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Risk-factor identification related to chronic opioid use after surgery may facilitate interventions mitigating postoperative opioid consumption. We evaluated the relationship between opioid use preceding total hip arthroplasty (THA) and total knee arthroplasty (TKA), and chronic use postoperatively, and the risk of chronic opioid use after total joint arthroplasty.
Learn More >In most experimental studies in which verbal suggestion and classical conditioning are implemented together to induce placebo effects, the former precedes the latter. In naturally occurring situations, however, the information concerning pain does not always precede but often follows the pain experience. Moreover, this information is not always congruent with experience. This study investigates whether the chronology of verbal suggestion and conditioning, as well as their congruence, affects placebo hypoalgesia and nocebo hyperalgesia. The effects induced in 15 groups were compared. The participants in 8 experimental groups were presented with verbal suggestions that were either congruent or incongruent with classical conditioning. The verbal suggestions were provided either before or after conditioning. In 2 other experimental groups, placebo conditioning or nocebo conditioning was implemented without any verbal suggestion; in 2 groups, verbal suggestion of hypoalgesia or hyperalgesia without conditioning was applied. The control groups without any suggestions or conditioning were also included. Placebo hypoalgesia induced by congruent procedures was significantly stronger when the suggestion of hypoalgesia preceded rather than followed conditioning. The order of the congruent procedures did not affect the magnitude of nocebo hyperalgesia. In the groups in which incongruent procedures were implemented, placebo hypoalgesia or nocebo hyperalgesia was in line with the direction of the last-used procedure, regardless of whether it was conditioning or verbal suggestion. The results show that not the type of the procedure (verbal suggestion or conditioning), but the direction of the last-used procedure shapes pain-related expectancies and determines placebo effects.
Learn More >Pain is the primary motivation for seeking medical care. Although pain may subside as inflammation resolves or an injury heals, it is increasingly evident that persistency of the pain state can occur with significant regularity. Chronic pain requires aggressive management to minimize its physiological consequences and diminish its impact on quality of life. Although opioids commonly are prescribed for intractable pain, concerns regarding reduced efficacy, as well as risks of tolerance and dependence, misuse, diversion, and overdose mortality rates limit their utility. Advances in development of nonopioid interventions hinge on our appreciation of underlying mechanisms of pain hypersensitivity. For instance, the contributory role of immunity and the associated presence of autoimmune syndromes has become of particular interest. Males and females exhibit fundamental differences in innate and adaptive immune responses, some of which are present throughout life, whereas others manifest with reproductive maturation. In general, the incidence of chronic pain conditions, particularly those with likely autoimmune covariates, is significantly higher in women. Accordingly, evidence is now accruing in support of neuroimmune interactions driving sex differences in the development and maintenance of pain hypersensitivity and chronicity. This review highlights known sexual dimorphisms of neuroimmune signaling in pain states modeled in rodents, which may yield potential high-value sex-specific targets to inform future analgesic drug discovery efforts.
Learn More >Dermatitis encompasses a spectrum of inflammatory skin disorders with aberrant immune responses classified as type 1, type 2, and/or type 3. Major advances in the understanding of the pathogenesis of atopic dermatitis (AD) have shed new light on how innate immune responses critically regulate type 2 inflammation and itch. This article highlights the diverse ways by which type 2 immune cells regulate diseases beyond AD. The discovery of human Mas-related G protein-coupled receptor X2 on mast cells has revealed novel T cell-independent and immunoglobulin E-independent mechanisms of allergic contact dermatitis-associated and urticarial itch, respectively.
Learn More >Gentle touch such as stroking of the skin produces a pleasant feeling, which is detected by a rare subset of sensory neurons that express Mas-related G protein-coupled receptor B4 (MrgprB4) in mice. We examined small populations of MrgprB4-positive neurons in the trigeminal ganglion and the dorsal root ganglion, and most of these were sensitive to transient receptor potential ankyrin 1 (TRPA1) agonist but not TRPV1, TRPM8, or TRPV4 agonists. Deficiency of MrgprB4 did not affect noxious pain or itch behaviors in the hairless plantar and hairy cheek. Although behavior related to acetone-induced cold sensing in the hind paw was not changed, unpleasant sensory behaviors in response to acetone application or sucrose splash to the cheek were significantly enhanced in Mrgprb4-knockout mice as well as in TRPA1-knockout mice. These results suggest that MrgprB4 in the trigeminal neurons produces pleasant sensations in cooperation with TRPA1, rather than noxious or cold sensations. Pleasant sensations may modulate unpleasant sensations on the cheek via MrgprB4.
Learn More >Research suggests that endogenous opioids play a key role in the creation and maintenance of attachment bonds. Opioids acting at the μ-opioid receptor mediate reward and analgesia and are thus thought to underlie feelings of comfort and warmth experienced in the presence of close others. Disruption of μ-opioidergic activity increases separation distress in animals, suggesting that low opioid states may contribute to social pain. Accordingly, a functional μ-opioid receptor (OPRM1) polymorphism (C77G in primates, A118G in humans) affecting opioidergic signaling has been associated with separation distress and attachment behavior in nonhuman primates, and social pain sensitivity in humans. However, no research has examined the effects of this polymorphism on socioemotional experience, and specifically felt security, in daily interactions between romantic partners. Using an event-contingent recording method, members of 92 cohabiting romantic couples reported their felt security and quarrelsome behavior in daily interactions with each other for 20 days. Consistent with prior work, findings suggested that, relative to AA homozygotes, G allele carriers were more sensitive to their partners' self-reported quarrelsome behaviors (e.g., criticism), showing a greater decline in felt security when their partners reported higher quarrelsome behavior than usual. This is the first study to link variation in OPRM1 with felt security toward romantic partners in everyday social interactions. More generally, this research supports the theory that the attachment system incorporated evolutionarily primitive pain-regulating opioidergic pathways. We also discuss implications of this work for understanding of differential vulnerability to health risks posed by social stress.
Learn More >Chronic low back pain (CLBP) is a highly prevalent and significant cause of disability which is often resistant to pharmacological management. Virtual reality (VR) is an emerging technology with the potential to influence CLBP, and has been suggested as an alternative to opioids for pain management. VR is a goalfocused, computer-simulated reality allowing modification of the user's experience of their perceived world. A narrative review of peer-reviewed literature using a systematic search strategy, and sole reviewer for data extraction. VR has demonstrated effectiveness in reducing acute, experimental and chronic pain. This review describes the theoretical basis of the therapeutic effects of VR on CLBP via three distinct mechanisms: distraction, neuromodulation and graded exposure therapy. Furthermore, clinical application will be considered, including discussion of ethical issues associated with the technology.Implications for rehabilitationVirtual reality (VR) is suggested as an alternative for opioids in the management of acute and chronic pain.The therapeutic mechanisms of VR in chronic low back pain (CLBP) are equivocal but include distraction, neuromodulation of body perception and graded exposure therapy.VR may show greater efficacy in patients with CLBP with associated kinesiophobia.VR may show greater effect with increased immersion.
Learn More >Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. Adult moderate-to-severe AD patients, referring to 39 Italian centres, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). A total of 109 (71M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.
Learn More >Neuropathic pain is a debilitating consequence of spinal cord injury. Ecological momentary assessment can be a valuable research tool for understanding temporal fluctuations in neuropathic pain and designing effective management strategies. The objectives of this study were to (a) describe strategies necessary to adapt ecological momentary assessment to measure neuropathic pain in adults with spinal cord injury, and (b) explore participant perceptions of using ecological momentary assessment to measure pain sensations. End-users with spinal cord injury provided input to guide development of an ecological momentary assessment protocol. Six adults with spinal cord injury (ages 27-50 years, = 39.33 ± 8.24) engaged in the six-day protocol and completed six daily neuropathic pain assessments. Upon finishing participants completed a semi-structured interview regarding their protocol experiences. A qualitative content analysis was used to analyze the interview data. Participants reported that this specific ecological momentary assessment protocol was unobtrusive to their daily routines, and effectively captured their neuropathic pain sensations. However, participants experienced increased neuropathic pain due to the repeated nature of assessments. Ecological momentary assessment can capture the dynamic nature of neuropathic pain experienced by persons with spinal cord injury. However, caution should be taken when designing intensive pain-related protocols to minimize pain exacerbation.IMPLICATIONS FOR REHABILITATIONNeuropathic pain affects up to 75% of people with spinal cord injury and is one of the most frequently occurring, debilitating forms of pain.Appropriate and feasible pain data collection methods are necessary to acquire a better understanding of how neuropathic pain manifests in people with spinal cord injury.Implementing ecological momentary assessment in a rehabilitation setting may help facilitate the monitoring of neuropathic pain for both rehabilitation professionals and persons with SCI.Using ecological momentary assessment may lead to a better understanding of individual temporal patterns of neuropathic pain that could inform the design of tailored neuropathic pain management techniques.
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