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Beyond the high: Mapping patterns of use and motives for use of cannabis as medicine.

In Denmark the boundaries between cannabis as an illicit drug and licit medicine have shifted rapidly in recent years, affecting also policy. However, the vast majority of Danes, who use cannabis as medicine (CaM) continue to rely on the unregulated market for supply. This study explores patterns of use and motives for use of CaM in Denmark.

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Social deprivation and paediatric chronic pain referrals in Ireland: a cross-sectional study.

Social deprivation is associated with a higher prevalence of chronic pain in children and an under-representation in specialist paediatric chronic pain programs. Our primary objective was to determine if there was a relationship between social deprivation and paediatric chronic pain referrals in Ireland. Secondary objectives included analysing for differences between deprivation groups in pain characteristics and function that are recorded at first clinic visit.

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Capsaicin 8% patch Qutenza and other current treatments for neuropathic pain in chemotherapy-induced peripheral neuropathy (CIPN).

Current oral treatments for neuropathic pain associated with chemotherapy-induced peripheral neuropathy (CIPN) have limited clinical efficacy, and undesirable side-effects. Topically delivered treatments have the advantage of avoiding CNS side-effects, while relieving pain. We have reviewed treatments of neuropathic pain associated with CIPN, focusing on the Capsaicin 8% patch, which can provide pain relief for up to 3 months or longer after a single 30-60-min application.

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Therapeutic effect of modulating the NLRP3-regulated transforming growth factor-β signaling pathway on interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder with complex pathogenesis and lacks effective treatment. Chronic inflammation is the main pathogenesis of Hunner-type IC/BPS. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome-related transforming growth factor-β (TGF-β)/Smad signaling pathway plays a crucial role in inflammation-related tissue fibrosis. Lipopolysaccharide (LPS) and protamine sulfate (LPS/PS) were instilled into the mouse bladder twice a week for 5 consecutive weeks to establish a chronic inflammation-induced IC/BPS model (LPS/PS model). Following LPS/PS treatment, curcumin (oral, 100 mg/kg; a potent NLRP3 modulator) was administered for 2 weeks in the curcumin treatment group, and normal saline was used for the sham group. Bladder function was evaluated by performing the voiding spot assay and examining the status of urothelial denudation and fibrosis in bladder tissues. The expression of NLRP3 inflammasome, interleukin-1β, TGF-β, Smad, vimentin, and E-cadherin in bladder tissues was evaluated through immunohistochemistry staining. Results revealed that the repeated instillation of LPS/PS leads to voiding dysfunction, bladder urothelium denudation, and detrusor muscle fibrosis through the upregulation of the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway and the increased epithelial-mesenchymal transition process in bladder tissues. The downregulation of the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway in bladder tissues through curcumin effectively mitigated bladder injury in the LPS/PS model. In conclusion, the NLRP3 inflammasome/IL-1β-related TGF-β/Smad pathway plays a crucial role in bladder injury in the LPS/PS model, and modulation of this pathway, such as by using curcumin, can effectively mitigate the sequelae of chronic inflammation-induced IC/BPS.

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Spinal A3 adenosine receptor activation acutely restores morphine antinociception in opioid tolerant male rats.

Opioids are potent analgesics, but their pain-relieving effects diminish with repeated use. The reduction in analgesic potency is a hallmark of opioid analgesic tolerance, which hampers opioid pain therapy. In the central nervous system, opioid analgesia is critically modulated by adenosine, a purine nucleoside implicated in the beneficial and detrimental actions of opioid medications. Here, we focus on the A adenosine receptor (A AR) in opioid analgesic tolerance. Intrathecal administration of the A AR agonist MRS5698 with daily systemic morphine in male rats attenuated the reduction in morphine antinociception over 7 days. In rats with established morphine tolerance, intrathecal MRS5698 partially restored the antinociceptive effects of morphine. However, when MRS5698 was discontinued, these animals displayed a reduced antinociceptive response to morphine. Our results suggest that MRS5698 acutely and transiently potentiates morphine antinociception in tolerant rats. By contrast, in morphine-naïve rats MRS5698 treatment did not impact thermal nociceptive threshold or affect antinociceptive response to a single injection of morphine. Furthermore, we found that morphine-induced adenosine release in cerebrospinal fluid was blunted in tolerant animals, but total spinal A AR expression was not affected. Collectively, our findings indicate that spinal A AR activation acutely potentiates morphine antinociception in the opioid tolerant state.

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Update on pain in arthritis.

Osteoarthritis is a degenerative joint disease that features pain as a hallmark symptom. This review summarises progress and obstacles in our understanding of pain mechanisms in arthritis.

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Not just preaching to the CHOIR-A map for improving comprehensive care of patients with chronic migraine and comorbid non-cephalic pain.

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Pain by mistake: investigating a link between error-related negativity and pain avoidance behavior.

Pain can be considered as a signal of "bodily error": Errors put organisms at danger and activate behavioral defensive systems. If the error is of physical nature, pain is the warning signal that motivates protective action such as avoidance behavior to safeguard our body's integrity. Interestingly, an important component of neural error processing, the error-related negativity (ERN), has been found to be related to avoidance in anxiety disorders. The present study is the first to extend these findings to pain and investigate the relationship between ERN and pain-related avoidance behavior. It was hypothesized that individuals with larger ERN amplitudes would show more pain-related avoidance behavior and would be more persistent in their avoidance despite changes in the environment. Fifty-three healthy individuals performed the Eriksen Flanker task during which their brain activity upon correct and erroneous motor responses was recorded by means of high-density electroencephalography. Avoidance behavior was assessed with an arm-reaching task using the HapticMaster robot arm. Results showed that, in contrast to our hypothesis, avoidance was not related to ERN amplitudes. Surprisingly, persons with elevated ERN amplitudes showed low levels of avoidance specifically during early acquisition trials. In contrast to earlier findings in anxiety disorders, individuals with elevated ERN amplitudes did not engage in more pain-related avoidance behavior. In fact, the opposite pattern was found at the start of acquisition: individuals with higher compared to lower ERN amplitudes were slower in learning to avoid pain. Replications and future studies on the relationship between ERN and avoidance behavior are needed.

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The effect of social support in chronic back pain: number of treatment sessions and reported level of disability.

Chronic back pain is characterized by its duration and poor response to medical interventions and is a major health problem. Treatment up-take, adherence, and social support are key issues and are vital for recovery and functionality. However, there is limited research on the role of social support and treatment uptake and adherence for chronic back pain. The aim of this study was to explore the impact of social support in terms of treatment uptake and adherence in chronic back pain patients in Australia. Two hundred and one adult men and women completed a battery of questionnaires that assessed levels of social support and disability and treatment uptake and adherence. Stepwise multiple regression predicting treatment participation, produced a significant model that included participant's age and level of social support and accounted for 14% of the variance, (2,179) = 14.10,  < 0.001, adj  = 0.14. Life control, affective distress and level of social support scores accounted for 26% of the variance in disability levels (3,179) = 21.42,  < 0.001, adj  = 0.26. The findings indicated that age, social support had a significant positive effect on the number of treatment sessions attended by participants and that life control, affective distress, and level of social support were negatively related to disability levels. The findings support interdisciplinary approaches, including social interventions as important part of any chronic back pain treatment. Implications for rehabilitation Chronic back pain does not respond well to traditional rehabilitation methods based on the Medical Model. Social support has a significant impact on treatment adherence and disability. This study measures perceived social support from an emotional and instrumental perspective. Social support interventions as part of a multidisciplinary approach would be beneficial in the experience of chronic back pain.

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A narrative review of the importance of pharmacokinetics and drug-drug interactions of preventive therapies in migraine management.

To review the pharmacokinetics of major classes of migraine preventives and the clinical implications of drug-drug interactions (DDIs) with the use of these therapies in migraine management.

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