Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential

Abstract: Uncoupling the protein–protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2–CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2.2 and depolarization-evoked Ca2+ influx in rat dorsal root ganglia neurons. In vitro studies demonstrated suppression of excitability of small-to-medium diameter dorsal root ganglion and inhibition of subtypes of voltage-gated Ca2+ channels. Sprague-Dawley rats with tibial nerve injury had profound and long-lasting tactile allodynia and ongoing pain. Immediate administration of R9-CBD3-A6K produced enhanced dopamine release from the nucleus accumbens shell selectively in injured animals, consistent with relief of ongoing pain. R9-CBD3-A6K, when administered repeatedly into the central nervous system ventricles of naive rats, did not result in a positive conditioned place preference demonstrating a lack of abusive liability. Continuous subcutaneous infusion of R9-CBD3-A6K over a 24- to 72-hour period reversed tactile allodynia and ongoing pain, demonstrating a lack of tolerance ov...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Background: Despite the critical role that Emergency Medical Services (EMS) provides in the health care system, racial/ethnic treatment disparities in EMS remain relatively unexamined. Objective: To investigate racial/ethnic treatment disparities in pain assessment and pain medication administration in EMS. Research Design: A retrospective analysis was performed on 25,732 EMS encounters from 2015 to 2017 recorded in the Oregon Emergency Medical Services Information System using multivariate logistic regression models to examine the role of patient race/ethnicity in pain assessment and pain medication administration...
Source: Medical Care - Category: Health Management Tags: Original Articles Source Type: research
Conclusions: We found that perceived stigma in health care settings was a potential barrier to good health. Prior studies have illustrated that negative health outcomes are common for patients who avoid or delay care; thus, the unfortunate conclusion is that even in a diverse, heterogeneous community, stigma persists and may negatively affect well-being. Therefore, eliminating stigma in clinical settings should be a top priority for health care providers and public health professionals seeking to improve health equity.
Source: Medical Care - Category: Health Management Tags: Original Articles Source Type: research
Would having diagnosed anxiety or depression affect chances of getting into medical school if the school finds out an applicant has such problems?
Source: Student Doctor Network - Category: Universities & Medical Training Authors: Tags: Pre-Medical - MD Source Type: forums
Publication date: Available online 12 November 2019Source: Brain, Behavior, and ImmunityAuthor(s): Célia Fourrier, Camille Kropp, Agnès Aubert, Julie Sauvant, Carole Vaysse, Jean-Michel Chardigny, Sophie Layé, Corinne Joffre, Nathalie CastanonAbstractMetabolic syndrome represents a major risk factor for severe comorbidities such as cardiovascular diseases or diabetes. It is also associated with an increased prevalence of emotional and cognitive alterations that in turn aggravate the disease and related outcomes. Identifying therapeutic strategies able to improve those alterations is therefore a major s...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
You're reading 7 Ways to Find Peace of Mind and Inner Calm, originally posted on Pick the Brain | Motivation and Self Improvement. If you're enjoying this, please visit our site for more inspirational articles. All our life, we keep on seeking the peace of mind but it is important to understand that it is not something we can buy or seek. We often get indulged in the process of seeking peace rather than attaining it. Happiness or peace is not something we can grasp, it comes from within. Yes, of course, we can try to meet people we love or buy things we like but peace is not just confined to materialistic pleasure. In...
Source: PickTheBrain | Motivation and Self Improvement - Category: Consumer Health News Authors: Tags: featured happiness meditation calm inner peace self improvement Source Type: blogs
Hello: New to this forum. I am a board certified Pain Medicine MD. I have been seeing patients that are interested in stellate ganglion blocks (cervical sympathetic chain) for PTSD, depression, anxiety, etc. Most of these patients found my practice due to the specificity/complexity of this procedure. Apparently, a '60minutes' CBS piece and a Podcast has sparked interest in this procedure for the aforementioned conditions. I have done my due diligence and cannot find literature... PTSD and Stellate Ganglion Blocks
Source: Student Doctor Network - Category: Universities & Medical Training Authors: Tags: Psychiatry Source Type: forums
Publication date: Available online 27 February 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): J.M. Witkin, R. Cerne, P.G. Davis, K.B. Freeman, J.M. do Carmo, J.K. Rowlett, K.R. Methuku, A. Okun, S.D. Gleason, X. Li, M.J. Krambis, M. Poe, G. Li, J.M. Schkeryantz, R. Jahan, L. Yang, W. Guo, L.K. Golani, W.H. Anderson, J.T. CatlowAbstractClinical evidence indicates that positive allosteric modulators (PAMs) of GABAA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABAA receptor PAMs as analgesics is compromised by the central nervous system side effects of n...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research
Abstract: Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain. Rats receiving green LED light (wavelength 525 nm, 8 h/d) showed significantly increased paw withdrawal la...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Abstract: Trigeminal neuralgia (TN) is a neurological condition that presents as excruciating facial pain. Depression and anxiety are commonly associated with TN; however, anxiety and depression disorders in patients with TN and the effects of the various therapeutic strategies for TN on these disorders are not well studied. To evaluate depression and anxiety in patients with trigeminal neuralgia (TN), identify factors that predict their occurrence and study the effect of the percutaneous trigeminal ganglion radiofrequency thermocoagulation (PRT) procedure for alleviating pain on depression and anxiety. Patients with cla...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
Conclusions: Although previous case series have suggested that SGB offers an effective intervention for PTSD, this study did not demonstrate any appreciable difference between SGB and sham treatment on psychological or pain outcomes. Future studies should examine if differences in treatment methods or patient population could allow individuals with PTSD to benefit from SGB, but current evidence does not support widespread or indiscriminant clinical use of the procedure for PTSD.
Source: Regional Anesthesia and Pain Medicine - Category: Anesthesiology Tags: Chronic and Interventional Pain: Original Articles Source Type: research
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