Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans

BACKGROUND: Candidate gene studies on the basis of biological hypotheses have been a practical approach to identify relevant genetic variation in complex traits. Based on previous reports and the roles in pain pathways, we have examined the effects of variations of loci in the genes of monoamine neurotransmitter systems including metabolizing enzymes, receptors and transporters on acute clinical pain responses in humans. RESULTS: Variations in the catecholamine metabolizing enzyme genes (MAOA and COMT) showed significant associations with the maximum post-operative pain rating while the serotonin transporter gene (SLC6A4) showed association with the onset time of post-operative pain. Analgesic onset time after medication was significantly associated with the norepinephrine transporter gene (SLC6A2). However, the association between COMT genetic variation and pain sensitivity in our study differ from previous studies with small sample sizes, population stratification and pain phenotype derived from combining different types of pain stimuli. Correcting for multiple comparisons did not sustain these genetic associations between monoamine neurotransmitter systems and pain sensitivity even in this large and homogeneous sample. CONCLUSION: These results suggest that the previously reported associations between genetic polymorphisms in the monoamine neurotransmitter systems and the interindividual variability in pain responses cannot be replicated in a clinically relevant pain phenotype

Kinin B1 receptors contributes to acute pain following minor surgery in humans

<p>Abstract</p> <p>Background</p> <p>Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B₁and B₂receptors. It is generally accepted that the B₂receptor is constitutively expressed, whereas the B₁receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.</p> <p>Results</p> <p>Tissue injury resulted in a significant up-regulation in the gene expression of B₁and B₂receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B₁and B₂receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B₁and B₂receptors were correlated. Following tissue injury, B₁ligands des-Arg⁹-BK and des-Arg¹⁰-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B₁receptor but not B₂receptor.</p> <p>Conclusions</p> <p>These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B₁receptors may contribute to acute inflammatory pain through TRPV1 activation.</p

Unraveling the complex polymorphic crystallization behavior of the alternating copolymer DMDS-alt-DVE

[Abstract]: A complex crystallization behavior was observe the alternating copolymer DMDS-alt-step-growth polymerization. Understanding the underlying complex crystallization processes of such innovative polythioethers is critical for their application, for example, in polymer coating technologies. These alternating copolymers have polymorphic traits, resulting in different phases that may display distinct crystalline structures. The copolymer DMDS-alt-DVE was studied in an earlier work, where only two crystalline phases were reported: a low melting, L − Tm, and high melting, H − Tm phase. Remarkably, the H − Tm form was only achieved by the previous formation and melting of the L − Tm form. We applied calorimetric techniques encompassing seven orders of magnitude in scanning rates to further explore this complex polymorphic behavior. Most importantly, by rapidly quenching the sample to temperatures well below room temperature, we detected an additional polymorphic form (characterized by a very low melting phase, denoted VL − Tm). Moreover, through tailored thermal protocols, we successfully produced samples containing only one, two, or all three polymorphs, providing insights into their interrelationships. Understanding polymorphism, crystallization, and esulting morphological differences can have significant implications and potential impact on mechanical resistance and barrier roperties.Gobierno Vasco; IT1503-22Gobierno Vasco; IT-1525-22Ministerio de Ciencia e Innovación; PGC2018-094620-A-I00Xunta de Galicia; ED431F 2021/00

Targeted gene sanger sequencing should remain the first-tier genetic test for children suspected to have the five common X-linked inborn errors of immunity

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott–Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.The Hong Kong Society for Relief of Disabled Children and Jeffrey Modell Foundation.http://www.frontiersin.org/Immunologyam2023Paediatrics and Child Healt

Psicologia Social (Rr.Hh.)-AH12-201401

El curso presenta los fundamentos de la Psicología Social y sus aplicaciones a la empresa. Introduce al participante en el modo cómo la presencia de otras personas influye en nuestra conducta y cómo se originan los fenómenos de conducta social así como la influencia que se genera sobre el desarrollo del capital humano. El estudiante comprende cómo se forman los procesos grupales de liderazgo y de resistencia al cambio en las organizaciones y estudia los métodos para facilitar los procesos sociales de cooperación e integración de intereses. Este logro se demuestra a través de la redacción de un ensayo fina

Nitric oxide is negatively correlated to pain during acute inflammation

<p>Abstract</p> <p>Background</p> <p>The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied.</p> <p>Results</p> <p>Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100-180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo goup but not in the ketorolac group.</p> <p>Conclusion</p> <p>We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression.</p

Small proline-rich protein 1 is the major component of the cell envelope of normal human oral keratinocytes

AbstractOral keratinocytes of buccal and gingival tissues undergo a terminal differentiation program to form a protective epithelial barrier as non-keratinized or parakeratinized stratified cells. We have examined the protein composition of cell envelopes (CEs) from normal human buccal and gingival tissues as well as keratinocytes from normal human gingival cells grown in culture. Biochemical and sequencing analyses reveal that the CEs contain 60–70% small proline-rich protein 1a/b (SPR1a/b), together with smaller amounts of involucrin, annexin I and several other known CE proteins. The data imply a specialized role for SPR1 proteins in the unique barrier function requirements of oral epithelia