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Current treatment options for chronic pain and depression are largely medication-based, which may cause adverse side effects. Integrative Medical Group Visits (IMGV) combines mindfulness techniques, evidence based integrative medicine, and medical group visits, and is a promising adjunct to medications, especially for diverse underserved patients who have limited access to non-pharmacological therapies.
Learn More >The opioid epidemic is a significant public health crisis, and this problem is particularly prevalent among individuals with chronic pain. Accordingly, there is an urgent need for interventions to mitigate the risk for opioid misuse and opioid use disorder among people with pain. Given that mental health problems, specifically anxiety, are common among people who misuse opioids, it is important to examine factors that link mental health problems with opioid misuse to ultimately inform the development of novel interventions. Anxiety sensitivity, a transdiagnostic vulnerability factor defined as the fear of anxiety-related physical sensations, may be one important mechanism in elevated opioid misuse among persons with chronic pain.
Learn More >A number of studies have been published proposing various approaches to the treatment of neuropathic pain; however, to our knowledge, no attempts have been made to compare gabapentin and fentanyl in patients with lumbar radiculopathy. We evaluated the relative efficacy and safety of fentanyl matrix and gabapentin for the treatment of chronic neuropathic pain of radicular origin. The study was designed as a randomized blind multicentered parallel-group noninferiority trial. A total of 108 patients with moderate-to-severe pain (≥4 intensity on an 11-point numeric rating scale) were randomly prescribed either fentanyl matrix or gabapentin over a period of 56 days. In the primary analysis, the noninferiority of fentanyl matrix treatment was evaluated in relation to the efficacy of gabapentin based on the pain intensity difference (PID) at 56 days after the first dose of the drugs. Secondary endpoints included pain relief, improvement in functional status (the Korean-Oswestry Disability Index (K-ODI)), improvement in depressive symptoms (Korean-Beck Depression Index (K-BDI)) between the 28th and 56th day, and adverse events (AEs). Analysis of the primary efficacy endpoint established the noninferiority of fentanyl matrix compared with gabapentin, with no statistically significant difference observed in the PID after 56 days for the two treatment groups. Similarly, analysis of pain relief revealed no significant differences between the groups on days 28 and 56. There was no difference in the K-ODI and K-BDI between the groups during the study period. The overall incidence of at least one AE was similar for fentanyl matrix (67.3%) and gabapentin (69.6%). The most commonly reported AEs for patients treated with fentanyl matrix and gabapentin included dizziness (30.8% vs. 44.6%, respectively), somnolence (26.9% vs. 35.7%), and constipation (15.4% vs. 17.9%). This study demonstrated that the analgesic effect of fentanyl matrix is noninferior in comparison with gabapentin and supports the use of fentanyl matrix as an effective and safe treatment for moderate-to-severe chronic neuropathic pain. This trial is registered with NCT01127100.
Learn More >: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. : Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group ( = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group ( = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS ( = 12) and sham ts-DCS ( = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. : Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. : Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. www.ClinicalTrials.gov, identifier #NCT02331654.
Learn More >General practitioners' (GPs) views about deprescribing prescription opioid analgesics (POAs) may influence the care provided for patients experiencing chronic noncancer pain (CNCP). There are limited data addressing GPs' beliefs about deprescribing, including their decisions to deprescribe different types of POAs.
Learn More >The experience of chronic non-cancer pain (CNCP) is one of the most common reasons individuals seek medical attention. Patients with CNCP frequently experience concomitant sleep-related problems.
Learn More >The importance of improved physical function as a primary outcome in the treatment of chronic pain is widely accepted. There have been limited attempts to assess the effects mindfulness skills training (MST) has on objective outcomes in chronic pain care.
Learn More >Type-A γ-aminobutyric (GABA) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABA receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (γ-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes and mechanistic effects of these ligands, the closed and desensitized states of the GABA receptor gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding region and the transmembrane, pore-forming region. This work provides a structural framework in which to integrate previous physiology and pharmacology research and a rational basis for the development of GABA receptor modulators.
Learn More >Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis. This narrative review highlights earlier and more recent in vitro, in vivo and human retrospective studies that yield conflicting results as to their immune modulatory effects of morphine on tumor biology. The article examines and explains the discrepancies with regards to the seemingly opposite results of morphine in the tumor milieu. The results of both, earlier studies that demonstrated procarcinogenic effects versus the data of more recent refined rodent studies that more adequately reflect de novo metastasis that yielded neutral or even anti-carcinogenic effects are presented here. Until the results of prospective randomized controlled trials are available to clarify this important question, it is currently not warranted to support opiophobia and opioids continue to constitute a pivotal role in the pain management of cancer patients.
Learn More >Neurotrophins (NTs), particularly Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF), have attracted increasing attention in the context of visceral function for some years. Here, we examined current literature and produced a thorough review on the subject. After initial studies linking NGF to cystitis, it is now well-established that this neurotrophin (NT) is a key modulator of bladder pathologies, including Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS. NGF is upregulated in bladder tissue and its blockade results in major improvements on urodynamic parameters and pain. Further studies expanded showed that NGF is also an intervenient in other visceral dysfunctions such as endometriosis and Irritable Bowel Syndrome (IBS). More recently, BDNF was also shown to play an important role in the same visceral dysfunctions, suggesting that both NTs are determinant factors in visceral pathophysiological mechanisms. While manipulation of NGF and BDNF improves visceral function and reduce pain, suggesting that clinical modulation of these NTs may be important, much is still to be investigated before this step is taken. Another active area of research is centred on urinary NGF and BDNF. Several studies show that both NTs can be found in the urine of patients with visceral dysfunction in much higher concentration than in healthy individuals, suggesting they could be used as potential biomarkers. However, there are still technical difficulties to be overcome, including the lack of a large multicentre placebo controlled studies to prove the relevance of urinary NTs as clinical biomarkers.
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