J Venom Anim Toxins Incl Trop Dis
November 2024
Background: Medications currently used to treat pain are frequently associated with serious adverse effects and rapid development of tolerance. Thus, there is a need to develop more effective, and safer medicines for the population. Blocking NMDA receptors (NMDAR) has shown to be a promising target for the development of new drugs.
View Article and Find Full Text PDFCancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored.
View Article and Find Full Text PDFPain Rep
February 2023
Introduction: Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon in which exposure to opioids can increase sensitivity to painful stimuli. Currently, several drugs have been used in an attempt to prevent OIH. We design this study to address the effect of preemptive treatment with ketamine, lidocaine, and ascorbic acid in a rat preclinical model of perioperative opioid-induced hyperalgesia.
View Article and Find Full Text PDFCell-specific alternative splicing of pre-mRNA generates functionally distinct voltage-gated Ca2.2 channels. Ca2.
View Article and Find Full Text PDFVoltage-gated calcium channels (VGCCs) are targeted to treat pain conditions. Since the discovery of their relation to pain processing control, they are investigated to find new strategies for better pain control. This review provides an overview of naturally based and synthetic VGCC blockers, highlighting new evidence on the development of drugs focusing on the VGCC subtypes as well as mixed targets with pre-clinical and clinical analgesic effects.
View Article and Find Full Text PDFIon channels play critical roles in generating and propagating action potentials and in neurotransmitter release at a subset of excitatory and inhibitory synapses. Dysfunction of these channels has been linked to various health conditions, such as neurodegenerative diseases and chronic pain. Neurodegeneration is one of the underlying causes of a range of neurological pathologies, such as Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, brain injury, and retinal ischemia.
View Article and Find Full Text PDFSome people living with HIV present painful sensory neuropathy (HIV-SN) that is pharmacoresistant, sex-associated, and a major source of morbidity. Since the specific mechanisms underlying HIV-SN are not well understood, the aim of our study was to characterize a novel model of painful HIV-SN by combining the HIV-1 gp120 protein and the antiretroviral stavudine (d4T) in mice and to investigate the pronociceptive role of the family 2 voltage-gated calcium channel (VGCC) α1 subunit (Cav2.X channels) in such a model.
View Article and Find Full Text PDFCalcium (Ca ) is an important second messenger in charge of many critical processes in the central nervous system (CNS), including membrane excitability, neurotransmission, learning, memory, cell proliferation, and apoptosis. In this way, the voltage-gated calcium channels (VGCCs) act as a key supply for Ca entry into the cytoplasm and organelles. Importantly, the dysregulation of these channels has been reported in many neurological diseases of young-onset, with associated genetic factors, such as migraine, multiple sclerosis, and Huntington's disease.
View Article and Find Full Text PDFMol Neurobiol
July 2022
CTK 01512-2 toxin is a recombinant peptide of the Phα1β version derived from the venom of the Phoneutria nigriventer spider. It acts as an N-type voltage-gated calcium channel (VGCC) blocker and shows a prolonged effect on preventing and reducing nociception. Herein, CTK 01512-2 was tested on two models of persistent pain, the chronic post-ischemia pain (CPIP) and the paclitaxel-induced peripheral neuropathy, to evaluate its systemic, intrathecal, and intracerebroventricular effects on mechanical hypersensitivity and thermal allodynia.
View Article and Find Full Text PDFNew Findings: What is the central question of this study? We investigated the effects of intrathecal administration of a novel toxin, CTK 01512-2, in a mouse model of Huntington's disease. We asked whether spinal cord neurons can represent a therapeutic target, given that the spinal cord seems to be involved in motor symptoms of Huntington's disease. Pharmacological approaches focusing on the spinal cord and skeletal muscles might represent a more feasible strategy than a high-risk brain intervention.
View Article and Find Full Text PDFPreclinical evidence suggests the potential of Ph1, a toxin obtained from the venom of spider , as a new analgesic drug. Molecular brain imaging techniques have afforded exciting opportunities to examine brain processes in clinical pain conditions. This paper aims to study the brain regions involved in the analgesic effects of Ph1 compared with Morphine, in a model of acute pain induced by formalin in Sprague Dawley rats.
View Article and Find Full Text PDFPhα1β is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice.
View Article and Find Full Text PDFJ Venom Anim Toxins Incl Trop Dis
August 2021
Background: venom contains Phα1β. This toxin and its recombinant form have a remarkable analgesic potential that is associated with blockage of voltage-gated calcium channels and TRPA1 receptors. Although morphine is a mainstay drug to treat moderate and severe pain related to cancer, it has serious and dose-limiting side effects.
View Article and Find Full Text PDFThe mitochondrial inhibitor 3-nitropropionic acid (3-NP) induces excitotoxicity. The authors hypothesized that CTK 01512-2, a recombinant peptide calcium channel N-type blocker, and the TRPA1 antagonist, could show neuroprotective effects. The male Wistar rats received 3-NP [25 mg/kg (i.
View Article and Find Full Text PDFUnlabelled: Opioids are the first-line treatment for cancer pain. Incomplete pain relief and the high rate of adverse effects of these compounds bring a need to combine them with other drugs acting on different targets.
Aims: We here evaluate the antinociceptive interaction and adverse events of methadone combined with recombinant Phα1β, an analgesic toxin from Phoneutria nigriventer.
This study investigated the effects of intravenous (iv) administration of recombinant Phα1β toxin, pregabalin, and diclofenac by the intrathecal route using an animal model fibromyalgia (FM). The reserpine administration (0.25 mg/kg s.
View Article and Find Full Text PDFAbnormal calcium influx and glutamatergic excitotoxicity have been extensively associated with neuronal death in Huntington's disease (HD), a genetic movement disorder. Currently, there is no effective treatment for this fatal condition. The neurotoxin Phα1β has demonstrated therapeutic effects as a calcium channel blocker, for example during pain control.
View Article and Find Full Text PDFEur J Pharmacol
January 2021
Agents that modulate the activity of high-voltage gated calcium channels (HVCCs) exhibit experimentally and clinically significant effect by relieving visceral pain. Among these agents, the toxins Phα1β and ω-conotoxin MVIIA effectively reduce chronic pain in rodent models. The molecular mechanisms underlying the chronic pain associated with acute pancreatitis (AP) are poorly understood.
View Article and Find Full Text PDFFibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.
View Article and Find Full Text PDFOpioids are the "gold standard" treatment for postoperative pain, but these drugs also have limiting adverse effects. Thus, adjuvant drugs might be useful in opioid therapy for postoperative pain. The aim of the present study was to evaluate the effect of Phα1β, a dual blocker of Cav2 and TRPA1 channels, on antinociceptive and adverse actions of morphine in a model of postoperative pain.
View Article and Find Full Text PDFPurpose: Abdominal hysterectomy is one of the most commonly performed gynecologic surgical procedures and is frequently associated with moderate to severe pain. The present study compared the effects of morphine and ketamine on postoperative analgesia, hemodynamic stability, and postoperative adverse effects in patients who underwent abdominal hysterectomy.
Design: This randomized controlled trial compares the effects of morphine plus adjuvants to those of ketamine plus adjuvants, administered as spinal anesthetic agents in patients who underwent abdominal hysterectomy.
Background: Orofacial pain is clinically challenging, having therapeutic failures and side effects. This study evaluated the antinociceptive activities of the CTK 01512-2 toxin, the TRPA1 channel antagonist, and the selective inhibitor of the N-type voltage-gated calcium channels (N-type VGCC), in different pain models.
Materials And Methods: The trigeminal ganglia were stimulated in vitro with capsaicin.
J Venom Anim Toxins Incl Trop Dis
April 2020
Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients.
View Article and Find Full Text PDFBackground: Diabetic neuropathy is a common cause of painful diabetic neuropathy (PDN). C-X-C chemokine receptor type 4 (CXCR4) expression is increased in peripheral nerve samples from diabetes patients, suggesting a role for CXCR4 in PDN. Therefore, we evaluated the effects of Phα1β, ω-conotoxin MVIIA, and AMD3100 in a model of streptozotocin (STZ)-induced PDN in rodents and naïve model of rats with the activation of the CXCR4/stromal cell-derived factor 1 (SDF-1) signal.
View Article and Find Full Text PDFVascular dementia (VD) is a major cognitive disorder originated from a blood flow disruption in the brain. This process leads to chronic cerebral ischemia that deeply affects neuronal tissues and lipid homeostasis. The understanding of cerebral lipid dynamics during chronic ischemia can reveal biomarkers and novel pharmacological targets for the treatment of VD.
View Article and Find Full Text PDF