• Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go
    by Shirin Sadighparvar on 9 Giugno 2023

    Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better...

  • Upper limb and lower limb radiofrequency treatments in orthopaedics
    by E Carlos Rodríguez-Merchán on 8 Giugno 2023

    Radiofrequency (RF) is a minimally invasive technique for disrupting or altering nociceptive pathways to treat musculoskeletal neuropathic and nociplastic pain. RF has been employed to treat painful shoulder, lateral epicondylitis, knee and hip osteoarthritis, chronic knee pain, Perthes disease, greater trochanteric pain syndrome, plantar fasciitis, and painful stump neuromas; it has also been employed before and after painful total knee arthroplasty and after anterior cruciate ligament...

  • Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury
    by Kerri D Pryce on 8 Giugno 2023

    The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. We developed a mouse model of oxycodone exposure and subsequent withdrawal in the presence or absence of chronic neuropathic pain. Oxycodone withdrawal alone triggered robust gene expression adaptations in the nucleus accumbens, medial prefrontal cortex and ventral tegmental area, with numerous genes and pathways selectively affected by oxycodone withdrawal...

  • Atrial fibrillation induced by gabapentin: a case report
    by Sung Hwan Park on 8 Giugno 2023

    CONCLUSION: With rapidly increasing usage of gabapentin for approved and off-label indications, it is important to identify unintended adverse effects of this drug as they are considered safe alternatives to opioids. New-onset atrial fibrillation could be induced by gabapentin in young individuals.

  • Potential sex differences in activation of pain-related brain regions in nonhuman primates with a unilateral spinal nerve ligation
    by Kanae Murata on 7 Giugno 2023

    The lack of truly robust analgesics for chronic pain is owed, in part, to the lack of an animal model that reflects the clinical pain state and of a mechanism-based, objective neurological indicator of pain. The present study examined stimulus-evoked brain activation with functional magnetic resonance imaging in male and female cynomolgus macaques following unilateral L7 spinal nerve ligation and the effects of clinical analgesics pregabalin, duloxetine, and morphine on brain activation in these...

  • Gut microbiota in chronic pain: Novel insights into mechanisms and promising therapeutic strategies
    by Liping Liu on 6 Giugno 2023

    Chronic pain remains one of the world's most persistent and unsolved clinical challenges that severely affect patients' quality of life. Presently, considering that the mechanisms underlying chronic pain are not fully understood, there is a lack of effective drugs and interventions to treat chronic pain in clinical practice. Therefore, exploring the pathogenic mechanism of chronic pain and establishing potential targets are the keys to treating chronic pain. Substantial evidence has indicated...

  • K v 7 Channel Opener Retigabine Reduces Self-Administration of Cocaine but Not Sucrose in Rats
    by Esteban S Urena on 9 Giugno 2023

    The increasing rates of drug misuse highlight the urgency of identifying improved therapeutics for treatment. Most drug-seeking behaviors that can be modeled in rodents utilize the repeated intravenous self-administration (SA) of drugs. Recent studies examining the mesolimbic pathway suggest that K (v) 7/KCNQ channels may contribute in the transition from recreational to chronic drug use. However, to date, all such studies used noncontingent, experimenter-delivered drug model systems, and the...

  • Basolateral Amygdala Corticotrophin Releasing Factor Receptor 2 Interacts with Nonmuscle Myosin II to Destabilize Memory
    by Madalyn Hafenbreidel on 9 Giugno 2023

    Inhibiting the actin motor ATPase nonmuscle myosin II (NMII) with blebbistatin (Blebb) in the basolateral amgydala (BLA) depolymerizes actin, resulting in an immediate, retrieval-independent disruption of methamphetamine (METH)-associated memory. The effect is highly selective, as NMII inhibition has no effect in other relevant brain regions (e.g. dorsal hippocampus [dPHC], nucleus accumbens [NAc]), nor does it interfere with associations for other aversive or appetitive stimuli, including...

  • Combined treatment with Sigma1R and A2AR agonists fails to inhibit cocaine self-administration despite causing strong antagonistic accumbal A2AR-D2R complex interactions: the potential role of astrocytes
    by Dasiel O Borroto-Escuela on 9 Giugno 2023

    Previous studies have indicated that acute treatment with the monoamine stabilizer OSU-6162 (5 mg/kg), which has a high affinity for Sigma1R, significantly increased the density of accumbal shell D2R-Sigma1R and A2AR-D2R heteroreceptor complexes following cocaine self-administration. Ex vivo studies using the A2AR agonist CGS21680 also suggested the existence of enhanced antagonistic accumbal A2AR-D2R allosteric interactions after treatment with OSU-6162 during cocaine self-administration....

  • Acute Cocaine Intoxication: An Approach to Severe Hepatic and Renal Dysfunctions
    by Pedro Fernandes Moura on 8 Giugno 2023

    Cocaine is a highly addictive substance. Its poisoning can lead to potentially fatal multi-organ dysfunction. We report a case of cocaine overdose with severe multi-organ dysfunction. A healthy 51-year-old man was admitted to the emergency room due to behaviour changes and seizure after inhaling crack. Multiple dysfunctions were developed, with emphasis on liver and kidney dysfunction, due to their severity. The patient had marked hepatic cytolysis with a peak on the third day with alanine...

  • Potential neonatal toxicity of new psychoactive substances
    by Ryoichi Fujiwara on 8 Giugno 2023

    Cannabis, cocaine, 3,4-methylenedioxymethamphetamine, and lysergic acid diethylamide are psychoactive substances with a significant increase in consumption during the 21st century due to their popularity in medicinal and recreational use. New psychoactive substances (NPSs) mimic established psychoactive substances. NPSs are known as being natural and safe to consumers; however, they are neither natural nor safe, causing severe adverse reactions, including seizures, nephrotoxicity, and sometimes...

  • An epigenetic synopsis of parental substance use
    by Jamie O Lo on 7 Giugno 2023

    The rate of substance use is rising, especially among reproductive-age individuals. Emerging evidence suggests that paternal pre-conception and maternal prenatal substance use may alter offspring epigenetic regulation (changes to gene expression without modifying DNA) and outcomes later in life, including neurodevelopment and mental health. However, relatively little is known due to the complexities and limitations of existing studies, making causal interpretations challenging. This review...

  • Recovery of clinical, cognitive and cortical activity measures following mild traumatic brain injury (mTBI): A longitudinal investigation
    by Hannah L Coyle on 28 Maggio 2023

    The mechanisms that underpin recovery following mild traumatic brain injury (mTBI) remain poorly understood. Identifying neurophysiological markers and their functional significance is necessary to develop diagnostic and prognostic indicators of recovery. The current study assessed 30 participants in the subacute phase of mTBI (10-31 days post-injury) and 28 demographically matched controls. Participants also completed 3 month (mTBI: N = 21, control: N = 25) and 6 month (mTBI: N = 15, control: N...

  • Transcranial Stimulation for the Treatment of Stimulant Use Disorder
    by Amber N Edinoff on 28 Marzo 2023

    The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. Furthermore, approximately one of every four MIs is cocaine-induced among patients aged 18 to 45. Methamphetamine use has been associated with nerve terminal damage in the dopaminergic system resulting in impaired motor function, cognitive...

  • Sex differences in mild vascular cognitive impairment: A multimodal transcranial magnetic stimulation study
    by Mariagiovanna Cantone on 3 Marzo 2023

    CONCLUSIONS: We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.

  • Disruption of early visual processing in amyloid-positive healthy individuals and mild cognitive impairment
    by Daniel C Javitt on 1 Marzo 2023

    BACKGROUND: Amyloid deposition is a primary predictor of Alzheimer's disease (AD) and related neurodegenerative disorders. Retinal changes involving the structure and function of the ganglion cell layer are increasingly documented in both established and prodromal AD. Visual event-related potentials (vERP) are sensitive to dysfunction in the magno- and parvocellular visual systems, which originate within the retinal ganglion cell layer. The present study evaluates vERP as a function of amyloid...

  • Low-frequency transcranial magnetic stimulation protects cognition in mice with chronic unpredictable mild stress through autophagy regulation
    by Chuan Liu on 28 Febbraio 2023

    Although transcranial magnetic stimulation (TMS) has been approved for the treatment of major depression, few studies have analyzed the ability of low-frequency TMS (LF-TMS) to treat depressive symptoms. Our study confirmed that LF-TMS protects the cognitive function,which can play a certain reference role in the future clinical treatment. The effectiveness of high-frequency TMS therapy has been well documented. However, the use of low-frequency TMS (LF-TMS) in the treatment of depression is...

  • Effective Intracerebral Connectivity in Acute Stroke: A TMS-EEG Study
    by Franca Tecchio on 25 Febbraio 2023

    Stroke is a major cause of disability because of its motor and cognitive sequelae even when the acute phase of stabilization of vital parameters is overcome. The most important improvements occur in the first 8-12 weeks after stroke, indicating that it is crucial to improve our understanding of the dynamics of phenomena occurring in this time window to prospectively target rehabilitation procedures from the earliest stages after the event. Here, we studied the intracortical excitability...

  • Behavioral treatment for migraine prophylaxis in adults: Moderator analysis of a randomized controlled trial
    by Timo Klan on 9 Giugno 2023

    CONCLUSION: Our findings contribute to an individualized treatment selection and suggest that preference for complex behavioral treatment (migraine-specific cognitive-behavioral therapy) should be given to patients with high headache-related disability, increased anxiety, or a comorbid mental disorder.Study Registration: Original study registered in the German Clinical Trials Register (; DRKS-ID: DRKS00011111).

  • Efficacy of IV Valproic Acid and Oral Valproic Acid Tapers for the Treatment of Pediatric Headaches in the Emergency Department
    by Scott Rosenthal on 9 Giugno 2023

    BACKGROUND AND OBJECTIVES: Pediatric headaches, including migraine, are a common reason for emergency department (ED) presentation. IV valproic acid (VPA) followed by oral VPA tapers are often used to abort pediatric headache and reduce recurrence, though limited data exist regarding this approach. This study evaluated the effectiveness of IV VPA and oral VPA tapers for the treatment of acute pediatric headaches in the ED in preventing return encounters.

  • Immune Fitness, Migraine, and Headache Complaints in Individuals with Self-Reported Impaired Wound Healing
    by Jessica Balikji on 9 Giugno 2023

    CONCLUSION: Headaches and migraines are more frequently reported by individuals with self-reported impaired wound healing, and their reported immune fitness is significantly poorer compared to healthy controls. These headache and migraine complaints significantly limit them in their daily activities.

  • Familial Adult Myoclonic Epilepsy: Clinical and Genetic Approach to an Under-recognized Disease
    by Güneş Altıokka Uzun on 8 Giugno 2023

    CONCLUSION: However, as it is not classified as an individual epileptic syndrome by the ILAE, there are still some question marks about this under-recognized disease. The insidious progression of the clinical findings and similarity in phenotypes may lead to misdiagnosis. Clinical and electroclinical international collaborations may help distinguish FAME from other myoclonic epilepsies including juvenile myoclonic epilepsy and slow-progressive forms of progressive myoclonic epilepsy and movement...

  • ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache
    by Erika Liktor-Busa on 8 Giugno 2023

    INTRODUCTION: The high prevalence and severe symptoms of migraines in humans emphasizes the need to identify underlying mechanisms that can be targeted for therapeutic benefit. Clinical Endocannabinoid Deficiency (CED) posits that reduced endocannabinoid tone may contribute to migraine development and other neuropathic pain conditions. While strategies that increase levels of the endocannabinoid n-arachidonoylethanolamide have been tested, few studies have investigated targeting the levels of...

  • Genome-phenome wide association study of broadly defined headache
    by Wan-Ting Hsu on 8 Giugno 2023

    Until recently, most genetic studies of headache have been conducted on participants with European ancestry. We therefore conducted a large-scale genome-wide association study of self-reported headache in individuals of East Asian ancestry (specifically those who were identified as Han Chinese). In this study, 108 855 participants were enrolled, including 12 026 headache cases from the Taiwan Biobank. For broadly defined headache phenotype, we identified a locus on Chromosome 17, with the lead...