ABSTRACT
The Prenatal Oral Health Program (pOHP) was developed to educate dental students on prenatal oral health and promote access to dental care for pregnant women. Program advancement has occurred in support of quality improvement. This mixed-methods design combined quantitative data from fourth-year dental students who participated the pOHP (N = 81) and qualitative data from a student-faculty-staff focus group discussion (N = 7). Different clinical structures, appropriate leveling in the curriculum, management with a patient care coordinator, and inclusion of interprofessional learning experiences (IPE) were compared. The survey response rate was 96.4% (N = 81). Trends were noted between students who provided clinical care for a pregnant patient (31%) versus those who did not. Results indicated that an integrated clinic was preferred, though students who had treated a pOHP patient showed greater support for a standalone clinic model. Survey and focus group data agreed that pOHP should occur during the third-year dental school training; however, students with patient experience favored second-year placement. Survey and focus group data emphasize the importance of a patient care coordinator for clinical management and IPE as an essential learning element. Innovating new clinical models requires a period of evolution to determine preferred and sustainable infrastructure. Results reveal the advantages and disadvantages of various program implementation models and demonstrate that student perceptions were influenced by their clinical experiences. Study findings will inform implementation and guide other programs as they create and modify existing curricula to enhance prenatal oral health.
ABSTRACT
BACKGROUND: Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via ß-adrenergic receptor (ßAR) activation. The contribution of distinct ßAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation. METHODS: Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal ßARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained ßAR antagonists peripherally, spinally, or supraspinally alongside OR486. RESULTS: The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective ßAR antagonist propranolol, the ß2AR antagonist ICI-118,511, or the ß3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity. CONCLUSIONS: Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting ßAR antagonists may benefit chronic pain patients.
Subject(s)
Catechol O-Methyltransferase/metabolism , Pain/enzymology , Peripheral Nervous System/drug effects , Receptors, Adrenergic, beta/drug effects , Adrenalectomy , Adrenergic beta-Antagonists/pharmacology , Animals , Behavior, Animal/drug effects , Catechol O-Methyltransferase Inhibitors/pharmacology , Catechols/pharmacology , Female , Hot Temperature , Injections, Spinal , Male , Pain Measurement/drug effects , Physical Stimulation , Propanolamines/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Catheter systems that permit targeted delivery of genes, molecules, ligands, and other agents represent an investigative tool critical to the development of clinically relevant animal models that facilitate the study of neurological health and disease. The development of new sustained catheter delivery systems to spinal and peripheral sites will reduce the need for repeated injections, while ensuring constant levels of drug in plasma and tissues. NEW METHOD: Here, we introduce two novel catheter delivery systems in the mouse: the O'Buckley intrathecal catheter system for sustained delivery to the spinal region and a subcutaneous bifurcated catheter system for sustained drug delivery to both hindpaws. RESULTS: The O'Buckley intrathecal catheter system consistently distributed Evans Blue throughout the spinal cord, with the greatest concentration at the thoracic region, and with an 85% surgery success rate. The subcutaneous catheter system consistently distributed Evans Blue to the hindlimbs, with a 100% surgery success rate. COMPARISON TO EXISTING METHOD: The O'Buckley intrathecal catheter system accomplishes sustained drug delivery to the spinal region, with a 2-fold increase in surgery success rate, as compared to the traditional method. Our subcutaneous bifurcated catheter system accomplishes sustained drug delivery to both hindpaws, eliminating the need for repeated intraplantar injections. CONCLUSIONS: We have developed catheter systems that improve upon traditional methods in order to achieve sustained localized drug delivery to spinal tissues and to hindpaw tissues surrounding peripheral sciatic nerve terminals. These methods have a broad reach, and can be used to enhance behavioral, physiologic and mechanistic studies in mice.
Subject(s)
Drug Delivery Systems/methods , Infusions, Subcutaneous/methods , Injections, Spinal/methods , Animals , Catheters , Drug Delivery Systems/instrumentation , Extremities , Female , Infusions, Subcutaneous/instrumentation , Injections, Spinal/instrumentation , Male , Mice , Mice, 129 Strain , Mice, Inbred C57BLABSTRACT
Chronic pain is a significant health care problem, ineffectively treated because of its unclear etiology and heterogeneous clinical presentation. Emerging evidence demonstrates that microRNAs (miRNAs) regulate the expression of pain-relevant genes, yet little is known about their role in chronic pain. Here, we evaluate the relationship among pain, psychological characteristics, plasma cytokines, and whole blood miRNAs in 22 healthy controls (HCs); 33 subjects with chronic pelvic pain (vestibulodynia, VBD); and 23 subjects with VBD and irritable bowel syndrome (VBD + IBS). VBD subjects were similar to HCs in self-reported pain, psychological profiles, and remote bodily pain. VBD + IBS subjects reported decreased health and function; and an increase in headaches, somatization, and remote bodily pain. Furthermore, VBD subjects exhibited a balance in proinflammatory and anti-inflammatory cytokines, whereas VBD + IBS subjects failed to exhibit a compensatory increase in anti-inflammatory cytokines. VBD subjects differed from controls in expression of 10 miRNAs of predicted importance for pain and estrogen signaling. VBD + IBS subjects differed from controls in expression of 11 miRNAs of predicted importance for pain, cell physiology, and insulin signaling. miRNA expression was correlated with pain-relevant phenotypes and cytokine levels. These results suggest that miRNAs represent a valuable tool for differentiating VBD subtypes (localized pain with apparent peripheral neurosensory disruption vs widespread pain with a central sensory contribution) that may require different treatment approaches.
Subject(s)
Chronic Pain/genetics , Gene Expression Profiling , MicroRNAs/genetics , Adult , Female , Humans , MaleABSTRACT
Decreased activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, contributes to pain in humans and animals. Previously, we demonstrated that development of COMT-dependent pain is mediated by both ß2- and ß3-adrenergic receptors (ß2ARs and ß3ARs). Here we investigated molecules downstream of ß2- and ß3ARs driving pain in animals with decreased COMT activity. Based on evidence linking their role in pain and synthesis downstream of ß2- and ß3AR stimulation, we hypothesized that nitric oxide (NO) and proinflammatory cytokines drive COMT-dependent pain. To test this, we measured plasma NO derivatives and cytokines in rats receiving the COMT inhibitor OR486 in the presence or absence of the ß2AR antagonist ICI118,551+ß3AR antagonist SR59320A. We also assessed whether the NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) and cytokine-neutralizing antibodies block the development of COMT-dependent pain. Results showed that animals receiving OR486 exhibited higher levels of NO derivatives, tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) in a ß2- and ß3AR-dependent manner. Additionally, inhibition of NO synthases and neutralization of the innate immunity cytokines TNFα, IL-1ß, and IL-6 blocked the development of COMT-dependent pain. Finally, we found that NO influences TNFα, IL-1ß, IL-6, and CCL2 levels, whereas TNFα and IL-6 influence NO levels. Altogether, these results demonstrate that ß2- and ß3ARs contribute to COMT-dependent pain, at least partly, by increasing NO and cytokines. Furthermore, they identify ß2- and ß3ARs, NO, and proinflammatory cytokines as potential therapeutic targets for pain patients with abnormalities in COMT physiology.