Navigating challenges and opportunities: Nursing student's views on generative AI in higher education.

AIM: This qualitative study aims to explore the perspectives of nursing students regarding the application and integration of generative Artificial Intelligence (AI) tools in their studies. BACKGROUND: With the increasing prevalence of generative AI tools in academic settings, there is a growing interest in their use among students for learning and assessments. DESIGN: Employing a qualitative descriptive design, this study used semi-structured interviews with nursing students to capture the nuanced insights of the participants. METHODS: Semi-structured interviews were digitally recorded and then transcribed verbatim. The research team reviewed all the data independently and then convened to discuss and reach a consensus on the identified themes. RESULTS: This study was conducted within the discipline of nursing at a regional Australian university. Thirteen nursing students, from both first and second year of the programme, were interviewed as part of this study. Six distinct themes emerged from the data analysis, including the educational impact of AI tools, equitable learning environment, ethical considerations of AI use, technology integration, safe and practical utility and generational differences. CONCLUSIONS: This initial exploration sheds light on the diverse perspectives of nursing students concerning the incorporation of generative AI tools in their education. It underscores the potential for both positive contributions and challenges associated with the integration of generative AI in nursing education and practice.

Differential Sensitization of Muscle versus Fascia in Individuals with Low Back Pain.

Muscles and the deep fascia surrounding them have been suggested to play an important role in various musculoskeletal pain conditions including low back pain. Both have been shown to host rich nociceptive innervation and to undergo changes in individuals with chronic pain. However, evidence for the respective contribution of muscle and fascia sensitization in humans with myofascial pain syndrome is lacking. Here, we studied the sensitization of muscle and fascia in individuals with myofascial low back pain. Twenty individuals with acute (5) and chronic (15) myofascial low back pain of the quadratus lumborum muscle and a matched control group of twenty healthy individuals were recruited and clinically evaluated. All participants underwent ultrasound-guided needling of their subcutaneous tissue, deep fascia and quadratus lumborum muscle. Reported pain intensity and episodes of muscle twitching were recorded and analyzed. Among pain patients, both muscles and deep fascia demonstrated pain hypersensitivity, but muscles were significantly more sensitized than the deep fascia. No difference between acute- or chronic-pain patients was observed. Results of this study suggest that while both deep fascia and muscle show pain sensitization in both early and chronic stages of low back pain, muscles are more sensitized than fascia.

Feasibility of Magnetic Resonance-Guided High-Intensity-Focused Ultrasound (MRgHIFU) Ablation of Stump Neuromas for the Relief of Chronic Postamputation Neuropathic Pain.

Up to 70% of limb amputees develop chronic postamputation neuropathic pain (CPANP) which includes phantom pain and residual limb neuropathic pain due to neuroma formation. CPANP often requires invasive procedures aimed at neuroma ablation. Five amputees received 6 noninvasive magnetic resonance-guided high-intensity-focused ultrasound MRgHIFU treatments ExAblate®, Insightec, Tirat-Carmel, Israel). Although ablative temperature (>65°C) at the neuroma was reached in only 1 patient, pain intensity dropped from 5.7 at baseline to 4.3 and back to 5.6 at 3 and 6 month follow-up. Post-treatment bone necrosis was demonstrated in 1 patient. Although no firm conclusion about the effectiveness of MRgHIFU for CPANP could be drawn, further studies are warranted.

Evaluation of nurses' experiences of a post education program promoting recognition and response to patient deterioration: Phase 2, clinical coach support in practice.

Front-line nurses providing around the clock care are pivotal to the identification, recognition, and response to patient deterioration. However, there is growing evidence that patient deterioration indicators are poorly managed and not escalated to rapid response teams (RRTs), contributing to adverse outcomes. Access to effective educational programs has been cited as vital in optimising nurses' recognition and response to deteriorating patients. Several studies evaluated educational programs, but have not explored nurses' experiences of engaging in patient deterioration events post attendance. Participants in a multimodal education program (DeTER) were invited to attend a series of focus groups three months post workshop as phase two of an overall study. A convenience sample of 22 acute care nurses was recruited. A qualitative descriptive design incorporating focus groups and thematic analysis was used to evaluate participants' experiences of engaging with the RRT during patient deterioration events and whether clinical coach support in practice influenced their recognition and response. Four themes were identified within the data, categorised as enhanced confidence, effective communication, supportive culture, and early response. The importance of an educational model using multimodal strategies, underpinned by coach support and guidance post workshop, was clearly demonstrated to optimise nurses' management of patient deterioration events.

Perceptions of the impact of introducing administrative support for nurse unit managers: A qualitative evaluation.

AIM: To evaluate the impacts of introducing administrative support for nurse unit managers. BACKGROUND: Increased administrative load for nurse unit managers causes role stress and reduced opportunities for clinical leadership (state-wide review, Queensland, Australia). In response, a health organisation implemented a clerical 'Nurse Unit Manager Support Officer' position. METHODS: Qualitative descriptive evaluation, convenience sample (37 nurse unit managers and NUM Support Officers) and focus groups (13) provided data that were thematically analysed. RESULTS: Six impacts were identified: (a) improved nurse unit manager well-being; (b) more time to undertake clinical leadership; (c) greater efficiencies in finance, payroll and HR processes; (d) improved capacity for strategic leadership; (e) increased staff satisfaction and improved unit culture; and (f) improved succession planning. CONCLUSION: Findings reveal significant gains and benefits from the introduction of administrative support for the nurse unit manager role for the nurse unit manager and the units they manage. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse unit manager role stress can negatively impact organisational climate, performance outcomes, staff satisfaction and retention. Health organisations need to implement strategies to reduce the administrative burden for nurse unit managers. The introduction of administrative support frees up time for nurse unit managers to engage in clinical leadership, positively impacting organisational climate, performance outcomes, and staff satisfaction and retention.

The effects of a dopamine agonist (apomorphine) on experimental and spontaneous pain in patients with chronic radicular pain: A randomized, double-blind, placebo-controlled, cross-over study.

BACKGROUND: Although evidence suggests that dopaminergic systems are involved in pain processing, the effects of dopaminergic interventions on pain remains questionable. This randomized, double blinded, placebo-controlled, cross-over study was aimed at exploring the effect of the dopamine agonist apomorphine on experimental pain evoked by cold stimulation and on spontaneous pain in patients with lumbar radicular (neuropathic) pain. METHODS: Data was collected from 35 patients with chronic lumbar radiculopathy (18 men, mean age 56.2±13 years). The following parameters were evaluated before (baseline) and 30, 75 and 120 minutes subsequent to a subcutaneous injection of 1.5 mg apomorphine or placebo: cold pain threshold and tolerance in the painful site (ice pack, affected leg) and in a remote non-painful site (12°C water bath, hand), and spontaneous (affected leg) pain intensity (NPS, 0-100). RESULTS: One-hundred and twenty minutes following apomorphine (but not placebo) injection, cold pain threshold and tolerance in the hand increased significantly compared to baseline (from a median of 8.0 seconds (IQR = 5.0) to 10 seconds (IQR = 9.0), p = 0.001 and from a median of 19.5 seconds (IQR = 30.2) to 27.0 seconds (IQR = 37.5), p<0.001, respectively). In addition, apomorphine prolonged cold pain tolerance but not threshold in the painful site (from a median of 43.0 seconds (IQR = 63.0) at baseline to 51.0 seconds (IQR = 78.0) at 120 min, p = 0.02). Apomorphine demonstrated no superiority over placebo in reducing spontaneous pain intensity. CONCLUSION: These findings are in line with previous results in healthy subjects, showing that apomorphine increases the ability to tolerate cold pain and therefore suggesting that dopaminergic interventions can have potential clinical relevance.

Methylphenidate attenuates the response to cold pain but not to aversive auditory stimuli in healthy human: a double-blind randomized controlled study.

INTRODUCTION: We recently showed that the psycho-stimulant norepinephrine-dopamine reuptake inhibitor methylphenidate (MP) prolonged cold pain threshold and tolerance in adults with attention-deficit hyperactivity disorder (ADHD). OBJECTIVES: The objectives of the present study were to: (1) examine whether MP has antinociceptive properties in healthy men; (2) test MP's effects on responses to aversive auditory stimuli. The underlying aim was to determine whether MP exerts antinociceptive properties or more generalized, nonspecific attenuating effects on different aversive sensory modalities. METHODS: This double-blind, crossover, randomized placebo-controlled study consisted of 2 sessions one week apart from each other. In each session, pain threshold (seconds) and tolerance (seconds) in response to painful cold stimulation were measured. Additionally, threshold (dB) and tolerance (seconds) to loud aversive auditory stimuli (500 Hz, 2000 Hz and white noise) were also tested prior to and 2 hours following the administration of a single dose of either 20 mg MP or an identical looking placebo. RESULTS: Forty men, 26.1 ± 4.0 (mean ± SD) years were enrolled in the study. Wilcoxon signed-rank test analyses showed that MP, but not the placebo, produced a significant increase in cold pain threshold (from 4.1 ± 2.6 to 5.4 ± 3.1 seconds, P = 0.001 and from 4.5 ± 2.6 to 4.3 ± 2.7 seconds, P = 0.2, respectively) and tolerance (from 57.8 ± 54.0 to 73.8 ± 61.8 seconds, P = 0.001 and from 52.5 ± 53.7 sec to 57.0 ± 52.9 seconds, P = 0.1, respectively). No significant changes were found in any of the auditory parameters. CONCLUSION: These results suggest that MP has an effect on nociceptive pathways rather than a nonspecific, generalized attenuating effect on aversive sensory stimuli.

Measuring the Intensity of Chronic Pain: Are the Visual Analogue Scale and the Verbal Rating Scale Interchangeable?

OBJECTIVES: The 0 to 100 mm visual analogue scale (VAS) and the five-category verbal rating scale (VRS) are commonly used for measuring pain intensity. An open question remains as to whether these scales can be used interchangeably to allow comparisons between intensities of pain in the clinical setting or increased statistical power in pain research. METHODS: Seven hundred and ninety-six patients were requested to rate the present intensity of their chronic pain on the two scales. Spearman's rank correlation coefficients between VAS and VRS were calculated. For testing interchangeability, VAS was transformed into a discrete ordinal scale by dividing the entire VAS into five categories, either equidistantly (biased) or using frequency distributions of VAS (unbiased). We used Goodman-Kruskal's gamma and Wilson's e measures of ordinal association quantified the relationships between the transformed VAS and VRS scores and Svensson method to evaluate agreement between biased and unbiased discrete VAS and VRS scales. RESULTS: Average VAS and VRS scores were 76 ± 18 mm and "severe," respectively. Spearman's rank correlation coefficient values between continuous VAS and VRS were 0.77 to 0.85. Goodman-Kruskal's gamma ordinal associations between discrete VAS and VRS were 0.82 to 0.92 and 0.90 to 0.98 for the biased and unbiased VAS, respectively. Wilson's e measures were 0.51 to 0.61 and 0.54 to 0.65, accordingly. Svensson analysis showed low probability of agreement between both biased (0.66 to 0.76) and unbiased (0.75 to 0.82) VAS and VRS. DISCUSSION: Regardless of the relatively high Spearman correlations between original VAS and VRS, the low ordinal association and low probability of agreement between discrete VAS and VRS suggest that they are not interchangeable. Therefore, VAS and VRS should not be used interchangeably in the clinical setting or for increased statistical power in pain research.

The effect of hydromorphone therapy on psychophysical measurements of the descending inhibitory pain systems in patients with chronic radicular pain.

OBJECTIVE: Conditioned pain modulation (CPM) and offset analgesia (OA) are considered to represent paradigms of descending inhibitory pain modulation in humans. This study tested the effects of hydromorphone therapy on descending inhibitory pain modulation, as measured by changes from baseline in the magnitudes of CPM and OA. DESIGN: Prospective evaluation. SETTING: Institute of Pain Medicine, Rambam Health Care Campus. SUBJECTS: Patients with chronic radicular pain. METHODS: Thirty patients received 4 weeks of oral hydromorphone treatment at an individually titrated dose (mean ± standard deviation dose of 11.6 ± 4.8 mg/day). CPM and OA were assessed before and after hydromorphone treatment. CPM was assessed by subtracting the response to a painful phasic heat stimulus administered simultaneously with a conditioning cold pain stimulus, from the response to the same heat stimulus administered alone. The OA paradigm consisted of a three-temperature stimuli train (T1 = 49°C [5 seconds], T2 = 50°C [5 seconds], and T3 = 49°C [20 seconds]). The magnitude of OA was quantified by subtracting minimal pain scores obtained during T3 from the maximal pain scores obtained during T2. RESULTS: CPM scores changed from a baseline of 17.7 ± 20.6 to 21 ± 20.4 following treatment, and OA scores changed from 7.8 ± 20.5 to 9.7 ± 14.6. Wilcoxon signed rank test indicated that these changes were not significant (CPM: P = 0.22; OA: P = 0.44). McNemar test revealed that the percentage of patients who exhibited a change in the direction of CPM or OA in response to hydromorphone treatment was not significant (CPM: P = 0.37; OA: P = 0.48). CONCLUSIONS: These results suggest that the descending inhibitory pain modulation, as manifested in humans by CPM and OA, is unlikely to be mediated by hydromorphone therapy.

Surface electromyographic recordings after passive and active motion along the posterior myofascial kinematic chain in healthy male subjects.

OBJECTIVE: To map the association of muscle activations along the superficial back line (SBL) using separate conditions of active range of motion with and without resistance and passive range of motion. METHOD: Using surface electromyography, electrodes were placed at specific points along the SBL. Twenty healthy adult males (aged 25.35 ± 1.24 years and body mass index 23.78 ± 2.12) underwent five test conditions. Conditions 1-3 involved passive movement, active movement and active movement against maximum isometric resistance (IR) of the right gastrocnemius and conditions 4 and 5 involved neck extension without and with isometric resistance from prone position. RESULTS: Passive and active motion without resistance found no significant (p > 0.05) correlations at any electrodes. Maximum IR yielded significant (p < 0.05) correlations with medium to very strong correlations at almost all electrodes. Neck extension without and with resistance showed significant medium to very strong correlations though the posterior superior iliac spine and right hamstring, respectively. CONCLUSION: Results demonstrated significant associations between the test condition muscle activations and muscle activations along the contiguous SBL. Thus, showing a need for a complete evaluation of the SBL in patients suffering from myofascial pain at all locations along it.

Oxycodone alters temporal summation but not conditioned pain modulation: preclinical findings and possible relations to mechanisms of opioid analgesia.

Opioid analgesia is mediated primarily by modulating (inhibiting and enhancing) pain mechanisms at the spinal and supraspinal levels. Advanced psychophysical paradigms of temporal summation (TS) and conditioned pain modulation (CPM) likely represent pain mechanisms at both levels. Therefore, the study of opioid effects on TS and CPM can shed light on their analgesic mechanisms in humans. The current randomized, double-blind study tested the effects of oxycodone on the magnitude of both TS and CPM in 40 healthy subjects. TS was tested by measuring increments in pain intensity in response to 10 repetitive painful phasic heat stimuli. CPM was assessed by subtracting the response to a painful phasic heat stimulus administrated simultaneously with a conditioning cold pain stimulus from a painful phasic heat stimulus alone. These paradigms were tested before and at 60, 120, and 180 minutes after administration of a single oral dose of either oxycodone or an active placebo. Repeated-measures analysis of variance revealed significant effects of oxycodone, but not placebo, on the magnitude of TS (F=7.196, P<.001). Pairwise comparisons revealed that relative to baseline, TS was significantly reduced at 60 minutes (P=.008) and at 180 minutes (P=.017) after oxycodone administration. In contrast, no significant effects of either oxycodone (F=0.871, P=.458) or placebo (F=2.086, P=.106) on the magnitude of CPM were found. These results suggest that under the current experimental conditions, oxycodone exerted spinal, rather than supraspinal, analgesic effects. Furthermore, compared with CPM, TS seems more suitable for studying the mechanisms of opioid analgesia in humans.

Anti tumor necrosis factor - alpha adalimumab for complex regional pain syndrome type 1 (CRPS-I): a case series.

BACKGROUND AND AIMS: Evidence suggests tumor necrosis factor-alpha (TNF-α) mediates, at least in part, symptoms and signs in complex regional pain syndrome (CRPS). Here, we present a case series of patients with CRPS type 1, in whom the response to the anti-TNF-α adalimumab was assessed. METHODS: Ten patients with CRPS type 1 were recruited. Assessments were performed before treatment, at 1 week, and 1, 3, and 6 months following 3 biweekly subcutaneous injections (40 mg/0.8 mL) adalimumab (Humira(®) ) and included the followings: Pain intensity using a 0-10 cm visual analog scale; the Short Form of the McGill Pain Questionnaire; the Beck Depression Inventory; the SF-36 questionnaire and mechanical and thermal thresholds (Von frey hair and Thermal Sensory Analyzer, respectively). In addition to the description of individual patient responses, both intention to treat (ITT) and per-protocol (PP) analyses were performed for the entire group. RESULTS: Three subgroups of patients were identified (3 patients in each): "nonresponders", "partial responders", and "robust responders" in whom improvement in almost all parameters was noted. Both the ITT and PP analyses demonstrated only a trend toward improvement in mechanical pain thresholds following treatment (ITT χ² = 13.83, P = 0.008; PP χ² = 10.29, P = 0.036). CONCLUSION: These results suggest adalimumab, and possibly other anti-TNF-α, can be potentially useful in some (although not in all) patients with CRPS type 1. These preliminary results along with the growing body of evidence which points to the involvement of TNF-α in the pathogenesis of CRPS justify further studies in this area.

A negative correlation between hyperalgesia and analgesia in patients with chronic radicular pain: is hydromorphone therapy a double-edged sword?

BACKGROUND: Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Yet, unconfirmed evidence suggests that chronic exposure to opioids may cause hypersensitivity to pain, a phenomenon known as opioid-induced hyperalgesia (OIH). OBJECTIVES: The current preliminary prospective study was aimed to explore the relationship between experimental OIH and clinical opioid induced analgesia (OIA) in a model of experimental OIH in patients with chronic radicular pain using intermediate-term opioid therapy. STUDY DESIGN: Prospective evaluation SETTING: Interdisciplinary Pain Clinic at a referral Health Care Campus METHODS: Thirty patients with chronic neuropathic (radicular) pain were assessed prior to and following 4 weeks of an individually titrated dose of oral hydromorphone treatment (4-20 mg/d). The assessments included an evaluation of experimental OIH by testing for heat pain intensity and cold pain tolerance and an assessment of OIA by completing pain and disability questionnaires. RESULTS: Hydromorphone was found to induce hyperalgesia, as measured by an elevation of phasic heat pain intensity (P < 0.05). At the same time, hydromorphone caused significant clinical analgesic effects. There was a notable reduction in average daily pain scores (primary analgesic outcome) of 26 Visual Analog Scale (0-100) points. A significant negative correlation was found between OIH and all OIA measures (r = -0.389, P < 0.05 for the primary analgesic outcome). Hydromorphone dosage was positively correlated with OIH (P < 0.01, r = 0.467) and negatively correlated with OIA parameters (r = -0.592, P < 0.01 for the primary analgesia outcome). LIMITATIONS: The nonrandomized, open-label, prospective evaluation. CONCLUSION: A 4-week regimen of open-label hydromorphone therapy results in a dose-dependent OIH, which negatively correlates with its analgesic effect. Future randomized, controlled, and blinded studies are needed to verify these preliminary results. 

Association between polymorphisms in serotonin and dopamine-related genes and endogenous pain modulation.

UNLABELLED: Genetic studies have become indispensable in understanding pain mechanisms, shedding light on the role of monoamine pathways in pain modulation. The present study was aimed to explore the relationship between functional polymorphisms in serotonin and dopamine-related genes and pain modulation. Two paradigms of pain modulation were administered to 191 healthy participants in a random order: Conditioned Pain Modulation in response to painful stimuli (CPM(painful)) tested by the coadministration of repeated short painful heat stimuli and a conditioning tonic cold pain stimulation; and Conditioned Pain Modulation in response to nonpainful stimuli (CPM(nonpainful)) tested similarly, except for using a painless conditioning stimulation. Using the Transmission Disequilibrium Test (TDT), functional variable number of tandem repeat (VNTR) polymorphisms of the following candidate genes were studied: 1) serotonin transporter (5-HTTLPR); 2) dopamine transporter (DAT1); 3) dopamine receptor 4 (DRD4); and 4) monoamine oxidase A (MAOA). DNA samples from both participants and their parents were analyzed. A significant association was found between CPM(nonpainful) and the 5-HTTLPR polymorphism (P = .001). More specifically, carriers of the long allele exhibited a significantly higher magnitude of CPM(nonpainful) than carriers of the short allele. No associations were found between the dopamine-related genes and both types of pain modulation. These results highlight the importance of serotonin in endogenous analgesia. PERSPECTIVE: This article presents an association between the serotonin transporter gene polymorphism (5-HTTLPR) and pain modulation derived by nonpainful conditioned pain modulation (CPM(nonpainful)), rather than painful conditioned pain modulation (CPM(painful)). These findings emphasize the complex role of serotonin in pain modulation, and highlight the importance of genetic studies in the understanding of interindividual differences in sensitivity to pain.

Predicting the analgesic effect to oxycodone by 'static' and 'dynamic' quantitative sensory testing in healthy subjects.

The large inter-individual variability in the magnitude of analgesia in response to opioids and the high prevalence of adverse events associated with their use underline the clinical importance of being able to predict who will or will not respond to opioid treatment. The present study used both static and dynamic quantitative sensory testing (QST) on 40 healthy volunteers in order to test whether this methodology can predict the analgesic effects of oral oxycodone, as compared to a placebo, on latency to onset, pain intensity, and tolerance to the cold pressor test (CPT). Static QST consisted of measuring heat and cold pain thresholds. Dynamic QST included measurements of the magnitude of the diffuse noxious inhibitory control (DNIC)-like effect and of temporal summation (TS). Results showed that oxycodone, but not the placebo, significantly elevated the latency and tolerance to cold pain and significantly reduced pain intensity. The static QST results showed that heat pain thresholds predicted the magnitude of reduction in pain intensity in response to oxycodone treatment (F((1,22))=5.63, p=0.027, R(2)=0.17). The dynamic QST results showed that TS predicted the effect of oxycodone on the tolerance to CPT (F((1,38))=9.11, p=0.005, R(2)=0.17). These results suggest that both static and dynamic QST have the potential to be useful in the prediction of the response to opioid treatment.

Factors affecting - and relationships between-different modes of endogenous pain modulation in healthy volunteers.

UNLABELLED: Endogenous analgesia (EA) can be reflected by diffuse noxious inhibitory control (DNIC), non-noxious inhibitory control (NNIC) and habituation to repeated painful stimuli. However, the coexistence of these phenomena in a given individual and the degree to which various factors predict their magnitudes have not been fully investigated. Using experimental paradigms of DNIC, NNIC and habituation, the present study explored the relationships between - and the contribution factors to - the magnitude of EA exhibited by healthy volunteers (n=191; 104 F, 87 M) exposed to these three experimental paradigms. Each subject was assigned to all three paradigms (DNIC-tested by co-administering repeated short painful heat stimuli and a conditioning tonic cold pain stimulation; NNIC - tested similarly with the exception of using a painless conditioning stimulation; habituation - tested by applying repeated painful heat stimuli only) in a random order. Pain intensities decreased from baseline in all three paradigms. However, DNIC produced significantly more pain reduction than the other two modes (RM-ANOVA). The magnitude of pain reduction of DNIC was found to be highly correlated with that of NNIC and habituation (r=0.56, p<0.001 for both correlations). A hierarchical regression analysis showed that baseline (p<0.001) and conditioning pain scores (p=0.043) predicted the magnitude of DNIC. A gender split analysis showed that conditioning pain scores served as a predictive factor for men only. CONCLUSIONS: Under these experimental conditions, different EA conditions seem to be related to each other. High initial pain intensities predict 'effective' DNIC and habituation, whereas intensity of the conditioning stimulus determines the magnitude of DNIC in men only.

Associations between polymorphisms in dopamine neurotransmitter pathway genes and pain response in healthy humans.

Although evidence shows that several dopamine neurotransmission pathway genes are associated with specific clinical pain syndromes, such as fibromyalgia, chronic headache, and postoperative pain, the exact role of dopamine in pain processing is not fully understood. The aim of this study was to explore the relationship between functional polymorphisms in dopaminergic candidate genes and sensitivity to pain in healthy subjects. Healthy subjects (n=192; 105 F, 87 M) were exposed to experimental tonic cold pain (1 degrees C) and phasic heat pain (47 degrees C) stimuli. DNA samples were obtained from both participants and their parents. The relationships between pain response (intensity in response to heat and cold; threshold and tolerance in response to cold only) and the functional Variable Number of Tandem Repeat (VNTR) polymorphisms of three dopamine-related genes were investigated using a Transmission Disequilibrium Test (TDT). Specifically, 30-bp repeat in the promoter region of the monoamine oxidase-A gene (MAO-A), 40-bp repeat in the 3'-untranslated region of the dopamine transporter gene (DAT-1), and 48-bp repeat in the exon 3 of the dopamine receptor 4 gene (DRD4) were examined. Significant associations between cold pain tolerance and DAT-1 (p=0.008) and MAO-A (p=0.024) polymorphisms were found. Specifically, tolerance was shorter for carriers of allele 10 and the rarer allele 11, as compared to homozygous for allele 9, and for carriers of allele 4 as compared to homozygous for allele 3, respectively. These results, together with the known function of the investigated candidate gene polymorphisms, suggest that low dopaminergic activity can be associated with high pain sensitivity and vice versa.

Oral opioid use alters DNIC but not cold pain perception in patients with chronic pain - new perspective of opioid-induced hyperalgesia.

Opioids can elicit unexpected changes in pain sensitivity, known as opioid-induced hyperalgesia (OIH). The aim of this study was to explore whether OIH exists in patients with chronic pain treated with oral opioids (OP) versus non-opioid (NOP) analgesics. The sensitivity to cold pain and the magnitude of diffuse noxious inhibitory control (DNIC) were evaluated in 73 OP and 37 NOP treated patients. Pain threshold, intensity and tolerance in response to the cold pressor (1 degrees C) were measured. DNIC was tested by co-administrating conditioned heat stimulation (47 degrees C) to the left forearm and a conditioning stimulation of 12 degrees C for 30s to the right hand. The results showed no differences between the two groups in any of the cold pain measures. In contrast, the magnitude of DNIC was significantly larger in the NOP than in the OP treated patients (p=0.003). A gender based analysis showed a significant difference in DNIC between OP and NOP treated men only. However, a mixed model ANOVA demonstrated a significant effect of treatment (OP versus NOP) (F=5.928, p=0.017) rather than gender on DNIC. A regression analysis showed that opioid dosage and treatment duration had a significant negative effect on the magnitude of DNIC in OP treated men (beta=-2.175, p=0.036 and beta=-2.061, p=0.047, respectively). In conclusion, oral opioids usage for the treatment of chronic pain does not result in abnormal sensitivity to cold pain, but seems to alter pain modulation. The use of 'advanced' psychophysics tests such as evaluation of DNIC can help understanding the phenomenon of OIH.

Further delineation of the odonto-onycho-dermal dysplasia syndrome.

We report on three boys, two brothers and their maternal cousin, presenting with dry hair, pilar keratosis, severe hypodontia, smooth tongue, onychodysplasia, and keratoderma and hyperhidrosis of palms and soles. Histology of the skin showed orthokeratotic, hyperkeratosis, hypergranulosis, and mild acanthosis in the epidermis. Scanning electron microscopic examination of the hair showed longitudinal depressions in some hair. These features are close to a rare entity: the odonto-onycho-dermal dysplasia but with some differing features.

Human chromosome 7: DNA sequence and biology.

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.