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The pharmacology of Nerve Growth Factor (NGF) and the discovery and development of tanezumab, a monoclonal anti-NGF antibody for the treatment of pain illustrate the complex and unpredictable nature of modern drug development. Initial efforts attempted to use NGF agonistically for Alzheimer's disease and neuropathies. Most unexpectedly, clinical studies unmasked hyperalgesic effects. These observations together with new data emerging from molecular and animal model studies stimulated the idea of using an NGF antagonist for chronic pain. These events also reflect the advances of neuropharmacology from classical small molecule efforts directed at neurotransmitter receptors to modern biotechnology with significant integration in molecular biology, biochemistry, and protein engineering.
Learn More >This study estimated the prevalence of cancer-related pain in working-age cancer survivors (age 25-64 years) and evaluated differences in demographic and clinical variables in those with and without pain. We also investigated the impact of cancer-related pain on health-related quality of life (HRQoL) and employment outcomes in this population.
Learn More >(250 WORDS): Repetitive transcranial magnetic stimulation (rTMS) is a procedure increasingly used to treat patients with central neuropathic pain (CNP), but its efficacy is still under debate.Patients with medically refractory chronic CNP were included in two randomized phases (active/sham), separated by a wash-out period of 8 weeks. Each phase consisted of 4 consecutive rTMS sessions and a final evaluation session, all separated from one another by 3 weeks. High-frequency (20Hz) rTMS was delivered over the primary motor cortex (M1) contralateral to the patient's pain using a neuronavigated robotic system. Patients and clinicians assessing outcomes were blinded to treatment allocation during the trial. The primary outcome measured the percentage of pain relief (%R) from baseline. Secondary outcomes were VAS score, Neuropathic Pain Symptom Inventory (NPSI), analgesic drug consumption and quality of life (EQ-5D).Thirty-six patients performed the entire study with no adverse effects. The analgesic effect for the main criterion (%R) was significantly higher in the active (33.8% CI: [23.88-43.74]) than in the sham phase (13.02% CI:[6.64-19.76]). This was also the case for the secondary outcome VAS (-19.34% CI: [14.31-25.27] vs. -4.83% CI: [1.96-8.18]). No difference was observed for quality of life or analgesic drug consumption. Seventeen patients (47%) were identified as responders but no significant interaction was found between clinical and technical factors considered here and the analgesic response.These results provide strong evidence that 3-weeks spaced high-frequency rTMS of M1 results in a sustained analgesic effect and support the clinical interest of this stimulation paradigm to treat refractory chronic pain.
Learn More >Migraine has been associated with a dysfunctional activation of the trigeminovascular system. Calcitonin gene-related peptide, a neuropeptide released from the trigeminal nerve fibres, has an important role in the pathophysiology of migraine and is a current therapeutic target for migraine treatment.
Learn More >DTB commentaries provide an overview of, and commentary on, a clinical trial, systematic review or observational study.
Learn More >In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown.
Learn More >Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain in general, and members of the non-coding RNA (ncRNA) family, specifically the short, 22 nucleotide microRNAs (miRNAs) and the long non-coding RNAs (lncRNAs) act as master switches orchestrating both immune as well as neuronal processes. Several chronic disorders reveal unique ncRNA expression signatures, which recently generated big hopes for new perspectives for the development of diagnostic applications. lncRNAs may offer perspectives as candidates indicative of neuropathic pain in liquid biopsies. Numerous studies have provided novel mechanistic insight into the role of miRNAs in the molecular sequelae involved in the pathogenesis of neuropathic pain along the entire pain pathway. Specific processes within neurons, immune cells, and glia as the cellular components of the neuropathic pain triad and the communication paths between them are controlled by specific miRNAs. Therefore, nucleotide sequences mimicking or antagonizing miRNA actions can provide novel therapeutic strategies for pain treatment, provided their human homologues serve the same or similar functions. Increasing evidence also sheds light on the function of lncRNAs, which converge so far mainly on purinergic signalling pathways both in neurons and glia, and possibly even other ncRNA species that have not been explored so far.
Learn More >Over the recent years, several small area electrodes have been introduced as tools for preferential stimulation of small cutaneous nerve fibers. However, the performance of the electrodes is highly debated and have not previously been systematically compared. The electrodes have been developed empirically and little is known about the electrical potential they produce in the skin, and how this influences the nerve fiber activation. The objective of the present study was to develop and validate a computational model to compare the preferential stimulation of small fibers for electrodes of different designs.
Learn More >Little is known about the perceptions and attitudes of participants who volunteer in studies involving authorized deception. Thus, this cross-sectional pilot study measured, for the first time, the perceptions about participation in an authorized-deception placebo analgesia study in chronic pain patients with fibromyalgia and assessed whether their perceptions differed from healthy controls.
Learn More >Headaches and pain-related symptoms are the most disabling somatic complaints following mild traumatic brain injury (mTBI). In this study, we reviewed the existing literature examining structural differences in brain morphology and axonal connections, as well as functional differences in brain activity and connectivity associated with pain or post-traumatic headache following mTBI. We searched MEDLINE, EMBASE, PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science databases for: 1) TBI, concussion or post-concussion syndrome, 2) pain or headache, and 3) magnetic resonance imaging, functional MRI or diffusion tensor imaging. Inclusion criteria were original studies written in English on participants with mTBI or concussion diagnosis with results reported on pain and/or headache. Exclusion criteria: Review papers, case studies, documentaries and studies related to moderate to severe TBI. Quality was assessed using Newcastle-Ottawa Scale (NOS) quality assessment tool. Results: Nineteen out of 3439 studies satisfied the inclusion and exclusion criteria. Participants with pain-related symptoms had lower cortical thickness in frontal and parietal cortical areas and spinothalamic tract volume. Differences in axonal connectivity were displayed in the corpus callosum, spinothalamic tract, fornix-septohippocampal circuit, and periaqueductal gray. Less activation in pain-related regions during a heat-pain task-based fMRI was reported in participants with PTH. In conclusion, individuals with pain following mTBI display differences in brain structure and brain function suggesting irregularities in descending pain modulatory system. These findings primarily provide information on neuroimaging differences in adults; there is limited research in pediatric populations.
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