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In this report we describe a series of patients with a previously undescribed headache.
Learn More >The phase III research evaluating migraine prophylaxis therapy (PREEMPT) protocol was developed in low-risk migraine patients. We studied longitudinal response to treatment in a sequential retrospective observational cohort to evaluate predictors of effectiveness in patients with multiple overlapping pain syndromes treated in a quaternary pain management clinic.
Learn More >The aim of this study was to explore the effects of mindfulness-based stress reduction (MBSR) on reducing the psychological and physical symptoms in patients with postherpetic neuralgia (PHN). A total of 50 patients with PHN from January 2017 to September 2018 were selected into the intervention group and the control group. Both groups received routine care, whereas the intervention group also was given an 8-week of MBSR. Psychological (depression and anxiety) and physical (pain) symptoms were assessed before and after the intervention. The study demonstrated evidence of MBSR effectiveness in reducing depression (p < 0.01), anxiety (p < 0.01), and pain (p < 0.01) scores after intervention for herpetic patients with neuralgia. MBSR can effectively alleviate depression, anxiety, and pain in patients with PHN. Our results provide clinical effectiveness evidence that MBSR works to improve the psychological and physical symptoms with the greatest improvement occurring during the 8-week program.
Learn More >More than 15,000 children die annually in the United States due to an underlying life-limiting disease and the majority of those children experience distressing symptoms, which are not adequately relieved, such as pain and dyspnea. Multimodal analgesia, that is multiple agents, interventions, rehabilitation, psychological modalities, and integrative (nonpharmacologic) therapies, act synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality. However, opioids, such as morphine, fentanyl, hydromorphone, oxycodone, and methadone (in the United Kingdom: diamorphine) remain the mainstay medication to effectively treat pain and dyspnea in children with serious illness.
Learn More >To examine the longitudinal course of vasomotor symptoms (VMS) in women with a history of migraine, in comparison to women without a history of migraine disease.
Learn More >Non-selective glutamate AMPA receptor antagonists are efficacious in chronic pain, but have significant tolerability issues, likely arising from the ubiquitous expression of AMPA receptors in CNS. Recently, LY3130481 has been shown to selectively block AMPA receptors co-assembled with the auxiliary protein, TARP γ8, which is highly expressed in hippocampus, but also in pain pathways, including anterior cingulate (ACC) and somatosensory (SS) cortices and spinal cord, suggesting that selective blockade γ8/AMPA receptors may suppress nociceptive signaling with fewer CNS side effects. The potency of LY3130481 on recombinant γ8-containing AMPA receptors was modulated by co-expression with other TARPs; γ2 subunits affected activity more than γ3 subunits. Consistent with these findings, LY3130481 had decreasing potency on receptors from rat hippocampal, cortical, spinal cord, and cerebellar neurons that was replicated in tissue from human brain. LY3130481 partially suppressed, whereas the non-selective AMPA antagonist GYKI53784 completely blocked AMPA receptor-dependent EPSPs in ACC and spinal neurons in vitro. Similarly, LY3130481 attenuated short-term synaptic plasticity in spinal sensory neurons in vivo in response stimulation of peripheral afferents. LY3130481 also significantly reduced nocifensive behaviors after intraplantar formalin that was correlated with occupancy of CNS γ8-containing AMPA receptors. In addition, LY3130481 dose-dependently attenuated established gait impairment after joint damage and tactile allodynia after spinal nerve ligation; all in the absence of motor side effects. Collectively, these data demonstrate that LY3130481 can suppress excitatory synaptic transmission and plasticity in pain pathways containing γ8/AMPA receptors and significantly reduce nocifensive behaviors, suggesting a novel, effective and safer therapy for chronic pain conditions.
Learn More >To understand the process of change at an individual level, this study used a single-case experimental design to evaluate how change in potential mediators related to change in disability over time, during an exposure-based behavioural intervention in four people with chronic low back pain and high pain-related fear. A second aim was to evaluate whether the change (sequential or simultaneous) in mediators and disability occurred at the same timepoint for all individuals.
Learn More >Transmembrane member 16A (TMEM16A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contraction, and may be important in peripheral pain transmission. To explore the role of TMEM16A in the persistent hyperalgesia that results from chronic constriction injury-induced neuropathic pain, a rat model of the condition was established by ligating the left sciatic nerve. A TMEM16A selective antagonist (10 μg T16Ainh-A01) was intrathecally injected at L5-6. For measurement of thermal hyperalgesia, the drug was administered once at 14 days and thermal withdrawal latency was recorded with an analgesia meter. For measurement of other indexes, the drug was administered at 12 days, once every 6 hours, totally five times. The measurements were performed at 14 days. Western blot assay was conducted to analyze TMEM16A expression in the L4-6 dorsal root ganglion. Immunofluorescence staining was used to detect the immunoreactivity of TMEM16A in the L4-6 dorsal root ganglion on the injured side. Patch clamp was used to detect electrophysiological changes in the neurons in the L4-6 dorsal root ganglion. Our results demonstrated that thermal withdrawal latency was shortened in the model rats compared with control rats. Additionally, TMEM16A expression and the number of TMEM16A positive cells in the L4-6 dorsal root ganglion were higher in the model rats, which induced excitation of the neurons in the L4-6 dorsal root ganglion. These findings were inhibited by T16Ainh-A01 and confirm that TMEM16A plays a key role in persistent chronic constriction injury-induced hyperalgesia. Thus, inhibiting TMEM16A might be a novel pharmacological intervention for neuropathic pain. All experimental protocols were approved by the Animal Ethics Committee at the First Affiliated Hospital of Shihezi University School of Medicine, China (approval No. A2017-170-01) on February 27, 2017.
Learn More >The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (Nav) 1.7. Still, recent studies targeting Nav1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells (iPS cells) from IEM patients with the Nav1.7/I848T mutation into sensory nociceptors. Action potentials in these IEM nociceptors displayed a decreased firing threshold, an enhanced upstroke and afterhyperpolarization, all of which may explain the increased pain experienced by patients. Subsequently, we investigated the voltage dependence of the tetrodotoxin-sensitive Nav activation in these human sensory neurons using a specific pre-pulse voltage protocol. The IEM mutation induced a hyperpolarizing shift of Nav activation which leads to activation of Nav1.7 at more negative potentials. Our results indicate that Nav1.7 is not active during subthreshold depolarizations, but that its activity defines the action potential threshold and contributes significantly to the action potential upstroke. Thus, our model system with iPS cell-derived sensory neurons provides a new rationale for Nav1.7 function and promises to be valuable as a translational tool to profile and develop more efficacious clinical analgesics.
Learn More >No consensus exists for defining chronic preoperative opioid use. Most spine studies rely solely on opioid duration to stratify patients into preoperative risk categories.
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