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Chronic pain and substance use disorders are serious conditions that are prevalent among homeless populations. The aim of this study was to examine the association between chronic pain and substance use among individuals experiencing homelessness and mental illness. We analyzed cross-sectional data from two sites of the At Home/Chez Soi study (Vancouver and Toronto) using bivariate statistics and multivariate logistic regression. Substance use and chronic pain parameters were assessed with the Maudsley Addiction Profile and purpose-designed short instruments. The sample comprised 828 participants. Mean age was 42.4 years and 54% reported chronic pain. In bivariate analysis, chronic pain was significantly associated with use of opioids and stimulants, daily substance use, polysubstance use and injecting as route of administration. In multivariate analysis, only daily substance use (OR: 1.46, 95% CI: 1.02-2.09) and injecting (OR: 1.81, 95% CI: 1.08-3.05) remained as significant associated factors, whereas neither use of opioids nor use of stimulants specifically were significantly associated with chronic pain. Among participants with chronic pain, daily substance users (50% vs. 22%, < 0.001) and injectors (66% vs. 24%, < 0.001) were more likely to use non-prescribed medication for pain. Participants with daily substance use were less likely to receive professional treatment (52% vs. 64%, = 0.017) and prescribed pain medication (42% vs. 54%, = 0.023). Our findings suggest an association of chronic pain with patterns related to severity of substance use rather than to specific substance use in homeless persons with mental illness. Interventions aiming at prevention and treatment of chronic pain in this population should consider severity of substance use and associated risk behavior over use of specific substances.
Learn More >Pyridoxine (vitamin B6) toxicity is known to cause a length-dependent, sensory predominant axonal polyneuropathy. There is debate regarding the threshold at which intake levels can cause neurological symptoms through pyridoxine toxicity. We asked if elevated plasma vitamin B6 levels were related to outcome measures in a well-characterized cohort of patients with chronic idiopathic axonal polyneuropathy (CIAP).
Learn More >While opioids produce both analgesia and side-effects by action at mu-opioid receptors (MOR), at spinal and supraspinal sites, potency of different opioids to produce these effects vary. While it has been suggested that these differences might be due to bias for signaling via β-arrestin versus G protein alpha (Gα), recent studies suggest that G protein biased MOR agonists still produce clinically important side-effects. Since bias also exists in the role of Gα subunits, we evaluated the role of Gα subunits in analgesia, hyperalgesia, and hyperalgesic priming produced by fentanyl and morphine, in male rats. We found that intrathecal treatment with oligodeoxynucleotides antisense (AS-ODN) for Gα2, Gα3 and Gα markedly attenuated hyperalgesia induced by sub-analgesic dose (sub-AD) fentanyl, while AS-ODN for Gα1, as well as Gα2 and Gα3, but not Gα, prevented hyperalgesia induced by sub-AD morphine. AS-ODN for Gα1 and Gα2 unexpectedly analgesia induced by analgesic dose (AD) fentanyl, while Gα1 AS-ODN markedly AD morphine analgesia. Hyperalgesic priming, assessed by prolongation of prostaglandin E (PGE)-induced hyperalgesia, was not produced by systemic sub-AD and AD fentanyl in Gα3 and Gα AS-ODN-treated rats, respectively. In contrast, none of the Gα AS-ODNs tested affected priming induced by systemic sub-AD and AD morphine. We conclude that signaling by different Gα subunits is necessary for the analgesia and side-effects of two of the most clinically used opioid analgesics. Design of opioid analgesics that demonstrate selectivity for individual Gα may produce a more limited range of side-effects and enhanced analgesia. Biased mu-opioid receptor (MOR) agonists that preferentially signal through G proteins α-subunits over β-arrestins have been developed, as an approach to mitigate opioid side-effects. However, we recently demonstrated that biased MOR agonists also produce hyperalgesia and priming. We show that oligodeoxynucleotide antisense (AS-ODN) to different Gα subunits play a role in hyperalgesia and analgesia induced by sub-analgesic and analgesic dose (respectively), of fentanyl and morphine, as well as in priming. Our findings have the potential to advance our understanding of the mechanisms involved in adverse effects of opioid analgesics that could assist in the development of novel analgesics, preferentially targeting specific G protein α-subunits.
Learn More >Persistent postsurgical pain (PPSP) is a common complication that impacts quality of life, often necessitating long-term opioid treatment. Certain neurocognitive factors, including reduced performance on cognitive flexibility tasks, are associated with increased risk for PPSP. We examine perceptions of surgical patients and clinicians regarding perioperative pain management activities and needs; patient acceptance and use of a perioperative neurocognitive training intervention; and implementation feasibility.
Learn More >Patients with back pain comprise a large proportion of the outpatient practice among physiatrists. Diagnostic tools are limited to clinical history, physical examinations and imaging. Non-surgical treatments are largely empirical, encompassing medications, physical therapy, manual treatments and interventional spinal procedures. A body of literature is emerging confirming elevated levels of biomarkers including inflammatory cytokines in patients with back pain and/or radiculopathy, largely because the protein assay sensitivity has increased. These biomarkers may serve as tool to assist diagnosis and assess outcomes.The presence of inflammatory mediators in the intervertebral disc tissues and blood helped confirming the inflammatory underpinnings of back pain related to intervertebral disc degeneration. Literature reviewed here suggests that biomarkers could assist clinical diagnosis and monitor physiological outcomes during and following treatments for spine related pain. Biomarkers must be measured in a large and diverse asymptomatic population, in the context of age and comorbidities to prevent false positive tests. These levels can then be rationally compared to those in patients with back disorders including discogenic back pain, radiculopathy and spinal stenosis. While studies reviewed here used "candidate marker" approaches, future non-biased approaches in clearly defined patient populations could uncover novel biomarkers in clinical management of patients.
Learn More >To assess risk factors for persistent neuropathic pain in subjects recovered from COVID-19 and to study the serum level of neurofilament light chain (NFL) in those patients.
Learn More >To analyze the course of symptom-related measures, psychological variables and health-related quality of life (HRQoL) over a 12-month period, and to longitudinally examine symptom-related and psychological factors as predictors for HRQoL in male and female patients with chronic pelvic pain syndrome (CPPS).
Learn More >The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein-protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were down-regulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and suggests that meditation as a behavioral intervention can voluntarily and nonpharmacologically improve the immune response for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.
Learn More >In this study, we investigated the effects of fosphenytoin (fPHT) a water-soluble prodrug of phenytoin, on the pain responses of a mouse herpes zoster (HZ) pain model. Transdermal herpes simplex virus type 1 (HSV-1) inoculation induced mechanical allodynia and hyperalgesia of the hind paw and spontaneous pain-like behaviors, such as licking the affected skin. Intravenous injection of fPHT (15 and 30 mg/kg) alleviated HSV-1-induced provoked pain (allodynia and hyperalgesia). The suppressive effects of fPHT on provoked pain were weaker than those of diclofenac and pregabalin which were used as positive controls. fPHT, diclofenac, and pregabalin significantly suppressed HSV-1-induced spontaneous pain-like behaviors. Among them, high-dose fPHT (30 mg/kg) showed the strongest suppression. Intravenous fPHT may become a viable option for an acute HZ pain, especially for spontaneous pain.
Learn More >Chronic pain is a prevalent medical problem, and its molecular basis remains poorly understood. Here, we demonstrate the significance of the transmembrane protein (Tmem) 160 for nerve injury-induced neuropathic pain. An extensive behavioral assessment suggests a pain modality- and entity-specific phenotype in male Tmem160 global knockout (KO) mice: delayed establishment of tactile hypersensitivity and alterations in self-grooming after nerve injury. In contrast, Tmem160 seems to be dispensable for other nerve injury-induced pain modalities, such as non-evoked and movement-evoked pain, and for other pain entities. Mechanistically, we show that global KO males exhibit dampened neuroimmune signaling and diminished TRPA1-mediated activity in cultured dorsal root ganglia. Neither these changes nor altered pain-related behaviors are observed in global KO female and male peripheral sensory neuron-specific KO mice. Our findings reveal Tmem160 as a sexually dimorphic factor contributing to the establishment, but not maintenance, of discrete nerve injury-induced pain behaviors in male mice.
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