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Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.
Learn More >The definition of chronic migraine has long been debated. Recently, it was suggested to define subjects with at least 8/migraine days as chronic migraine; that is, incorporating so-called high frequency episodic migraine (eight or more migraine days but less than 15 headache days per month).
Learn More >Opioids are commonly used for postoperative pain management in spine surgery. However, few guidelines exist for appropriate prescribing in the acute postoperative phase of care. We identify risk factors for inpatient (IP) opioid use and examine relationships between IP requirements and discharge (DC) opioid prescriptions.
Learn More >Transcutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and spinal cord stimulation (SCS) are used to treat a variety of pain conditions. These non-pharmacological treatments are often thought to work through similar mechanisms, and thus should have similar effects for different types of pain. However, it is unclear if each of these treatments work equally well on each type of pain condition. The purpose of this study was to compared the effects of TENS, MA, and SCS on neuropathic, inflammatory, and non-inflammatory pain models.
Learn More >Chronic pain is a significant public health problem that is associated with several negative health outcomes, including increased health care cost, decreased productivity, and prescription opioid misuse. Although efforts have been made to curb the growing opioid epidemic in the United States, further research is needed to better understand individual difference factors that may be associated with greater pain and opioid misuse. Lower levels of health literacy, defined as the ability to obtain, understand, and use health information to make important decisions regarding health and medical care, has been associated with several chronic illnesses. Yet little work has examined the relationship between health literacy, pain, and opioid misuse among individuals with chronic pain.
Learn More >Fremanezumab, a fully humanized monoclonal antibody targeting calcitonin gene-related peptide, has demonstrated efficacy for the preventive treatment of migraine in adults.
Learn More >Cortical areas including the anterior cingulate cortex (ACC) play critical roles in different types of chronic pain. Most of previous studies focus on the sensory inputs from somatic areas, and less information about plastic changes in the cortex for visceral pain. In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch-clamp recording, behavioral tests, Western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out (AC1 KO) mice. Integrative approaches were used to investigate possible changes of neuronal adenylyl cyclase 1 (AC1) in the ACC after the injury. We found that AC1, a key enzyme for pain-related cortical plasticity, was significantly increased in the ACC in an animal model of irritable bowel syndrome. Inhibiting AC1 activity by a selective AC1 inhibitor NB001 significantly reduced the upregulation of AC1 protein in the ACC. Furthermore, we found that AC1 is required for NMDA GluN2B receptor upregulation and increases of NMDA receptor-mediated currents. These results suggest that AC1 may form a positive regulation in the cortex during chronic visceral pain. Our findings demonstrate that the upregulation of AC1 protein in the cortex may underlie the pathology of chronic visceral pain; and inhibiting AC1 activity may be beneficial for the treatment of visceral pain.
Learn More >This study was to assess the clinical efficacy of epidural injections with tumor necrosis factor-alpha (TNF-α) inhibitor in patients with chronic radicular pain caused by lumbar spinal stenosis (LSS). In a randomized controlled trial (RCT), patients diagnosed with mild-to-moderate LSS underwent epidural intervention with three different drugs and were allocated to TNF-α inhibitor group (Group A), steroid group (Group B) and lidocaine-only group (Group C). All patients were evaluated by visual analog scale (VAS) for leg pain and Oswestry disability index (ODI) to assess function. They all received a 6-month follow-up. Ninety patients were randomly assigned to three groups, for 30 cases in each group. A total of 82 participants (91.1%) completed the follow-up. Pain relief and improvement of movement function after epidural administration in Group A were more significant than those of groups B and C ( < .05) during the 6-month follow-up, while it showed no significant difference between groups B and C ( > .05). Our results indicated that epidural administration with TNF-α inhibitor may be a useful conservative method for the treatment of radicular pain caused by LSS. ClinicalTrials.gov Identifier: NCT04062474.
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