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Although much is known about the correlates of heroin overdose, less is known about pharmaceutical opioid (PO) overdose. This study aimed to examine correlates of opioid overdose deaths by opioid and compare correlates between opioids.
Learn More >Chronic musculoskeletal pain in adolescence is a significant public health concern with 3-5% of adolescents suffering from significant pain-related disability. Pain-related fear and avoidance of activities has been found to have a significant influence on pain outcomes in children and adolescents and is a risk factor for less favorable response to treatment. To address this need, we developed graded exposure treatment for youth with chronic pain (GET Living). We describe the rationale, design, and implementation of a two-group randomized controlled trial (RCT) enhanced with single-case experimental design (SCED) methodology with a sample of 74 adolescents with chronic musculosketal pain and their parent caregivers. GET Living includes education, behavioral exposures, and parent intervention jointly delivered by pain psychology and physical therapy providers. The multidisciplinary pain management control group includes pain psychology delivered education and pain self-management skills training (e.g., relaxation, cognitive skills) and separate physical therapy. Assessments include brief daily diaries (baseline to discharge, 7-days at 3-month and 6-month follow-up), comprehensive in-person evaluations at baseline and discharge, and questionnaire across all time points (baseline, discharge, 3-month and 6-month follow-up). Primary outcome is pain-related fear avoidance. Secondary outcome is functional disability. We also outline all additional outcomes, exploratory outcomes, covariates, and implementation measures. The objective is to offer a mechanism-based, targeted intervention to youth with musculoskeletal pain to enhance likelihood of return to function.
Learn More >Chronic low back pain has both substantial social and economic impacts on patients and healthcare budgets. Adding to the magnitude of the problem is the difficulty in identifying the exact causes of disc degeneration with modern day diagnostic and imaging techniques. With that said, current non-operative and surgical treatment modalities for discogenic low back pain fails to meet the expectations in many patients and hence the challenge. The objective for newly emerging stem cell regenerative therapy is to treat degenerative disc disease (DDD) by restoring the disc's cellularity and modulating the inflammatory response. Appropriate patient selection is crucial for the success of stem cell therapy. Regenerative modalities for discogenic pain currently focus on the use of either primary cells harvested from the intervertebral discs or stem cells from other sources whether autogenic or allogenic. The microenvironment in which stem cells are being cultured has been recognized to play a crucial role in directing or maintaining the production of the desired phenotypes and may enhance their regenerative potential. This has led to a more specific focus on innovating more effective culturing techniques, delivery vehicles and scaffolds for stem cell application. Although stem cell therapy might offer an attractive alternative treatment option, more clinical studies are still needed to establish on the safety and feasibility of such therapy. In this literature review, we aim to present the most recent and studies related to the use of stem cell therapy in the treatment of discogenic low back pain.
Learn More >To assess the prevalence and characteristics of chronic neck pain, chronic low back pain, and migraine or frequent headaches among Spanish adults in 2014 according to gender, to identify predictors for each of these types of pains, and to compare the prevalence with those found in 2009.
Learn More >To review and discuss the putative role of light, sleep, and the biological clock in cluster headache.
Learn More >Acute and persistent post-traumatic headache are often debilitating consequences of traumatic brain injury. Underlying physiological mechanisms of post-traumatic headache and its persistence remain unknown, and there are currently no approved therapies for these conditions. Post-traumatic headache often presents with a migraine-like phenotype. As calcitonin-gene related peptide promotes migraine headache, we explored the efficacy and timing of intervention with an anti- calcitonin-gene related peptide monoclonal antibody in novel preclinical models of acute post-traumatic headache and persistent post-traumatic headache following a mild traumatic brain injury event in mice.
Learn More >Persistent pain is associated with negative affect originating from hypersensitivity and/or allodynia. The spinal cord is a key area for nociception as well as chronic pain processing. Specifically, the dorsal horn neurons in lamina II (substantia gelatinosa: SG) receive nociceptive inputs from primary afferents such as C fibers and/or Aδ fibers. Transient receptor potential vanilloid 1 (TRPV1) is a major receptor to sense heat as well as nociception. TRPV1 are expressed in the periphery and the central axon terminals of C fibers and/or Aδ fibers in the spinal cord. Activating TRPV1 enhances the release of glutamate in the spinal cord from naïve rodents. Here, we studied whether or not chronic pain could alter the response of TRPV1 channels to exogenous, capsaicin through study of synaptic transmission and neural activity in rat SG neurons. Using in vitro whole-cell patch-clamp recording, we found that bath application of capsaicin facilitated both the frequency and amplitude of miniature and spontaneous excitatory postsynaptic currents beyond a nerve injury and a complete Freund's adjuvant injection observed in the naïve group. Strikingly, capsaicin produced larger amplitudes of inward currents in pain models than compared to the naïve group. By contrast, the proportions of neurons that show capsaicin-induced inward currents were similar among naïve and pain groups. Importantly, the capsaicin-induced inward currents were conducted by TRPV1 and required calcium influx that was independent of voltage-gated calcium channels. Our study provides fundamental evidence that chronic inflammation and neuropathic pain models amplify the release of glutamate through the activation of TRPV1 in central axon terminals, and that facilitation of TRPV1 function in rat spinal SG neurons may contribute to enhanced capsaicin-induced inward currents.
Learn More >Endogenous opioid peptides and exogenous opioids modulate immune function and animal and human studies have shown that some have a depressant immunomodulatory effect. This is potentially of high clinical significance for example in cancer patients and surgery.The primary objective of this pilot study was to evaluate the effect of morphine and oxycodone on immune pathways associated with immunosuppression in gynecological laparotomy patients.Gene expression was analyzed in CD4+, CD8+ and NK cells using the 3' Affymetrix microarray. Patients were randomized to receive morphine, oxycodone, or non-opioid 'control' analgesia during and after surgery. Genes demonstrating differential expression were those with a ≥±2-fold difference and p-value≤0.05 following ANOVA. Cytometric bead array and NK cell degranulation assay were used to investigate changes in serum cytokine concentration and in NK cell cytotoxicity, respectively. Forty patients had satisfactory RNA which was hybridized to gene chips. Genes were identified (Partek® Genomics Suite® 6.6) at baseline, 2 h, 6 h and 24 h and were either ≥2-fold up or down-regulated from baseline.At 2 h, a large number of genes were down-regulated with morphine but not with control analgesia or oxycodone. Statistically significant increases in IL-6 concentrations were induced by morphine only; NK cell activity was suppressed with morphine, but maintained with oxycodone and epidural analgesia.Gene expression profiles suggest that at 2 h post-incision morphine appeared to be immunosuppressive as compared to oxycodone and non-opioid control analgesia.
Learn More >Opioid use for chronic pain is limited by severe central adverse effects. We examined whether activating mu-opioid receptors (MORs) in the peripheral nervous system attenuates spinal cord injury (SCI) pain-like behavior in mice. We produced a contusive SCI at the T10 vertebral level and examined motor and sensory dysfunction for 6 weeks. At 6 weeks, we tested the effect of subcutaneous (s.c.) injection of dermorphin [D-Arg2, Lys4] (1-4) amide (DALDA), a peripherally acting MOR-preferring agonist, on mechanical and heat hypersensitivity. Basso mouse scale score was significantly decreased after SCI, and mice showed hypersensitivity to mechanical and heat stimulation at the hind paw beginning at 2 weeks, as indicated by increased paw withdrawal frequency to mechanical stimulation and decreased paw withdrawal latency to heat stimulation. In wild-type SCI mice, DALDA (1 mg/kg, s.c.) attenuated heat but not mechanical hypersensitivity. The effect was blocked by pretreatment with an intraperitoneal injection of methylnaltrexone (5 mg/kg), a peripherally restricted opioid receptor antagonist, and was also diminished in Pirt-MOR conditional knockout mice. DALDA did not adversely affect exploratory activity or induced preference to drug treatment in SCI mice. In vivo calcium imaging showed that DALDA (1, 10 mg/kg, s.c.) inhibited responses of small DRG neurons to noxious heat stimulation in Pirt-GCaMP6s mice after SCI. Western blot analysis showed upregulation of MOR in the lumbar spinal cord and sciatic nerves at 6 weeks post-SCI. Our findings suggest that peripherally acting MOR agonist may inhibit heat hypersensitivity below the injury level with minimal adverse effects.
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