ganglia of the head and to examine the neurochemical phenotype (calcitonin gene-related peptide (CGRP), neurofilament 200 (NF200), isolectin B4 (IB4) binding, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and enkephalin (ENK) immunoreactivity) and projection targets (lacrimal gland (LG), parotid gland (PG), nasal mucosa (NM), temporomandibular joint (TMJ), middle cerebral artery (MCA) and middle meningeal artery (MMA)) of CART expressing neurons in these ganglia. We found CART+ neurons in both the SPG (5.25±0.07%) and OG (4.32±0.66). A significant proportion of these CART+ neurons contained VIP, NPY or ENK (34%, 26% and 11%, respectively). SPG neurons retrogradely labelled from the lacrimal gland (29%) were CART+, but we were unable to demonstrate CART+ labelling in any of the SPG or OG neurons labelled from other targets. This supports a role for CART peptides in lacrimation or regulation of vascular tone in the lacrimal gland, but not in salivation or nasal congestion. CART+ neurons were also present in the trigeminal ganglion (1.26±0.38%), where their size distribution was confined almost completely to neurons smaller than 800 µm2 (mean=410 µm2; 98%<800 µm2), and were almost always CGRP+, but did not bind IB4. This is consistent with a role for CART peptides in trigeminal pain. However, there were few CART+ neurons amongst any of the trigeminal neurons retrogradely labelled from the targets we investigated and thus we cannot comment on the tissue type where such pain may have originated. Our study shows that some specialization of CART peptide expression (based on neurochemical phenotype and target projection) is evident in sensory and parasympathetic ganglia of the head.

Early emergence of neural activity in the developing mouse enteric nervous system.

Neurons of the enteric nervous system (ENS) arise from neural crest cells that migrate into and along the developing gastrointestinal tract. A subpopulation of these neural-crest derived cells express pan-neuronal markers early in development, shortly after they first enter the gut. However, it is unknown whether these early enteric "neurons" are electrically active. In this study we used live Ca(2+) imaging to examine the activity of enteric neurons from mice at embryonic day 11.5 (E11.5), E12.5, E15.5, and E18.5 that were dissociated and cultured overnight. PGP9.5-immunoreactive neurons from E11.5 gut cultures responded to electrical field stimulation with fast [Ca(2+)](i) transients that were sensitive to TTX and ω-conotoxin GVIA, suggesting roles for voltage-gated Na(+) channels and N-type voltage-gated Ca(2+) channels. E11.5 neurons were also responsive to the nicotinic cholinergic agonist, dimethylphenylpiperazinium, and to ATP. In addition, spontaneous [Ca(2+)](i) transients were present. Similar responses were observed in neurons from older embryonic gut. Whole-cell patch-clamp recordings performed on E12.5 enteric neurons after 2-10 h in culture revealed that these neurons fired both spontaneous and evoked action potentials. Together, our results show that enteric neurons exhibit mature forms of activity at early stages of ENS development. This is the first investigation to directly examine the presence of neural activity during enteric neuron development. Along with the spinal cord and hindbrain, the ENS appears to be one of the earliest parts of the nervous system to exhibit electrical activity.

Postnatal maturation of the hyperpolarization-activated cation current, I(h), in trigeminal sensory neurons.

Hyperpolarization-activated inward currents (I(h)) contribute to neuronal excitability in sensory neurons. Four subtypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate I(h), with different activation kinetics and cAMP sensitivities. The aim of the present study was to examine the postnatal development of I(h) and HCN channel subunits in trigeminal ganglion (TG) neurons. I(h) was investigated in acutely dissociated TG neurons from rats aged between postnatal day (P)1 and P35 with whole cell patch-clamp electrophysiology. In voltage-clamp studies, I(h) was activated by a series of hyperpolarizing voltage steps from -40 mV to -120 mV in -10-mV increments. Tail currents from a common voltage step (-100 mV) were used to determine I(h) voltage dependence. I(h) activation was faster in older rats and occurred at more depolarized potentials; the half-maximal activation voltage (V(1/2)) changed from -89.4 mV (P1) to -81.6 mV (P35). In current-clamp studies, blocking I(h) with ZD7288 caused membrane hyperpolarization and increases in action potential half-duration at all postnatal ages examined. ZD7288 also reduced the action potential firing frequency in multiple-firing neurons. Western blot analysis of the TG detected immunoreactive bands corresponding to all HCN subtypes. HCN1 and HCN2 band density increased with postnatal age, whereas the low-intensity HCN3 and moderate-intensity HCN4 bands were not changed. This study suggests that functional I(h) are activated in rat trigeminal sensory neurons from P1 during postnatal development, have an increasing role with age, and modify neuronal excitability.

Peripheral targets of 5-HT(1D) receptor immunoreactive trigeminal ganglion neurons.

OBJECTIVE: The aim of the current study was to determine the proportion of trigeminal primary afferent neurons that innervate the intracranial vasculature, and other craniofacial tissues, that are also 5 hydroxy triptamine (5-HT)(1D) receptor immunoreactive. METHODS: Retrograde tracing and immunohistochemistry was used to identify 5-HT(1D) receptor labeled trigeminal primary afferent neurons that innervate the lacrimal gland (n = 3 animals), nasal mucosa (n = 3 animals), and the intracranial vasculature (middle meningeal artery in the dura [n = 3 animals] and middle cerebral artery [n = 3 animals]). RESULTS: The percentage of neurons that were 5-HT(1D) receptor immunoreactive was greater for primary afferent neurons innervating the middle meningeal artery (41.8 ± 1%) than those innervating the middle cerebral artery (28.4 ± 0.8%), nasal mucosa (25.6 ± 1%), or lacrimal gland (23.5 ± 3%). For each retrograde labeled population, the 5-HT(1D) receptor immunoreactive cells were among the smallest of the retrograde labeled cells. CONCLUSIONS: These findings provide a basis for understanding the role of 5-HT(1D) receptor agonists (eg, triptans) in the treatment of primary vascular headaches and suggest that the selectivity of triptans in the treatment of these headaches does not appear to result from specific localization of the 5-HT(1D) receptor to trigeminovascular neurons alone.

5-HT(1D) receptor immunoreactivity in the sphenopalatine ganglion: implications for the efficacy of triptans in the treatment of autonomic signs associated with cluster headache.

OBJECTIVE: To determine if 5-HT(1D) receptors are located in the sphenopalatine ganglion. BACKGROUND: While the 5-HT(1D) receptor has been described in sensory and sympathetic ganglia in the head, it was not known whether they were also located in parasympathetic ganglia. METHODS: We used retrograde labeling combined with immunohistochemistry to examine 5-HT(1D) receptor immunoreactivity in rat sphenopalatine ganglion neurons that project to the lacrimal gland, nasal mucosa, cerebral vasculature, and trigeminal ganglion. RESULTS: We found 5-HT(1D) receptor immunoreactivity in nerve terminals around postganglionic cell bodies within the sphenopalatine ganglion. All 5-HT(1D) -immunoreactive terminals were also immunoreactive for calcitonin gene-related peptide but not vesicular acetylcholine transporter, suggesting that they were sensory and not preganglionic parasympathetic fibers. Our retrograde labeling studies showed that approximately 30% of sphenopalatine ganglion neurons innervating the lacrimal gland, 23% innervating the nasal mucosa, and 39% innervating the trigeminal ganglion were in apparent contact with 5-HT(1D) receptor containing nerve terminals. CONCLUSION: These data suggest that 5-HT(1D) receptors within primary afferent neurons that innervate the sphenopalatine ganglion are in a position to modulate the excitability of postganglionic parasympathetic neurons that innervate the lacrimal gland and nasal mucosa, as well as the trigeminal ganglion. This has implications for triptan (5-HT(1D) receptor agonist) actions on parasympathetic symptoms in cluster headache.

Hyperpolarization-activated cyclic-nucleotide gated 4 (HCN4) protein is expressed in a subset of rat dorsal root and trigeminal ganglion neurons.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels are active at resting membrane potential and thus are likely to contribute to neuronal excitability. Four HCN channel subunits (HCN1-4) have previously been cloned. The aim of the current study was to investigate the immunoreactivity of HCN4 channel protein in rat trigeminal (TG) and dorsal root ganglion (DRG) sensory neurons. HCN4 was present in 9% of TG neurons and 4.7% of DRG neurons, it was distributed in a discrete population of small-diameter neurons in the TG but was located in cells of all sizes in the DRG. Approximately two thirds of HCN4-containing neurons in each ganglia were labelled with antisera raised against the 200-kDa neurofilament (NF200). The remaining HCN4-containing neurons were NF200-negative, were not labelled with antisera raised against calcitonin-gene related peptide (CGRP), and did not bind the isolectin B4 (IB4). HCN4-containing neurons made up more than half of the population of small-diameter primary afferent neurons that did not contain either NF200 or CGRP or bind IB4 in both TG and DRG. This population was not insignificant, comprising 5% of TG neurons and 2% of DRG neurons.