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This updated systematic review evaluated the efficacy and safety of opioids compared to placebo for chronic osteoarthritis pain.
Learn More >Duloxetine attenuates paclitaxel-induced peripheral nerve injury by inhibiting p53-related pathways.
Paclitaxel is an antineoplastic drug extracted from the Taxus species, and peripheral neuropathy is a common side effect. Paclitaxel-induced peripheral neuropathy (PIPN) seriously affects patient quality of life. Currently, the mechanism of PIPN is still unknown, and few treatments are recognized clinically. Duloxetine is recommend as the only potential treatment for chemotherapy-induced peripheral neuropathy (CIPN) by the American Society of Clinical Oncology (ASCO). However, this guidance lacks a theoretical basis and experimental evidence. Our study suggested that duloxetine could improve PIPN and provide neuroprotection. We explored the potential mechanisms of duloxetine on PIPN. As a result, duloxetine acts by inhibiting PARP cleavage and p53 activation and regulating the Bcl2 family to reverse paclitaxel(PTX)-induced oxidative stress and apoptosis. Taken together, the present study shows that using duloxetine to attenuate PTX-induced peripheral nerve injury and peripheral pain may lead to new clinical targets for CIPN. SIGNIFICANCE STATEMENT: This study reported duloxetine markedly reduces neuropathic pain evoked by Paclitaxel (PTX), and related to PARP, p53 and the Bcl2 family. Our findings thus not only provide an important guidance to support duloxetine to become the first standard chemotherapy-induced peripheral neuropathy (CIPN) drug, but also will find potential new targets and positive control for new CIPN drug development.
Learn More >Cancer pain is a common symptom experienced by patients, caused either by the disease or its treatment. Morphine remains the most effective and recommended treatment for cancer pain. However, cancer patients still do not receive appropriate management for their pain, and under-treatment is common. Lack of knowledge and negative attitudes towards cancer pain and analgesia among professionals, patients and family caregivers are reported as one of the most common barriers to effective cancer pain management (CPM). To systematically review research on the nature and impact of attitudes and knowledge towards CPM, a systematic literature search of 6 databases (the Cochrane library, MEDLINE, PsycINFO, CINAHL, Web of Science and EMBASE) was undertaken in July 2018. Additionally, hand-searching of Google, Google Scholar and reference lists was conducted. The inclusion criteria were adult (18-65 years of age), studies which included attitudes and knowledge towards CPM, studies written in English, published literature only and cross-sectional design. Included studies were critically appraised by two researchers independently using the Joanna Briggs Institute Analytical Cross Sectional Studies Assessment (JBI-ACSSA). A total of 36 studies met the inclusion criteria. The main finding was that among professionals, patients, caregivers and the public there were similar attitudinal barriers to effective CPM. The most commonly cited barriers were fear of drug addiction, tolerance of medication and side effects of opioids. We also found differences between professional groups (physicians versus nurses) and between different countries based on their potential exposure to palliative care training and services. There are still barriers to effective CPM, which might result in unrelieved cancer pain. Therefore, more educational programmes and training for professionals on CPM are needed. Furthermore, patients, caregivers, and the public need more general awareness and adequate level of knowledge about CPM.
Learn More >To investigate sex effects on pain-related behaviors in the medial meniscal transection (MMT) knee osteoarthritis (OA) model.
Learn More >Chronic pain is known to alter the brain's network dynamics. These dynamics are often demonstrated by identifying alterations in the brain network topology. A common approach used for this purpose is graph theory. To date, little is known on how these potentially altered networks in chronic pain relate to the symptoms reported by these patients. Here, we applied a graph theoretical approach to identify network changes in patients suffering from chronic neck pain, a group that is often neglected in chronic pain research. Participants with chronic traumatic and non-traumatic neck pain were compared to healthy pain-free controls. They showed higher levels of self-reported symptoms of sensitization, higher levels of disability and impaired sensorimotor control. The brain suffering from chronic neck pain furthermore showed altered network properties in the posterior cingulate cortex, amygdala and pallidum compared to the healthy pain-free brain. These regions have been identified as brain hubs (i.e. regions that are responsible for orchestrating communication between other brain regions) and are therefore known to be more vulnerable in brain disorders including chronic pain. We were furthermore able to uncover associations between these altered brain network properties and the symptoms reported by patients. Our findings indicate that chronic neck pain patients reflect brain network alterations and that targeting the brain in patients might be of utmost importance.
Learn More >To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data.
Learn More >Glial cells activated by peripheral nerve injury contribute to the induction and maintenance of neuropathic pain by releasing neuromodulating cytokines and chemokines. We investigated the activation of microglia and astrocytes as well as the cellular distribution of the chemokine CCL2 and its receptor CCR2 in the trigeminal subnucleus caudalis (TSC) ipsilateral and contralateral to infraorbital nerve ligature (IONL). The left infraorbital nerve was ligated under aseptic conditions, and sham controls were operated without nerve ligature. Tactile hypersensitivity was significantly increased bilaterally in vibrissal pads of both sham- and IONL-operated animals from day 1 to 7 and tended to normalize in sham controls surviving for 14 days. Activated microglial cells significantly increased bilaterally in the TSC of both sham- and IONL-operated animals with a marked but gradual increase in the ipsilateral TSC from 1 to 7 days followed by a decrease by day 14. In contrast, robust activation of astrocytes was found bilaterally in the TSC of IONL-operated rats from 3 to 14 days with a transient activation in the ipsilateral TSC of sham-operated animals. Cellular distribution of CCL2 varied with survival time. CCL2 immunofluorescence was detected in neurons within 3 days and in astrocytes at later time points. In contrast, CCR2 was found only in astrocytes at all time points with CCR2 intensity being dominant in the ipsilateral TSC. In summary, our results reveal bilateral activation of microglial cells and astrocytes as well as changes in the cellular distribution of CCL2 and its receptor CCR2 in the TSC during the development and maintenance of orofacial neuropathic pain.
Learn More >In patients with migraine, depression is associated with poorer medical prognosis, decreased quality of life, and increased risk of suicidality and disability; yet, behavioral interventions have rarely been investigated. The current study compared the efficacy of two 1-day (5- to 6-h) interventions for co-occurring migraine and depression: (1) acceptance and commitment therapy plus migraine education (ACT-ED), and (2) support plus migraine education (S-ED). One hundred and thirty-six patients with comorbid depression and migraine were randomized to a treatment. One hundred and three (76%) completed the ACT-ED (N = 56) or S-ED (N = 47) workshop. Primary outcomes were depression diagnosis and symptoms. Secondary outcomes were anxiety symptoms, headache-related disability and general functioning, and quality of life. Assessments were completed at baseline and 3 and 6 months following the workshop. At the 6-month follow-up, on categorical outcomes, a significantly greater number of people in the ACT-ED condition no longer met criteria for a major depressive episode and exhibited a > 50% drop in symptoms on the Hamilton Rating Scale of Depression. Similarly, though, weaker results were found when examining depressive symptoms dimensionally. On secondary outcomes, people in the ACT-ED condition exhibited significantly greater improvements in anxiety, headache-related disability, and quality of social relationships, compared to S-ED, No differences between groups were observed in general functioning. A 1-day (5- to 6-h) ACT workshop can deliver substantial and lasting benefits to depressed migraineurs, over and above those provided by group support and education. This approach is an attractive alternative to weekly psychotherapy. Clinicaltrials.gov # NCT02108678.
Learn More >Opioid-based analgesia is routinely used in clinical practice for the management of pain and alleviation of suffering at the end of life. It is well-known that opioid-based medications can be highly addictive, promoting not only abuse but also life-threatening overdoses. The scope of opioid-related adverse events (AEs) beyond these well-known effects remains poorly described. This exploratory analysis investigates potential AEs from drug-drug interactions between opioid and nonopioid medications (ODIs).
Learn More >Spinal cord dorsal horn srGAP3 increases in the initiation phase of neuropathic pain and decreases in the maintenance phase. However, Rac1 activity which can be reduced by srGAP3, decreased in the initiation phase and increased in the maintenance phase. The increased srGAP3 in the initiation phase promotes new immature dendritic spines instigating neuropathic pain. Decreased srGAP3 in the maintenance phase enhances Rac1 activity facilitating maturation of dendritic spines and the persistence of neuropathic pain. srGAP3 siRNA can ameliorate neuropathic pain only when administrated in the initiation phase. The Rac1 inhibitor can ameliorate neuropathic pain only when administrated in the maintenance phase. Combined targeting of srGAP3 in the initiation phase and Rac1 in the maintenance phase can produce optimal analgesic efficacy.
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