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Expectancies for pain and pain relief are central to experimental models of placebo analgesia and nocebo hyperalgesia, and are a promising target for clinical intervention in patients with chronic pain. Affective states may play an important role in modulating the degree to which expectancies influence pain, broadening the opportunities for intervention targets. However, findings to date have been mixed and mostly limited to laboratory designs. Few studies have examined the interplay of naturally occurring affective states, pain expectancies, and pain experiences in the course of daily life with chronic pain. In the present study, patients with temporomandibular disorder reported their daily pain expectancies and affective states each morning, and their daily pain experience each evening, over a two-week period. Multilevel modeling analyses revealed the association of morning pain expectancies with subsequent pain experiences was moderated by morning positive affective state (B=.04, SE=.02, t=2.00, p=.046), such that the congruent assimilation of a low pain expectancy with a low pain experience was starkest when morning positive affect was higher than usual. Relatedly, higher morning positive affect predicted greater odds of experiencing a match between pain expectancies and pain experience when the expectation was for low, but not high, pain levels (OR: 1.19, CI: 1.01-1.41, p=.03). Negative affect, in contrast, did not significantly influence the assimilation of high pain expectancies with high pain experiences. These findings extend prior experimental studies by showing that the association of daily pain expectancies with pain experience varies as a function of affective state.
Learn More >Recent studies suggest that the COVID-19 pandemic can serve as a unique psychosocial stressor that can negatively impact individuals with chronic pain. Using a large online sample in the U.S., the present study sought to investigate the impact of the pandemic on the trajectories of pain severity and interference, emotional distress (i.e., anxiety and depressive symptoms), and opioid misuse behaviors across one year. Potential moderating effects of socio-demographic factors and individual differences in pain catastrophizing, pain acceptance, and sleep disturbance on outcome trajectories were also examined. Adults with chronic pain were surveyed three times across one year (April/May 2020 [N=1,453]; June/July 2020 [N=878], and May 2021 [N=813]) via Amazon's Mechanical Turk online crowdsourcing platform. Mixed-effects growth models revealed that pain severity and interference, emotional distress, and opioid misuse behaviors did not significantly deteriorate across one year during the pandemic. None of the socio-demographic factors, pain catastrophizing, or sleep disturbance moderated outcome trajectories. However, individuals with higher pain acceptance reported greater improvement in pain severity (p< .008, 95% CI: -.0002, -.00004) and depressive symptoms (p< .001, 95% CI: -.001, -.0004) over time. Our findings suggest that the negative impact of the pandemic on pain, emotional distress, and opioid misuse behaviors is quite small overall. The outcome trajectories were also stable across different socio-demographic factors, as well as individual differences in pain catastrophizing and sleep disturbance. Nevertheless, interventions that target improvement of pain acceptance may help individuals with chronic pain be resilient during the pandemic.
Learn More >The role of the trigeminal system in facial and dural sensitivity has been recognized for a long time. More recently, the trigeminal system has also been considered a prominent actor in brain nociceptive innervation. It is the anatomical substrate of several frequent conditions, such as primary or secondary headaches, trigeminal neuralgia, and other orofacial pains. Appreciation of the delicate anatomical arrangement of the trigeminal pathway is one of the keys to understanding these conditions' pathophysiology and to proposing innovative treatments. This review provides a structured presentation of existing knowledge about the trigeminal system, from classical anatomical data to the most recent literature. First, we present the organization of the trigeminal pathway from the trigeminal divisions, nerve, and nuclei to the thalamus and somatosensory cortex. We describe the neurons and fibers' repartition at each level, depending on the location (somatotopic organization) and the type of receptors (modal organization). Such a dual somatotopic-modal arrangement of the trigeminal fibers is especially clear for the juxtapontine segment of the trigeminal nerve and the trigeminal nuclei of the brainstem. It has significant clinical consequences both for diagnosis and treatment. Second, we explore how the trigeminal system is modulated and involved in reflexes, for instance the trigemino-cardiac and the trigemino-autonomic reflexes, which could play an essential role in the autonomic symptoms observed in cluster headache. Finally, we present how to interact with this complex system to relieve pain mediated by the trigeminal system. This section covers both neuromodulatory and lesional approaches.
Learn More >With the change in lifestyle and aging of the population, osteoarthritis (OA) is emerging as a major medical burden globally. OA is a chronic inflammatory and degenerative disease initially manifesting with joint pain and eventually leading to permanent disability. To date, there are no drugs available for the definitive treatment of osteoarthritis and most therapies have been palliative in nature by alleviating symptoms rather than curing the disease. This coupled with the vague understanding of the early symptoms and methods of diagnosis so that the disease continues as a global problem and calls for concerted research efforts. A cascade of events regulates the onset and progression of osteoarthritis starting with the production of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α; catabolic enzymes, such as matrix metalloproteinases (MMPs)-1, -3, and -13, culminating into cartilage breakdown, loss of lubrication, pain, and inability to load the joint. Although intra-articular injections of small and macromolecules are often prescribed to alleviate symptoms, low residence times within the synovial cavity severely impair their efficacy. This review will briefly describe the factors dictating the onset and progression of the disease, present the current clinically approved methods for its treatment and diagnosis, and finally elaborate on the main challenges and opportunities for the application of nano/micromedicines in the treatment of osteoarthritis. Thus, future treatment regimens will benefit from simultaneous consideration of the mechanobiological, the inflammatory, and tissue degradation aspects of the disease. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.
Learn More >The search for safe and efficient chronic pain treatments is dampened by the lack of reliable models that faithfully reproduce current pharmacological treatments for chronic spontaneous pain in humans. Preclinical models often assess the antinociceptive efficacy of non-contingent pharmacological treatments evaluated in the short-term. Here, we provide a protocol of contingent operant self-medication in mice, which allows the estimation of spontaneous pain relief and drug abuse liability in models of persistent pain. This paradigm requires preliminary habituation and animal handling, followed by training of mice in operant conditioning boxes, to allow subsequent analgesic drug self-administration. After the initial acquisition of food-maintained operant behavior, a chronic pain sensitization is induced. Posterior intravenous jugular catheterization and coupling of operant conditioning boxes to perfusion pumps allow quantification of operant responding for intravenous drug self-administration. All mice show an initial operant drug self-administration behavior associated with the previous food-maintained operant training. This initial operant responding is extinguished after administration of ineffective treatments, but continues when the compounds have analgesic efficacy or intrinsic reinforcing properties. The identification of a significant drug self-administration selectively expressed in mice exposed to the chronic pain condition is indicative of analgesic drug effects, whereas persistent self-administration in control mice is indicative of abuse liability. The present protocol provides the behavioral and surgical procedures needed to assess spontaneous pain relief and potential for abuse of pharmacological treatments, through contingent analgesic self-medication in mice. Graphic abstract: Animals are subjected to a 5-day food self-administration protocol with a fixed ratio of reinforcement of 1 (FR1, 1 interaction with the active nose-poke causes the release of 1 reinforcer/infusion), to acquire the operant behavior. After this training, mice are subjected to the chronic pain or sham procedure, and four days later an intravenous (i.v.) catheterization is performed, to allow self-administration with the selected compound or its vehicle. Three days after the catheterization, animals start the drug/vehicle self-administration protocol at FR1. The patency of the catheter is evaluated with the thiopental test after the last self-administration session. Adapted from Bura (2018).
Learn More >Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The processing of pain involves complicated modulation at the levels of the periphery, spinal cord, and brain. The pathogenesis of chronic pain is still not fully understood, which makes the clinical treatment challenging. Optogenetics, which combines optical and genetic technologies, can precisely intervene in the activity of specific groups of neurons and elements of the related circuits. Taking advantage of optogenetics, researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission, pain modulation, and chronic pain both in the periphery and the central nervous system. In this review, we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.
Learn More >It is important to find effective and safe pharmacological options for managing cluster headache (CH) because there is limited evidence from studies supporting the general efficacy and safety of pharmacological therapies. This systematic review and network meta-analysis (NMA) analyzed published randomized controlled trials (RCTs) to evaluate the efficacy and safety of pharmacological treatments in patients with CH. The PubMed and Embase databases were searched to identify RCTs that evaluated the efficacy and safety of pharmacological treatments for CH. Efficacy outcomes included frequency and duration of attacks, pain-free rate, and the use of rescue agents. Safety outcomes were evaluated based on the number of patients who experienced adverse events. A total of 23 studies were included in the analysis. The frequency of attacks was reduced (mean difference (MD) = -1.05, 95% confidence interval (CI) = -1.62 to -0.47; = 0.0004), and the pain-free rate was increased (odds ratio (OR) = 3.89, 95% CI = 2.76-5.48; < 0.00001) in the pharmacological treatment group, with a lower frequency of rescue agent use than the placebo group. Preventive, acute, and triptan or non-triptan therapies did not show significant differences in efficacy ( > 0.05). In the NMA, different results were shown among the interventions; for example, zolmitriptan 5 mg was more effective than zolmitriptan 10 mg in the pain-free outcome (OR = 0.40, 95% CI = 0.19-0.82; < 0.05). Pharmacological treatment was shown to be more effective than placebo to manage CH with differences among types of therapies and individual interventions, and it was consistently shown to be associated with the development of adverse events. Thus, individualized therapy approaches should be applied to treat CH in real-world practice.
Learn More >Our previous work has shown that somatostatin effectively inhibits neuropathic pain by activating its type 2 receptor (SSTR2) in the dorsal root ganglion (DRG) and spinal cord of mice. However, the underlying mechanism of this activation has not been elucidated.
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