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A better understanding of the multi-dimensional burden and impact of migraine has grown over recent years, yet the tools used to measure these concepts have not been updated to reflect such findings. Additionally, due to the increase in the number of both prophylactic and acute therapeutic options for migraine, a comprehensive assessment of treatment response is necessary. The goal of this project was to develop a patient guided outcome measure which evaluates patient identified efficacy factors when appraising migraine treatment response.
Learn More >This study primarily aimed at investigating the efficacy of analgesia nociception index (ANI) for guiding intraoperative opioid administration in patients receiving surgery under general anesthesia.
Learn More >Calcitonin gene related peptide (CGRP) is a neuropeptide produced by sensory nerves and functions as a pain sensor. It acts by binding to calcitonin like receptor (CLR, protein; Calcrl, gene). CGRP inhibition has been recently introduced as therapeutic treatment of migraine-associated pain. Previous studies have shown that CGRP stimulates bone formation. The aim of our study was to determine whether the inhibition of CGRP signaling negatively impacted fracture healing. Using α-smooth muscle actin (αSMA) Cre animals crossed with Ai9 reporter mice, we showed that CGRP expressing nerves are near αSMA+ cells in the periosteum. In vitro experiments revealed that periosteal cells express Calcrl and Receptor activity modifying protein 1 (Ramp1); and CGRP stimulation increased periosteal cell proliferation. Using a tamoxifen-inducible model αSMACre/CLR we targeted deletion of CLR to periosteal progenitor cells and examined fracture healing. Micro-computed tomography of fractured femurs showed a reduction in bone mass in αSMACre+/CLR female mice relative to controls and callus volume in males. Pharmacological CGRP-CLR inhibition was achieved by subcutaneous delivery of customized pellets with small molecule inhibitor Olcegepant (BIBN-4096) at a dose of 10 μg/day. BIBN-4096-treated C57BL/6J mice had a higher latency toward thermal nociception than placebo treated mice, indicating impaired sensory function through CGRP inhibition. CGRP inhibition also resulted in reduced callus volume, bone mass and bone strength compared to placebo controls. These results indicate that inhibiting CGRP by deleting CLR or by using BIBN-4096, contributes to delayed bone-healing. This article is protected by copyright. All rights reserved.
Learn More >To improve patient safety and pain management, the Centers for Disease Control and Prevention (CDC) released the Guideline for Prescribing Opioids for Chronic Pain (CDC Guideline). Recognizing that issuing a guideline alone is insufficient for transforming practice, CDC supported an Opioid Quality Improvement (QI) Collaborative, consisting of 10 health care systems that represented more than 120 practices across the United States. The research team identified factors related to implementation success using domains described by the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) implementation science framework.
Learn More >Among those with low back pain (LBP), individuals with chronic LBP (CLBP) face different treatment recommendations and incur the majority of suffering and costs. However, the way CLBP has been defined varies greatly. This study used a scoping review and qualitative and quantitative analyses of data from LBP patients to explore this variation. CLBP in most recent randomized controlled trials (RCTs) was defined by duration of pain, most commonly ≥3 months. However, individuals with LBP most often define CLBP by frequency. CLBP has also been defined using a combination of duration and frequency (16% of RCTs and 20% of individuals), including 6% of recent RCTs that followed the NIH Pain Consortium research task force (RTF) definition. Although not a defining characteristic of CLBP for individuals, almost 15% of recent RCTs required CLBP to have a healthcare provider diagnosis. In our LBP sample moving from ≥3 months to the RTF definition reduced the CLBP group size by 25% and resulted in a group that used more pain management options and reported worse health across all outcome measures. A pain duration definition offers ease of application. However, refinements to this definition (e.g., RTF) can identify those who may be better intervention targets. Perspective [max 50 words; now 50]: This article presents the definitions used for chronic low back pain by researchers and individuals, and the impact of these definitions on pain management and health outcomes. This information may help researchers choose better study inclusion criteria and clinicians to better understand their patients' beliefs about chronic low back pain.
Learn More >Pain is a major non-motor symptom that contributes to impaired quality of life in Parkinson's disease (PD). However, the mechanisms and treatment of pain in PD have not been well studied. Dexmedetomidine (Dex) is used for analgesia and sedation during deep brain stimulation (DBS) and may reverse the progression of PD. Here, we explored the effect of Dex on Parkinson's pain and the underlying mechanism. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) to establish a PD model. Then, the mice were treated with Dex (50 µg/kg) or Compound C (CC, 10 mg/kg, AMPK inhibitor). A motor behavioral test was used to validate the PD model, and a plantar test was conducted to assess mechanical and thermal stimulation thresholds. Immunofluorescence and western blotting were used to analyze the level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and the expression of c-Fos, GFAP, p-AMPK, mTOR, NF-κB, TNFα, and IL-6 in the dorsal horn of the spinal cord (DHSC). We found that mice exhibited motor dysfunction and mechanical allodynia and thermal hyperalgesia after MPTP injection, and these changes were partially reversed by Dex. Dex also reduced MPTP-induced astrocyte activation and TNFα and IL-6 expression, increased p-AMPK and reduced mTOR and NF-κB expression in DHSC. Moreover, the effects of Dex were partially reversed by the AMPK inhibitor Compound C. Conclusions: These findings reveal that Dex protects dopaminergic neurons in PD and alleviates pain by reducing the activation of DHSC astrocytes through the AMPK/mTOR/NF-κB pathway. Therefore, Dex may be a potential drug for treating Parkinson's pain.
Learn More >Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents. However, its underlying mechanisms remain incompletely defined. In this study, we demonstrate that green light exposure reduced post-surgical hypersensitivity in rats. Moreover, this therapy potentiated the antinociceptive effects of morphine and ibuprofen on mechanical allodynia in male rats. Importantly, in female rats, GLED potentiated the antinociceptive effects of morphine but did not affect that of ibuprofen. We showed that green light increases endogenous opioid levels while lessening synaptic plasticity and neuroinflammation. Importantly, this study reveals new insights into how light exposure can affect neuroinflammation and plasticity in both genders. Clinical translation of these results could provide patients with improved pain control and decrease opioid consumption. Given the noninvasive nature of green light, this innovative therapy would be readily implementable in hospitals. PERSPECTIVE: This study provides a potential additional therapy to decrease post-surgical pain. Given the safety, availability, and the efficacy of green light therapy, there is a significant potential for advancing the green light therapy to clinical trials and eventual translation to clinical settings.
Learn More >We hypothesized that the addition of coenzyme Q10 (CoQ10) to pregabalin might be helpful in improving symptoms in patients suffering from painful diabetic neuropathy (PDN).
Learn More >TRPA1 and TRPM8 are transient receptor potential channels expressed in trigeminal neurons that are related to pathophysiology in migraine models. Here we use a mouse model of nitroglycerine-induced chronic migraine that displays a sexually dimorphic phenotype, characterized by mechanical hypersensitivity that develops in males and females, and is persistent up to day 20 in female mice, but disappears by day 18 in male mice. TRPA1 is required for development of hypersensitivity in males and females, whereas TRPM8 contributes to the faster recovery from hypersensitivity in males. TRPM8-mediated antinociception effects required the presence of endogenous testosterone in males. Administration of exogenous testosterone to females and orchidectomized males led to recovery from hypersensitivity. Calcium imaging and electrophysiological recordings in in vitro systems confirmed testosterone activity on murine and human TRPM8, independent of androgen receptor expression. Our findings suggest a protective function of TRPM8 in shortening the time frame of hypersensitivity in a mouse model of migraine.
Learn More >At present, there is no objective and absolute measure of nociception, although various monitoring techniques have been developed. One such technique is the Analgesia Nociception Index (ANI), which is calculated from heart rate variability that reflects the relative parasympathetic tone. ANI is expressed on a non-unit scale of 0-100 (100 indicates maximal relative parasympathetic tone). Several studies indicated that ANI-guided anesthesia may help reduce intraoperative opioid use. The usefulness of ANI in the intensive care unit (ICU) and during surgery has also been reported. However, some limitations of ANI have also been reported; for example, ANI is affected by emotions and some drugs. In 2022, a high frequency variability index (HFVI), which was renamed from ANI and uses the same algorithm as ANI, was commercialized; therefore, ANI/HFVI are currently in the spotlight. Unlike ANI, HFVI can be displayed along with other biometric information on the Root monitor. ANI/HFVI monitoring may affect the prognosis of not only patients in the perioperative period but those in ICU, those who receive home medical care, or outpatients. In this article, we present an updated review on ANI that has been published in the last decade, introduce HFVI, and discuss the outlooks of ANI/HFVI.
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