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Degradable polymeric vehicles for postoperative pain management.

Effective control of pain management has the potential to significantly decrease the need for prescription opioids following a surgical procedure. While extended release products for pain management are available commercially, the implementation of a device that safely and reliably provides extended analgesia and is sufficiently flexible to facilitate a diverse array of release profiles would serve to advance patient comfort, quality of care and compliance following surgical procedures. Herein, we review current polymeric systems that could be utilized in new, controlled post-operative pain management devices and highlight where opportunities for improvement exist.

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Prevalence of back and neck pain in Germany. Results from the BURDEN 2020 Burden of Disease Study.

Back and neck pain are widespread and can significantly reduce quality of life. A cross-sectional telephone survey (N=5,009) was carried out between October 2019 and March 2020 to gain a valid estimate of the prevalence of back and neck pain among adults in Germany. In addition to the frequency and intensity of back and neck pain, the study collected information about quality of life and comorbidity. The findings showed that 61.3% of respondents reported back pain in the last twelve months. Lower back pain was reported about twice as often as upper back pain, with 15.5% of respondents stating that they experienced chronic back pain. 45.7% reported neck pain, and 15.6% of respondents have experienced lower and upper back pain in addition to neck pain in the past year. Women are affected by all types of pain more often than men. About half of the respondents categorise their back or neck pain as moderate; older respondents report significantly more pain episodes per month than younger respondents. The results described here provide a comprehensive picture of the population-related limitations associated with back and neck pain and are used within the framework of the BURDEN 2020 study to quantify key indicators of burden of disease calculation.

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Evaluating rimegepant for the treatment of migraine.

Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that plays an essential role in the pathophysiology of migraine, a highly disabling neurovascular disorder characterized by severe headache attacks. Rimegepant is a small-molecule CGRP receptor antagonist that is approved by the FDA for the acute treatment of migraine and currently under investigation for migraine prophylaxis.

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Observation of others’ painful heat stimulation involves responses in the spinal cord.

Observing others' aversive experiences is central to know what is dangerous for ourselves. Hence, observation often elicits behavioral and physiological responses comparable to first-hand aversive experiences and engages overlapping brain activation. While brain activation to first-hand aversive experiences relies on connections to the spinal cord, it is unresolved whether merely observing aversive stimulation also involves responses in the spinal cord. Here, we show that observation of others receiving painful heat stimulation involves neural responses in the spinal cord, located in the same cervical segment as first-hand heat pain. However, while first-hand painful experiences are coded within dorsolateral regions of the spinal cord, observation of others' painful heat stimulation involves medial regions. Dorsolateral areas that process first-hand pain exhibit negative responses when observing pain in others. Our results suggest a distinct processing between self and others' pain in the spinal cord when integrating social information.

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Considering sex as a biological variable will require a global shift in science culture.

For over half a century, male rodents have been the default model organism in preclinical neuroscience research, a convention that has likely contributed to higher rates of misdiagnosis and adverse side effects from drug treatment in women. Studying both sexes could help to rectify these public health problems, but incentive structures in publishing and career advancement deter many researchers from doing so. Moreover, funding agency directives to include male and female animals and human participants in grant proposals lack mechanisms to hold recipients accountable. In this Perspective, we highlight areas of behavioral, cellular and systems neuroscience in which fundamental sex differences have been identified, demonstrating that truly rigorous science must include males and females. We call for a cultural and structural change in how we conduct research and evaluate scientific progress, realigning our professional reward systems and experimental standards to produce a more equitable, representative and therefore translational body of knowledge.

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Odontoblast TRPC5 channels signal cold pain in teeth.

Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5's relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system.

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Dimethyl Fumarate Reduces Oxidative Stress and Pronociceptive Immune Responses in a Murine Model of Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a highly disabling cause of pain often precipitated by surgery or trauma to a limb. Both innate and adaptive immunological changes contribute to this syndrome. Dimethyl fumarate (DMF) works through the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor and other targets to activate antioxidant systems and to suppress immune system activation. We hypothesized that DMF would reduce nociceptive, functional, and immunological changes measured in a model of CRPS.

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Outcome Goals and Health Care Preferences of Older Adults With Multiple Chronic Conditions.

Older adults with multiple chronic conditions (MCCs) vary in their health outcome goals and the health care that they prefer to receive to achieve these goals.

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The partial saphenous nerve injury model of pain impairs reward-related learning but not reward sensitivity or motivation.

Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.

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Reporting heterogeneity of treatment effects.

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