Browse by Audience
The Oxford Catalogue of Opioids: a systematic synthesis of opioid drug names and their pharmacology.
The growing demand for analgesia, coupled with an increasing need to treat opioid dependence and overdose, has escalated the development of novel opioids. We aimed to quantify the number of opioid drugs developed and to catalogue them based on their pharmacology.
Learn More >This study aimed to explore the effects and possible mechanisms of intravenous lidocaine in postherpetic neuralgia (PHN) rats. Mechanical withdrawal thresholds and thermal withdrawal latencies were measured. Open field test, elevated plus maze test, and tail suspension test were used to assess anxiety- and depressive-like behaviors. Microglia and astrocytes in spinal dorsal horn (SDH), prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampus were analyzed. The expression of TNF-α, IL-1β, and IL-4 in SDH and serum were evaluated. Intravenous lidocaine alleviated mechanical allodynia and thermal hypoalgesia, downregulated the expression of TNF-α and IL-1β, and inhibited the activation of microglia and astrocytes in SDH. In addition, it reduced the activation of astrocyte but not microglia in PFC, ACC, and hippocampus. Intravenous lidocaine may relieve PHN by inhibiting the activation of microglia and astrocyte in SDH or by reducing the neuroinflammation and astrocyte activation in PFC, ACC, and hippocampus.
Learn More >Mas gene-related G protein-coupled receptors (MRGPRs) are a GPCR family responsive to various exogenous and endogenous agonists, playing a fundamental role in pain and itch sensation. The primate-specific family member MRGPRX2 and its murine orthologue MRGPRB2 are expressed by mast cells, mediating IgE-independent signaling and pseudo-allergic drug reactions.
Learn More >Paclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored.
Learn More >Over the last six decades (earliest included publication from 1959), clinical trials of migraine preventive treatments have led to the regulatory approval of many medications and devices. Despite similar clinical goals, the outcomes and endpoints used in these trials are broad and not well standardized.
Learn More >Symptoms that resemble allergic reactions, such as pruritus, flushing, and hypotension, are common side effects of therapeutic drugs. In a true allergic reaction, Immunoglobulin E (IgE) antibodies recognize the drug and trigger mediator release from mast cells through cross-linking of IgE receptors. However, many drugs can bypass this pathway and can activate mast cells directly through MRGPRX2, a G protein-coupled receptor that responds to a wide range of small molecules, peptides, and proteins that have little in common except for a net positive charge. This review will provide an overview of MRGPRX2, including its expression pattern, studies of its pharmacology, and its orthologs. It also will review evidence for MRGPRX2 activation by many drugs closely associated with these reactions.
Learn More >First-line pharmacotherapy for neuropathic pain entails the use of systemic antidepressants and anticonvulsants. These drugs are not optimally effective and poorly tolerated, especially for older patients with comorbid conditions. Given the high number of such patients, there is a need for a greater repertoire of safer and more effective analgesics. Clonidine and pentoxifylline are vasodilator agents that work synergistically to enhance tissue perfusion and oxygenation. The topical administration of these drugs, individually and in combination, has shown anti-nociceptive properties in rodent models of neuropathic pain. A topically-administered combination of clonidine and pentoxifylline also effectively reduced the intensity of both spontaneous and evoked pain in healthy volunteers with experimentally-induced neuropathic pain. The next step in advancing this formulation to clinical use is the undertaking of a phase II clinical study to assess its efficacy and safety in neuropathic pain patients.
Learn More >Erenumab is a monoclonal antibody against calcitonin gene-related peptide receptors, which showed efficacy in migraine attack prevention. The aims of the present pilot study were to i) evaluate the effect of single dose of Erenumab 70 mg on laser evoked potentials from trigeminal and brachial stimulation in a cohort of migraine patients; ii) correlate the neurophysiological changes with clinical outcome after 3 months' treatment.
Learn More >Prescription opioids are powerful pain-controlling medications that have both benefits and potentially serious risks. Morphine is one of the preferred analgesics that are widely used to treat chronic pain. However, chronic morphine exposure has been found to cause both functional and structural changes in several brain regions, including the medial prefrontal cortex (mPFC), ventral tegmental area (VTA), and hippocampus (HPC), which lead to addictive behavior. Caveolin-1 (Cav-1), a scaffolding protein of membrane lipid rafts (MLRs), has been shown to organize GPCRs and multiple synaptic signaling proteins within the MLRs to regulate synaptic signaling and neuroplasticity. Previously, we showed that in vitro morphine treatment significantly elevates Cav-1 expression and causes neuroplasticity changes. In this study, we confirmed that chronic morphine exposure can significantly increase Cav-1 expression (P < 0.05) and microtubule-associated protein (MAP-2)-positive neuronal dendritic growth in the hippocampus. Moreover, the rewarding effect and dendritic growth in the HPC induced by chronic morphine exposure were significantly inhibited by hippocampal Cav-1 knockdown. Together, these data suggest that Cav-1 in the hippocampus plays an essential role in the neuroplasticity changes that underlie morphine addiction behaviors.
Learn More >Metabolically Stable Neurotensin Analogs Exert Potent and Long-Acting Analgesia Without Hypothermia.
The endogenous tridecapeptide neurotensin (NT) has emerged as an important inhibitory modulator of pain transmission, exerting its analgesic action through the activation of the G protein-coupled receptors, NTS1 and NTS2. Whereas both NT receptors mediate the analgesic effects of NT, NTS1 activation also produces hypotension and hypothermia, which may represent obstacles for the development of new pain medications. In the present study, we implemented various chemical strategies to improve the metabolic stability of the biologically active fragment NT(8-13) and assessed their NTS1/NTS2 relative binding affinities. We then determined their ability to reduce the nociceptive behaviors in acute, tonic, and chronic pain models and to modulate blood pressure and body temperature. To this end, we synthesized a series of NT(8-13) analogs carrying a reduced amide bond at Lys-Lys and harboring site-selective modifications with unnatural amino acids, such as silaproline (Sip) and trimethylsilylalanine (TMSAla). Incorporation of Sip and TMSAla respectively in positions 10 and 13 of NT(8-13) combined with the Lys-Lys reduced amine bond (JMV5296) greatly prolonged the plasma half-life time over 20 hours. These modifications also led to a 25-fold peptide selectivity toward NTS2. More importantly, central delivery of JMV5296 was able to induce a strong antinociceptive effect in acute (tail-flick), tonic (formalin), and chronic inflammatory (CFA) pain models without inducing hypothermia. Altogether, these results demonstrate that the chemically-modified NT(8-13) analog JMV5296 exhibits a better therapeutic profile and may thus represent a promising avenue to guide the development of new stable NT agonists and improve pain management.
Learn More >