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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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >Trials of Cognitive Therapy (CT), Mindfulness-Based Stress Reduction (MBSR), and Behavior Therapy (BT) suggest that all three treatments produce reductions in pain and improvements in physical function, mood and sleep disturbance in people with chronic pain conditions. Fewer studies have compared the relative efficacies of these treatments. In this randomized controlled study, we compared CT, MBSR, BT and treatment as usual (TAU) in a sample of people with chronic low back pain (N = 521). Eight individual sessions were administered with weekly assessments of outcomes. Consistent with prior work, we found that CT, MBSR, and BT produced similar pre- to post-treatment effects on all outcomes and revealed similar levels of maintenance of treatment gains at 6-month follow-up. All three active treatments produced greater improvements than TAU. Weekly assessments allowed us to assess rates of change; i.e., how quickly a given treatment produced significant differences, compared to TAU, on a given outcome. The three treatments differed significantly from TAU on average by session 6, and this rate of treatment effect was consistent across all treatments. Results suggest the possibility that the specific techniques included in CT, MBSR, and BT may be less important for producing benefits than people participating in any techniques rooted in these evidence-based psychosocial treatments for chronic pain.
Learn More >Because many persons living with chronic pain achieve a relatively balanced lifestyle without experiencing functional disability, medical psychologists must explain the well-documented co-occurrence of pain complaints and DSM-5-disorders (including but not limited to depression and anxiety) in a significant subset of individuals. The question of differential resilience versus susceptibility has received modest theoretical and empirical attention, but remains open. In this review, I deconstruct the temporally extended pain adaptation process in order to address this vexing question, relying upon two complementary explanatory frames. The first is a motivational/cybernetic systems formulation labeled the Goal-Centered, Self-Regulatory, Automated Social Systems Psychology (GRASSP) model, erected upon feedback sensitive, goal-guided, hierarchically organized self-regulatory processes. Depression and anxiety presumably result from compromised regulatory functions undermining pain processing, goal pursuit, and everyday performance. The second perspective postulates a "Bayesian Brain"/"Predictive Mind" capable of unifying perception, action, and emotion via predictive processing. From a Bayesian perspective, predictive processing implies that our brains evolved to compare, without conscious direction, incoming environmental information against prior, model-based predictions in order to arrive at accurate perceptual representations of the world. Maladjustment results from failures of active inference. When applied to the perception of visceral information, the embodied process, termed interoceptive inference, can also yield pathogenic outcomes. The Bayesian model holds that depression and anxiety in individuals with pain result from error-prone (biased, rigid, or highly certain) prior evaluations of aversive feeling states and their relation to the external milieu. I consider how the hybrid conceptual framework advanced by the two models points to several novel and familiar avenues of intervention.
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