Sex-related differences in pain

This article provides an overview of sex-related differences in musculoskeletal pain and the role sex hormones and response to analgesic drugs may play in these differences. Some common pain conditions that include temporomandibular disorders, rheumatoid arthritis, fibromyalgia syndrome and tension-type and migraine headaches, show fairly marked sex-related differences in their occurrence, however, with the exception of rheumatoid arthritis, these pain conditions are also characterized by a lack of understanding of their basic underlying pathophysiology. The association of pain symptoms of these musculoskeletal pain conditions with the reproductive cycle of women is strongly suggestive of a role of the estrogens and/or progesterones, the main female sex hormones, in sex-related differences in pain. Nevertheless, an alternative suggestion that testosterone, the major male sex hormone, protects men from these chronic musculoskeletal pain conditions, has also been made. Indeed, emerging evidence suggests that both male and female sex hormones may contribute to the marked sex-related differences in the occurrence of certain musculoskeletal pain conditions. Men and women also appear to differ in response to pain treatment with certain analgesic drugs. The mechanistic basis for these sex-related differences is not entirely understood but sex hormones are thought to be one of the influencing factors. An improved understanding of mechanisms which underlie sex-related differences in musculoskeletal pain and response to analgesic drugs should permit improved pain management strategies for male and female musculoskeletal pain patients in the clinical setting.     

Patellofemoral pain syndrome in Iranian female athletes

Patellofemoral pain syndrome (PFPS) is the most common overuse syndrome in athletes. It is one of the causes of anterior knee pain in athletic population who come to the sports medicine clinic. Patellofemoral pain is more common among female athletes especially adolescents and young adults. Symptoms include: persistent pain behind the patella or peripatella. Pain increases on ascending and descending stairs and squatting and prolonged sitting. The aim of this study was to evaluate the prevalence of PFPS in Iranian female athletes. 418 female athletes aged 15-35 years were examined in five sports: Soccer (190), volleyball (103), running (42), fencing (45) and rock climbing (38). The athletes who had non- traumatic onset anterior knee pain of at least 3 months that increased in descending and ascending stairs and squatting, had no other causes of anterior knee pain such as ligament instability, bursitis, meniscal injury, tendonitis and arthritis and no history of knee surgery during the one past year were diagnosed as PFPS. 26/190 (13.68 %) soccer players, 21/103(20.38 %) volleyball players, 7/42 (16.66 %) runners, 6/45(13.33 %) fencers and 10/38 (26.31%) rock climbers had patellofemoral pain. Among the 418 female athletes who were evaluated 70 had PFPS. Rock climbers were the most common athletes with PFPS followed by volleyball players and runners.     

Activation of p38 mitogen-activated protein kinase is critical step for acquisition of effector function in cytokine-activated T cells, but acts as a negative regulator in T cells activated through the T-cell receptor

Peripheral blood CD4⁺ CD45RO⁺ T cells activated in vitro are able to induce expression of tumour necrosis factor‐α (TNF‐α) in monocytes via a contact‐dependent mechanism. Activation is achieved either with interleukin‐2 (IL‐2)/IL‐6/TNF‐α over an 8‐day period or cross‐linking CD3 using anti‐CD3 antibody for 48 hr. In this paper, we show that the p38 mitogen‐activated protein kinase (MAPK) signalling pathway played different roles in the generation of effector function in these two types of activated T cells. In anti‐CD3 activated T cells, p38 MAPK is a negative regulator for anti‐CD3 induced cell proliferation and has no significant effect on the acquisition of either the effector function (induction of monocyte‐derived TNF‐α) or production of T‐cell cytokines. In contrast, the p38 MAPK signalling pathway is required for the acquisition of cytokine‐induced effector function and promotes cell proliferation and cytokine production.     

Enhancing drugs absorption through third-degree burn wound eschar

Antimicrobial therapy remains the most important method of wound infection treatment. Systemically administered antimicrobials may not achieve therapeutic levels in wound. On the other hand, some topically applied antimicrobials cannot penetrate eschar well enough. Therefore, an attempt has been made here to increase permeation of topically applied drugs through eschar using the so-called skin penetration enhancers. To perform this investigation, effects of different potential penetration enhancers on permeation of chlorhexidine, silver sulfadiazine and nitroglycerin through human third-degree burn eschar was evaluated. Results showed that water, glycerin, saline, sodium lauryl sulphate (SDS) and ethanol tend to reduce permeation of chlorhexidine through burn eschar. But, water, glycerin, hexane:ethanol and ethyl acetate:ethanol were able to increase permeation of silver sulfadiazine significantly by about 1.2-1.8 times, while saline, SDS and dimethyl sulfoxide were not able to change its permeation. Glycine showed 2.7 times enhancement toward permeation of nitroglycerin, followed by water, hexane:ethanol mixture, saline and SDS with enhancement ratios of 1.8-2.3. Urea, ethanol and citral were not able to increase permeation of nitroglycerin through eschar. This study shows that permeation of drugs through burn eschar can be improved by penetration enhancement including hydration; the effect depends on the nature of the penetrant.     

Eliciting preferences for continuing medication among adult patients and parents of children with attention‐deficit hyperactivity disorder

BackgroundAdherence to medication for attention‐deficit hyperactivity disorder (ADHD) is less than optimal. Previous studies have primarily focused on qualitative assessment of factors that influence medication adherence.ObjectiveThis study aimed to quantify the factors that influence patient and parent preferences for continuing ADHD medication.MethodA discrete‐choice experiment was conducted to investigate preferences. Adults, and parents of children, with ADHD were presented with eight hypothetical choice tasks of three options (Medication A, Medication B, No Medication) described by six attributes related to medication outcomes. Preferences were estimated using a mixed multinomial logit model.ResultsOverall, respondents'' preferences (n = 216) for continuing medication were negative (mean [β] = −1.426, p < .001); however, a significant heterogeneity in preferences was observed amongst respondents (standard deviation = 0.805, p < .001). Improvements in education, aggressive behaviour, social behaviour and family functioning, and side effects and stigma, influenced respondents'' decision to continue taking medication. The respondents were willing to continue medication if they experienced positive effects, but side effects (even moderate) were the strongest concern for not continuing medication. While side effects were the most important factor for both adult patients and parents of children with ADHD, improvement in education was relatively more important for adults and improvement in aggressive behaviour, social behaviour and family functioning was relatively more important for parents of children with ADHD. Parents were more likely to not continue a medication with severe side effects even at the highest level of improvement in education.ConclusionsSide effects are the most important factor that influenced preferences for continuing medication for both adults with ADHD, as well as parents of children with ADHD. While overall the respondents preferred not to take/give medication, discrete‐choice experiment showed that the relative importance of factors that influenced continuation of medications was different for the two groups.Patient and Public InvolvementAdults, and parents of children, with ADHD participated in this study by completing the online questionnaire. The questionnaire was based on findings of research in the literature, as well as earlier focus groups conducted with adults, and parents of children, with ADHD. The face validity of the questionnaire was determined by asking parents of children, and adults, with ADHD (n = 3) to complete the survey and participate in a short discussion on their understanding of the questions and their recommendations on improving the clarity of the survey.     

Immunobiology and privilege of neuronal retina and pigment epithelium transplants

Despite the existence of ocular immune privilege, immune rejection may be a barrier to successful retinal transplantation. We have examined in mice the extent to which the subretinal space (SRS) is an immune privileged site, and whether retinal pigment epithelium and neuronal retinal tissue have properties of immune privileged tissues. We report that (1) The SRS is an immune privileged site; (2) Neonatal RPE is an immune privileged tissue; (3) Neuronal retina is a partially immune privileged tissue; and (4) Microglia within neonatal neural retina grafts promote photoreceptor differentiation, become activated, and induce sensitization of the recipient and serve as targets of immune rejection.     

Identifying and treating resistant hypertension in PRECISION: A randomized long‐term clinical trial with aprocitentan

The design and baseline data of the PRECISION study, which evaluates the effect of the dual endothelin receptor antagonist aprocitentan on blood pressure (BP) in patients with resistant hypertension (RHT) are presented. The study is a blinded, randomized, parallel‐group Phase 3 study and its three‐part design assesses the short‐term and sustained long‐term effects of aprocitentan on BP. Results are expected in 2022.Patients with uncontrolled BP (measured as unattended automated office BP) despite the use of three or more antihypertensive medications for at least 1 year were screened. They were switched to a single‐tablet triple fixed combination antihypertensive therapy for at least 4 weeks before entering a single‐blind placebo run‐in period. The 4‐week placebo run‐in period further excluded placebo responders. The randomization period consisted of three sequential parts: (1) a 4‐week double‐blind part with aprocitentan 12.5 mg, 25 mg, or placebo (1:1:1 ratio); (2) a 32‐week single‐blind part with aprocitentan 25 mg; and (3) a 12‐week randomized withdrawal part with aprocitentan 25 mg or placebo (1:1 ratio). The purpose was to demonstrate the BP lowering effect of aprocitentan in RHT (Part 1) and the persistence of this effect (Parts 2 and 3).Out of 1965 screened patients, 730 were randomized resulting in an overall inclusion failure rate of 62.8%. The most common reason for exclusion (44.4% of all screened patients) was failure to meet the BP inclusion criteria. These results underline the high proportion of pseudoresistant hypertension among patients referred for RHT.     

Gold nanoparticle decorated dithiocarbamate modified natural boehmite as a catalyst for the synthesis of biologically essential propargylamines

Here, we prepare an Au NP decorated dithiocarbamate functionalized boehmite (γ-AlO(OH)@C-NHCS₂H·Au_NPs). This stepwise synthetic method gives an efficient, cost-effective, and green heterogenous Au-based nanocatalyst for the A³-coupling preparation of the biologically essential propargylamines. Different characterization methods, including FT-IR, XRD, SEM, TEM, EDX spectra, and elemental SEM-mapping, were employed to investigate the structure of the manufactured γ-AlO(OH)@C-NHCS₂H·Au_NPs. Then we used the prepared composite as a heterogeneous gold-based nanocatalyst for the one-pot A³-coupling preparation of propargyl amines by reacting a variety of aldehydes, amines, and phenylacetylene which exhibited promising results.

Here, we prepare an Au NP decorated dithiocarbamate functionalized boehmite (γ-AlO(OH)@C-NHCS₂H·Au_NPs).