Chronic Morphine Modulates PDGFR-β and PDGF-B Expression and Distribution in Dorsal Root Ganglia and Spinal Cord in Male Rats.

The analgesic effect of opioids decreases over time due to the development of analgesic tolerance. We have shown that inhibition of the platelet-derived growth factor beta (PDGFR-β) signaling eliminates morphine analgesic tolerance in rats. Although the PDGFR-β and its ligand, the platelet-derived growth factor type B (PDGF-B), are expressed in the substantia gelatinosa of the spinal cord (SG) and in the dorsal root ganglia (DRG), their precise distribution within different cell types of these structures is unknown.

Preventing spread of aerosolized infectious particles during medical procedures: A lab-based analysis of an inexpensive plastic enclosure.

Severe viral respiratory diseases, such as SARS-CoV-2, are transmitted through aerosol particles produced by coughing, talking, and breathing. Medical procedures including tracheal intubation, extubation, dental work, and any procedure involving close contact with a patient's airways can increase exposure to infectious aerosol particles. This presents a significant risk for viral exposure of nearby healthcare workers during and following patient care.

Subanalgesic morphine doses augment fentanyl analgesia by interacting with delta opioid receptors in male rats.

Opioids are commonly used for the treatment of postoperative and post-traumatic pain; however, their therapeutic effectiveness is limited by undesirable and life-threatening side effects. Researchers have long attempted to develop opioid co-administration therapies that enhance analgesia, but the complexity of opioid analgesia and our incomplete mechanistic understanding has made this a daunting task. We discovered that subanalgesic morphine doses (100 ng/kg-10 µg/kg) augmented the acute analgesic effect of fentanyl (20 µg/kg) following subcutaneous drug co-administration to male rats.

Use of healthcare resources in patients with low back pain and comorbid depression or anxiety.

Background Context: Psychological comorbidities are important prognostic factors for low back pain (LBP). To develop improved treatment paradigms, it is first necessary to characterize and determine current patterns of treatment in this population.

Purpose: Identify how comorbid depression or anxiety in patients with LBP is related to use of healthcare resources.

Neuropathic pain generates silent synapses in thalamic projection to anterior cingulate cortex.

Pain experience can change the central processing of nociceptive inputs, resulting in persistent allodynia and hyperalgesia. However, the underlying circuit mechanisms remain underexplored. Here, we focus on pain-induced remodeling of the projection from the mediodorsal thalamus (MD) to the anterior cingulate cortex (ACC), a projection that relays spinal nociceptive input for central processing.

EGFR Signaling Causes Morphine Tolerance and Mechanical Sensitization in Rats.

The safety and efficacy of opioids are compromised as analgesic tolerance develops. Opioids are also ineffective against neuropathic pain. Recent reports have suggested that inhibitors of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), may have analgesic effects in cancer patients suffering from neuropathic pain.

An assay for chemical nociception in larvae.

Chemically induced nociception has not yet been studied intensively in genetically tractable models. Hence, our goal was to establish a assay that can be used to study the cellular and molecular/genetic bases of chemically induced nociception. larvae exposed to increasing concentrations of hydrochloric acid (HCl) produced an increasingly intense aversive rolling response.

Growth Factor Signaling Regulates Mechanical Nociception in Flies and Vertebrates.

Mechanical sensitization is one of the most difficult clinical pain problems to treat. However, the molecular and genetic bases of mechanical nociception are unclear. Here we develop a model of mechanical nociception to investigate the ion channels and signaling pathways that regulate mechanical nociception.

Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain.

Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating inflammatory pain. We show that platelet-derived growth factor (PDGF)-BB applied in vitro causes repetitive firing of dissociated nociceptor-like rat dorsal root ganglion neurons and decreased their threshold for action potential generation.

A "tail" of opioid receptor variants.

Opioids are the gold-standard treatment for severe pain. However, potentially life-threatening side effects decrease the safety and effectiveness of these compounds. The addiction liability of these drugs has led to the current epidemic of opioid abuse in the US.

Opioids: keeping the good, eliminating the bad.

Two new studies show that mechanisms mediating the opioid side effects of tolerance, hyperalgesia and physical dependence are mediated spinally and can be dissociated from analgesia. These side effects can be selectively targeted by clinically available drugs without affecting their pain-relieving effects.

Detection and Quantification of Protein Spots by Pinnacle.

Accurate spot detection and quantification is a challenging task that must be performed effectively in order to properly extract the proteomic information from two-dimensional (2-D) gel electrophoresis images. In Morris et al., Bioinformatics 24:529-536, 2008, we introduced Pinnacle, an automatic, fast, effective noncommercial package for spot detection and quantification for 2-D gel images, and subsequently we have developed a freely available gui-based interface for applying the method to a set of gels.

Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.

Unlabelled: Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind.

Platelet-derived growth factor receptor-β antagonism restores morphine analgesic potency against neuropathic pain.

Background: Chronic, intractable pain is a problem of pandemic proportions. Pain caused by nerve injuries (neuropathic pain) is extremely difficult to treat. For centuries, opiates such as morphine have been the first-line treatment for severe chronic pain.

Blockade of PDGFR-β activation eliminates morphine analgesic tolerance.

For centuries, opioid drugs have been the mainstay of chronic pain treatment. However, over time analgesic tolerance develops, leaving few treatment options. Here we show that platelet-derived growth factor receptor-β (PDGFR-β)-mediated signaling plays a key role in morphine tolerance.

Hedgehog signaling regulates nociceptive sensitization.

Background: Nociceptive sensitization is a tissue damage response whereby sensory neurons near damaged tissue enhance their responsiveness to external stimuli. This sensitization manifests as allodynia (aversive withdrawal to previously nonnoxious stimuli) and/or hyperalgesia (exaggerated responsiveness to noxious stimuli). Although some factors mediating nociceptive sensitization are known, inadequacies of current analgesic drugs have prompted a search for additional targets.

AUTOMATED ANALYSIS OF QUANTITATIVE IMAGE DATA USING ISOMORPHIC FUNCTIONAL MIXED MODELS, WITH APPLICATION TO PROTEOMICS DATA.

Image data are increasingly encountered and are of growing importance in many areas of science. Much of these data are quantitative image data, which are characterized by intensities that represent some measurement of interest in the scanned images. The data typically consist of multiple images on the same domain and the goal of the research is to combine the quantitative information across images to make inference about populations or interventions.

Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain.

Objective: Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia.

Results: In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced.

Statistical contributions to proteomic research.

Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results.

Informatics and statistics for analyzing 2-d gel electrophoresis images.

Despite recent progress in "shotgun" peptide separation by integrated liquid chromatography and mass spectrometry (LC/MS), proteome coverage and reproducibility are still limited with this approach and obtaining enough replicate runs for biomarker discovery is a challenge. For these reasons, recent research demonstrates that there is a continuing need for protein separation by two-dimensional gel electrophoresis (2-DE). However, with traditional 2-DE informatics, the digitized images are reduced to symbolic data through spot detection and quantification before proteins are compared for differential expression by spot matching.

Evaluating the performance of new approaches to spot quantification and differential expression in 2-dimensional gel electrophoresis studies.

Spot detection and quantification for 2-DE are challenging and important tasks to fully extract the proteomic information from these data. Traditional analytical methods have significant weaknesses, including spot mismatching and missing data, which require time-consuming manual editing to correct, dramatically decreasing throughput and compromising the objectivity and reproducibility of the analysis. To address this issue, we developed Pinnacle, a novel, quick, automatic, noncommercial method that borrows strength across gels in spot detection and has been shown to yield more precise spot quantifications than traditional methods.

SIMS and MALDI MS imaging of the spinal cord.

The application of MS to imaging, or MS imaging (MSI), allows for the direct investigation of tissue sections to identify biological compounds and determine their spatial distribution. We present an approach to MSI that combines secondary ion MS (SIMS) and MALDI MS for the imaging and analysis of rat spinal cord sections, thereby enhancing the chemical coverage obtained from an MSI experiment. The spinal cord is organized into discrete, anatomically defined areas that include motor and sensory networks composed of chemically diverse cells.

The myth of automated, high-throughput two-dimensional gel analysis.

Many software packages have been developed to process and analyze 2-D gel images. Some programs have been touted as automated, high-throughput solutions. We tested five commercially available programs using 18 replicate gels of a rat brain protein extract.