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The mouse ortholog of δ-tryptase, mouse mast cell protease 7 (mMCP7) has been reported to be unexpressed in C57BL/6J mice. We confirmed the absence of mMCP7 in the prostates of C57BL/6J and its presence in NOD/ShiLtJ mice. To evaluate a role for mMCP7 in the differential allodynia responses, we performed direct intra-urethral instillations of mMCP7 and the beta (β)-tryptase isoform ortholog, mMCP6 in the CP1-infection model. mMCP7, but not mMCP6 was able to induce an acute pelvic allodynia response in C57BL/6J mice. selleck products In-vitro studies with mMCP7 on cultured mast cells as well as dissociated primary neurons demonstrated the ability to induce differential activation of pain and inflammation associated molecules compared to mMCP6. We conclude that mMCP7, and possibility its human ortholog δ-tryptase, may play an important role in mediating the development of pelvic tactile allodynia in the mouse model of pelvic pain and in patients with CP/CPPS.Background Diabetic neuropathy is characterized by the paradoxical co-existence of hypo- and hyperalgesia to sensory stimuli. The literature shows consistently sensory differences between healthy and participants with diabetes. We hypothesized that due to differences in pathophysiology, advanced quantitative sensory testing (QST) might reveal sensory discrepancies between type 1 (T1D) and type 2 diabetes (T2D). Furthermore, we investigated whether vibration detection thresholds (VDT) were associated with sensory response. Method Fifty-six adults with T1D [43 years (28-58)], 99 adults with T2D [65 years (57-71)], and 122 healthy individuals [51 years (34-64)] were included. VDT, pressure pain detection thresholds (pPDT) and tolerance (pPTT), tonic cold pain (hand-immersion in iced water), and central pain mechanisms (temporal summation and conditioned pain modulation) were tested and compared between T1D and T2D. VDT was categorized into normal ( 25 V). Results In comparison to healthy, analysis adjusted for age, BMI, and gender revealed hypoalgesia to tibial (pPDT) p = 0.01, hyperalgesia to tonic cold pain p less then 0.01, and diminished temporal summation (arm p less then 0.01; abdomen p less then 0.01). In comparison to participants with T2D, participants with T1D were hypoalgesic to tibial pPDT p less then 0.01 and pPTT p less then 0.01, and lower VDT p = 0.02. VDT was not associated with QST responses. Conclusion Participants with T1D were more hypoalgesic to bone pPDT and pPTT independent of lower VDT, indicating neuronal health toward normalization. Improved understanding of differentiated sensory profiles in T1D and T2D may identify improved clinical endpoints in future trials.Patients with persistent complex limb pain represent a substantial diagnostic challenge. Physical exam, and tests such as nerve conduction, are often normal even though the patient suffers from severe pain. In 2015, we initiated a team-based approach to evaluate such patients. The approach included physicians from several specialties (Anesthesiology/Pain Medicine, Radiology, Plastic Surgery, Neurosurgery) combined with the use of advanced imaging with Magnetic Resonance Neurography (MRN). This preliminary case series discusses MRN findings identified in patients with previously difficult-to-diagnose peripheral limb pain and describes how this combination of approaches influenced our diagnosis and treatment plans. We extracted demographics, patient characteristics, presenting features, diagnostic tests performed, treatments provided, referral diagnosis and the diagnosis after interdisciplinary team evaluation from patient charts. We evaluated MRN and electrodiagnostic studies (EDX) ability to identify injured sulting from surgery. In addition, an interdisciplinary team evaluation and the use of the moderately sensitive but highly specific MRN imaging modality resulted in a change in diagnosis for a majority of patients with complex limb pain. Future studies investigating patient outcomes after diagnosis change are currently underway based on the findings of this preliminary study.Background Empathic communication and positive messages are important components of "placebo" effects and can improve patient outcomes, including pain. Communicating empathy and optimism to patients within consultations may also enhance the effects of verum, i.e., non-placebo, treatments. This is particularly relevant for osteoarthritis, which is common, costly and difficult to manage. Digital interventions can be effective tools for changing practitioner behavior. This paper describes the systematic planning, development and optimization of an online intervention-"Empathico"-to help primary healthcare practitioners enhance their communication of clinical empathy and realistic optimism during consultations. Methods The Person-Based Approach to intervention development was used. This entailed integrating insights from placebo and behavior change theory and evidence, and conducting primary and secondary qualitative research. Systematic literature reviews identified barriers, facilitators, and promising methods concerns and priorities. Conclusions We have developed an evidence-based, theoretically-grounded intervention that should enable practitioners to better harness placebo effects of communication in consultations. The extensive use of qualitative research throughout the development and optimization process ensured that Empathico is highly acceptable and meaningful to practitioners. This means that practitioners are more likely to engage with Empathico and make changes to enhance their communication of clinical empathy and realistic optimism in clinical practice. Empathico is now ready to be evaluated in a large-scale randomized trial to explore its impact on patient outcomes.Background Spinal manipulations (SMT) and mobilizations (MOB) are interventions commonly performed by many health care providers to manage musculoskeletal conditions. The clinical effects of these interventions are believed to be, at least in part, associated with their force-time characteristics. Numerous devices have been developed to measure the force-time characteristics of these modalities. The use of a device may be facilitated or limited by different factors such as its metrologic properties. Objectives This mixed-method scoping review aimed to characterize the metrologic properties of devices used to measure SMT/MOB force-time characteristics and to determine which factors may facilitate or limit the use of such devices within the context of research, education and clinical practice. Methods This study followed the Joanna Briggs Institute's framework. The literature search strategy included four concepts (1) devices, (2) measurement of SMT or MOB force-time characteristics on humans, (3) factors facilty, drift, and calibration. From the results, five themes related to the facilitating and limiting factors were developed user-friendliness and versatility, metrologic/intrinsic properties, cost and durability, technique application, and feedback. Conclusion Various devices are available to measure SMT/MOB force-time characteristics. Metrologic properties were reported for most devices, but terminology standardization is lacking. The usefulness of a device in a particular context should be determined considering the metrologic properties as well as other potential facilitating and limiting factors.Objective Exercise may reduce pain sensitivity. This phenomenon called exercise-induced hypoalgesia is observed in different types of exercises and involves the activation of endogenous pain modulation systems. Although the effect of limb exercise on pain sensitivity has often been tested, few studies explored the impact of back exercises that are often used to treat low back pain. The main objective is to measure the effect of back-muscle exercise on pain sensitivity and compare it to the effect of a limb-muscle exercise. Methods Twenty-three participants who were pain-free performed a 4-min wrist flexion isometric contraction followed by a 4-min low back extension, separated by a 20-min break. Pressure pain thresholds were tested at two low back (S1 spinous process, lumbar erector spinae muscle) and two wrist (capitate bone, wrist flexor muscles) sites before and after each exercise. For each exercise, sites were considered as remote or local in relation to the muscles contracted during the exercise. An independent sample of 11 participants was recruited to confirm the influence of low back extension on pain sensitivity. Results Wrist exercise induced a larger increase in pain sensitivity than back exercise at the remote site. Only wrist exercise induced a hypoalgesia effect at both the local and the remote sites. Back exercise induced a similar effect in the independent sample. Conclusions This study showed that back and wrist exercises induced a distinct effect on pain sensitivity in participants who were pain-free. The wrist exercise induced a systemic reduction in pain sensitivity (locally and remotely), whereas the back exercise did not. This differential effect may be present because wrist exercise induced most fatigue compared with the back exercise.

Despite the availability of evidence-based analgesic strategies, neonatal pain management continues to be suboptimal. Intranasal (IN) fentanyl is an alternative pharmacotherapy for procedural pain in neonatal units. The objective was to evaluate the effectiveness and safety of IN fentanyl for procedural pain in preterm infants.

A retrospective cohort study was conducted in infants who received IN fentanyl between May 2019 and December 2020 at an academic neonatal intensive care unit. Main outcome measures were pain responses, physiological parameters before and up to 60 min after IN fentanyl administration, and adverse events. Paired

-test and analysis of variance were used to compare pain scores and physiological parameters, respectively.

Thirteen infants received IN fentanyl on 22 occasions. Median (interquartile range [IQR]) gestational age and birthweight were 27 (25, 27.6) weeks and 850 (530, 1,030) grams, while median (IQR) post-menstrual age and weight were 30.9 (28.9, 32.9) weeks and 1,280 (945, 1,623) grams at the time of IN fentanyl administration. IN fentanyl was most used for lumbar puncture (55%) followed by insertion of epicutaneo-caval catheters (27%). There was a difference between the mean pre- and post-procedure Premature Infant Pain Profile scores of 1.3 (95% CI = 0.07, 2.5;

= 0.04). Physiological parameters did not differ before and up to 60 min post IN fentanyl administration (

> 0.05). Two adverse events (one apnea and one desaturation) were noted.

In our limited experience, IN fentanyl appears to be an alternative pharmacotherapy for procedural pain management in the absence of intravenous access in preterm infants.

In our limited experience, IN fentanyl appears to be an alternative pharmacotherapy for procedural pain management in the absence of intravenous access in preterm infants.Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of in situ gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood-brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization.

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