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The opioid epidemic is a major public health issue in the United States. Exposure of opioid naïve-patients to opioids in the perioperative period is a well-documented source of continued use with one in 20 opioid-naïve surgical patients continuing to use opioids beyond 90 days. There is no association with magnitude of surgery, major versus minor, and the strongest predictor of continued use is surgical exposure. Causal factors include over reliance on opioids for intraoperative and postoperative analgesia and excessive ambulatory opioid prescribing. Opioid-induced hyperalgesia can paradoxically result from intraoperative (anesthesia controlled) opioid administration. Increasing size of initial prescription is a strong predictor of continued use necessitating procedure specific supplies limited to under 3-days. Alternative multimodal pain management (non-opioid medications and regional anesthesia) that limit opioid use must be a high priority with opioids reserved for severe breakthrough pain. Barriers to implementation of opioid-sparing pathways include reluctance to adopt protocols and apprehension about opioid elimination. Considering the number of surgeries performed annually in the United States, perioperative physicians must aggressively address modifiable factors in surgical patients. Patient care pathways need to be constructed collaboratively by surgeons and anesthesiologists with continuing feedback to optimize patient outcomes including iatrogenic opioid dependence.
Learn More >The need for measuring emotional functioning in chronic pain patients was recognized decades ago. The Initiative on Methods, Measures, and Pain Assessment in Clinical Trials (IMMPACT) proposed the Profile of Mood States (POMS) for this purpose. However, to date, its factor structure has not been confirmed in these patients.
Learn More >Atopic dermatitis (AD) patients have heterogeneous clinical phenotypes, including different combinations of itch and lesional severity. Little is known about the characteristics and course of these subtypes.
Learn More >Adverse childhood experiences (ACEs) are commonly observed in the general population and often have lasting neurological and physiological effects. Previous studies have found links between exposure to ACEs, headaches, and functional difficulties in adults. However, little is known about the mechanisms through which exposure to ACEs is associated with headaches among children.
Learn More >To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression.
Learn More >Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB receptor agonist ABK5.
Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB and CB, and Δ-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caused by activation of CB, but not CB. ABK5 is a CB subtype selective agonist that has a very different structure from known cannabinoid receptor agonists. Here, we report anti-inflammatory effects of ABK5 using the T-cell line Jurkat cells, and antinociceptive effect in an inflammatory pain model in rats. Production of the cytokines IL-2 and TNF-α was measured in stimulated Jurkat cells and MOLT-4 cells, and CXCL12-mediated chemotaxis of Jurkat cells was evaluated by a transwell migration assay. Anti-inflammatory and antinociceptive effects of ABK5 were also evaluated in a hindpaw CFA model in rats. ABK5 significantly decreased production of IL-2 and TNF-α measured as both mRNA and protein levels, and reduced chemotaxis towards CXCL12. It also attenuated edema and increased mechanical threshold in the hindpaw of CFA-treated rats. These results suggest that ABK5 is a good lead compound for the development of potential anti-inflammatory and analgesic agents.
Learn More >Determining long-term trends in chronic pain prevalence is critical for evaluating and shaping U.S. health policies, but little research has examined such trends. This study (1) provides estimates of pain trends among U.S. adults across major population groups; (2) tests whether sociodemographic disparities in pain have widened or narrowed over time; and (3) examines socioeconomic, behavioral, psychological, and medical correlates of pain trends. Regression and decomposition analyses of joint, low back, neck, facial/jaw pain, and headache/migraine using the 2002-2018 National Health Interview Survey for adults aged 25-84 (N = 441,707) assess the trends and their correlates. We find extensive escalation of pain prevalence in all population subgroups: overall, reports of pain in at least one site increased by 10%, representing an additional 10.5 million adults experiencing pain. Socioeconomic disparities in pain are widening over time, and psychological distress and health behaviors are among the salient correlates of the trends. This study thus comprehensively documents rising pain prevalence among Americans across the adult life span and highlights socioeconomic, behavioral, and psychological factors as important correlates of the trends. Chronic pain is an important dimension of population health, and demographic research should include it when studying health and health disparities.
Learn More >Mechanical allodynia is a painful perception of mechanical stimuli and one of the typical symptoms in bone cancer pain (BCP). Previous studies have revealed that mice and humans lacking mechanically activated Piezo2 channels do not sense mechanical stimuli. However, the underlying mechanism of Piezo2 in BCP has not been well established. The aim of the present study was to investigate whether exchange protein directly activated by cAMP 1 (Epac1) mediated Piezo2 signaling pathway may be responsible for the mechanical allodynia of BCP and whether N-methyl-D-aspartic acid (NMDA) receptor subunit 2B (NR2B) is involved in the pathway. In the present study, a BCP model was established in C3H/HeJ mice by intramedullary injection of osteosarcoma cells. The results of the mechanical allodynia test demonstrated a markedly decreased paw withdrawal mechanical threshold in BCP mice, accompanied by a significant increase in Epac1, NR2B proteins and Piezo2 mRNA expression levels in the ipsilateral dorsal root ganglion (DRG). Compared with the sham group, intrathecal Epac1 antisense oligodeoxynucleotides (Epac1-ASODN) effectively ameliorated the mechanical allodynia and decreased the expression levels of NR2B and Piezo2 in the tumor group. Pretreatment of naïve mice with a NR2B antagonist prevented the aggravation of mechanical allodynia and DRG Piezo2 levels induced by an Epac1 agonist. However, the NR2B agonist-induced increase in Piezo2 expression levels was not reversed by pretreatment with Epac1-ASODN. In conclusion, the results of the present study demonstrated that NR2B, which is a crucial downstream regulator of Epac1, may mediate the Epac1-Piezo2 pathway contributing to the development of the mechanical allodynia of BCP. The present study may enrich the theoretical knowledge of the mechanical allodynia of BCP and provide a potential analgesic strategy for clinical treatment.
Learn More >Opioid use disorder (OUD) is a debilitating disorder that affects millions of people. Neutral cues can acquire motivational properties when paired with the positive emotional effects of drug intoxication to stimulate relapse. However, much less research has been devoted to cues that become conditioned to the aversive effects of opioid withdrawal. We argue that environmental stimuli promote motivation for opioids when cues are paired with withdrawal (conditioned withdrawal) and generate opioid consumption to terminate conditioned withdrawal (conditioned negative reinforcement). We review evidence that cues associated with pain drive opioid consumption, as patients with chronic pain may misuse opioids to escape physical and emotional pain. We highlight sex differences in withdrawal-induced stress reactivity and withdrawal cue processing and discuss neurocircuitry that may underlie withdrawal cue processing in dependent individuals. These studies highlight the importance of studying cues associated with withdrawal in dependent individuals and point to areas for exploration in OUD research.
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