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Depression, fatigue, and pain commonly co-occur in multiple sclerosis (MS) and are positively associated with one another. However, it is unclear whether treatment-related improvement in one of these symptoms is associated with improvements in the other two symptoms.
Learn More >Meditation has been shown to improve outcomes for chronic pain by increasing patients' awareness of their own bodies. Some patients have an innate ability to leverage their mind-body connection, and this interoceptive awareness may aid them in garnering pain relief. We explored whether spinal cord stimulation (SCS) patients with greater innate awareness had better outcomes.
Learn More >Chronic pain is a significant comorbid condition among individuals with opioid use disorder (OUD). However, due to conflicting perceptions of responsibility, structural barriers, and a lack of widely applied standards of care, it is unclear what the landscape of chronic pain management looks like in addiction medicine. Using a national opioid surveillance system, we analyzed survey data from new entrants (n=14,449) to 225 OUD treatment centers from 2013 to 2018, as well as an online survey among a subset of respondents (n=309). While chronic pain was reported by 33.4% of the sample, two-thirds of the chronic pain group (66.0%) reported their pain was not managed through their OUD treatment program, with 47% reporting worsening pain. Pain that was managed was primarily done so through pharmaceuticals (75.2%), notably as a secondary effect of medication-assisted treatment. In addition, 43.2% reported chronic pain as a primary factor in their opioid relapse. These data suggest that chronic pain is commonly reported, yet not managed by many OUD treatment programs, increasing the likelihood of opioid relapse. In order to improve poor outcomes among OUD patients, interdisciplinary collaboration/care, along with evidence-based policies or processes for quality pain management in addiction care need to be prioritized. Perspective: This article suggests chronic pain is commonly reported, yet not managed by many OUD treatment programs, increasing the likelihood of opioid relapse. In order to improve low retention and success rates among OUD patients, interdisciplinary collaboration, evidence-based policies or processes (e.g., referral) for quality pain management in addiction care need to be prioritized.
Learn More >Chronic pain (CP) and cognitive decline (CD) are costly, challenging to treat, highly prevalent among older adults, and worsen each other over time. We are iteratively developing Active-Brains-Fitbit (AB-F), a live video program for older adults with CP and CD that teaches mind-body skills and gradual increases in step count aided by a Fitbit. AB-F has demonstrated feasibility, acceptability, and signals of improvement in emotional, physical, and cognitive function when delivered in-person to this population.
Learn More >While the prognosis of patients with Ewing sarcoma (EwS) is improving, little is known about the frequency of pain and its risk factors in survivors of EwS. This study aims to analyse the prevalence and risk factors of pain and its predictive value for recurrence.
Learn More >Partner's responses to pain behaviours play a pivotal role in the patient's adjustment. This study aims to further our knowledge regarding patients' and partners' interpretation of partners' responses to pain behaviours, and the possible discrepancies between patients' and partners' perceptions. Further, this study examines patients' preferred responses to pain behaviours and possible discrepancies between received and preferred responses to pain behaviours.
Learn More >Peripheral denervation and pain are hallmarks of small fiber neuropathy (SFN). We investigated the contribution of skin cells on nociceptor degeneration and sensitization. We recruited 56 patients with SFN and 31 healthy controls, and collected skin punch biopsies for immunohistochemical and immunocytochemical analysis of netrin-1 (NTN1) and pro- and anti-inflammatory cytokine expression patterns. We further applied co-culture systems with murine dorsal root ganglion (DRG) neurons for skin cell-nerve interaction studies and patch-clamp analysis. Human keratinocytes attract murine DRG neuron neurites and the gene expression of the axon guidance cue NTN1 is higher in keratinocytes of SFN patients than in controls. NTN1 slows and reduces murine sensory neurite outgrowth in vitro, but does not alter keratinocyte cytokine expression. In the naïve state, keratinocytes of SFN patients show a higher expression of transforming growth factor-β1 (p<0.05), while fibroblasts display higher expression of the algesic cytokines interleukin (IL)-6 (p<0.01) and IL-8 (p<0.05). IL-6 incubation of murine DRG neurons leads to an increase in action potential firing rates compared to baseline (p<0.01). Our data provide evidence for a differential effect of keratinocytes and fibroblasts on nociceptor degeneration and sensitization in SFN compared to healthy controls and further supports the concept of cutaneous nociception.
Learn More >Cluster headache (CH) is a highly disabling primary headache disorder. To date, characterization of outcomes in the preventive treatment of episodic CH, including precise definitions of clinically meaningful attack frequency reduction and impact on acute treatment management, is lacking.
Learn More >Many primary care clinics are resistant to accept new patients taking prescription opioids for chronic pain. It is unclear how much of this practice is specific to individuals who may be perceived to have aberrant opioid use. This study sought to determine whether clinics are more or less willing to accept and prescribe opioids to patients depending on whether their history is more or less suggestive of aberrant opioids use by conducting an audit survey of primary care clinics in 9 states from May to July 2019. Simulated patients taking opioids for chronic pain called each clinic twice, giving one of two scenarios for needing a new provider: their previous physician had either 1) retired or 2) stopped prescribing opioids for unspecified reasons. Clinic willingness to continue prescribing opioids and accept the patient for general primary care were assessed. Of 452 clinics responding to both scenarios (904 calls), 193 (43%) said their providers would not prescribe opioids in either scenario, 146 (32%) said their providers might prescribe in both, and 113 (25%) responded differently to each scenario. Clinics responding differently had greater odds (OR=1.83 CI[1.23,2.76]) of willingness to prescribe when the previous doctor retired than when the doctor had stopped prescribing. These findings suggest that primary care access is limited for patients taking opioids for chronic pain, and differentially further reduced for patients whose histories are suggestive of aberrant use. This denial of care could lead to unintended harms such as worsened pain or conversion to illicit substances.
Learn More >Among the five KCNQ channels, also known as the K7 voltage-gated potassium (K) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological disorders such as epilepsy, deafness, and neuropathic pain. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 and its complexes with the opener retigabine or the blocker linopirdine at overall resolutions of 2.5, 3.1, and 3.3 Å, respectively. In all structures, a phosphatidylinositol 4,5-bisphosphate (PIP) molecule inserts its head group into a cavity within each voltage-sensing domain (VSD), revealing an unobserved binding mode for PIP. Retigabine nestles in each fenestration, inducing local shifts. Instead of staying within the central pore, linopirdine resides in a cytosolic cavity underneath the inner gate. Electrophysiological analyses of various mutants corroborated the structural observations. Our studies reveal the molecular basis for the modulatory mechanism of neuronal KCNQ channels and provide a framework for structure-facilitated drug discovery targeting these important channels.
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