scholarly journals Drug Management of Visceral Pain: Concepts from Basic Research

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Mellar P. Davis
Keyword(s):  
Clinical Trials ◽  
Neuropathic Pain ◽  
Ion Channels ◽  
Animal Models ◽  
Visceral Pain ◽  
Basic Research ◽  
Kappa Opioid Receptors ◽  
Drug Management ◽  
Kappa Opioid ◽  
Mu Agonists

Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management.

scholarly journals Complex Regional Pain Syndrome (CRPS/RSD) and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

2008 ◽  
Vol 8 ◽  
pp. 229-236 ◽  
Author(s):  
Jennifer Yanow ◽  
Marco Pappagallo ◽  
Letha Pillai
Keyword(s):  
Clinical Trials ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Complex Regional Pain Syndrome ◽  
Bone Pain ◽  
Treatment Options ◽  
Pain Syndrome ◽  
Pain Pathways ◽  
Intravenous Bisphosphonates

Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS) types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.Bisphosphonates have been used for pathologic conditions associated with abnormal bone metabolism, such as osteoporosis, Paget’s disease and cancer-related bone pain for many years. More recently, results of clinical trials have indicated the potential role of bisphosphonates in the treatment of CRPS/RSD.In this paper we will review the preclinical studies regarding the use of bisphosphonates as analgesics in animal models of neuropathic pain, and also summarize the clinical trials that have been done to date. We will give an overview of bisphosphonate pharmacology and discuss several potential mechanisms by which bisphosphonates may be analgesic in CRPS/RSD and bone pain of noncancer origin.

scholarly journals Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with neuropathic pain

2021 ◽  
Author(s):  
Stephanie Shiers ◽  
Hajira Elahi ◽  
Stephanie Hennen ◽  
Theodore J Price
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Mrna Expression ◽  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Visceral Pain ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Mechanical Hypersensitivity

AbstractThe anterior cingulate cortex (ACC) is a critical region of the brain for the emotional and affective components of pain in rodents and humans. Hyperactivity in this region has been observed in neuropathic pain states in both patients and animal models and ablation of this region from cingulotomy, or inhibition with genetics or pharmacology can diminish pain and anxiety. Two adenylyl cyclases (AC), AC1 and AC8 play an important role in regulating nociception and anxiety-like behaviors through an action in the ACC, as genetic and pharmacological targeting of these enzymes reduces mechanical hypersensitivity and anxietylike behavior, respectively. However, the distribution of these ACs in the ACC has not been studied in the context of neuropathic pain. To address this gap in knowledge, we conducted RNAscope in situ hybridization to assess AC1 and AC8 mRNA distribution in mice with spared nerve injury (SNI). Given the key role of AC1 in nociception in neuropathic, inflammatory and visceral pain animal models, we hypothesized that AC1 would be upregulated in the ACC of mice following nerve injury. This hypothesis was also founded on data showing increased AC1 expression in the ACC of mice with zymosan-induced visceral inflammation. We found that AC1 and AC8 are widely expressed in many regions of the mouse brain including the hippocampus, ACC, medial prefrontal cortex and midbrain regions, but AC1 is more highly expressed. Contrary to our hypothesis, SNI causes an increase in AC8 mRNA expression in NMDAR-2B (Nr2b) positive neurons in the contralateral ACC but does not affect AC1 mRNA expression. Our findings show that changes in Adcy1 mRNA expression in the ACC are insufficient to explain the important role of this AC in mechanical hypersensitivity in mice following nerve injury and suggest a potential unappreciated role of AC8 in regulation of ACC synaptic changes after nerve injury.

scholarly journals New molecular targets in angiogenic vessels of glioblastoma tumours

2008 ◽  
Vol 10 ◽  
Author(s):  
Joshua C. Anderson ◽  
Braden C. McFarland ◽  
Candece L. Gladson
Keyword(s):  
Clinical Trials ◽  
Intracranial Pressure ◽  
Animal Models ◽  
Molecular Targets ◽  
Basic Research ◽  
Increased Intracranial Pressure ◽  
Safety And Efficacy ◽  
Antiangiogenic Factors ◽  
New Molecular Targets ◽  
Made In

Antiangiogenesis approaches have the potential to be particularly effective in the treatment of glioblastoma tumours. These tumours exhibit extremely high levels of neovascularisation, which may contribute to their extremely aggressive behaviour, not only by providing oxygenation and nutrition, but also by establishing a leaky vasculature that lacks a blood–brain barrier. This leaky vasculature enables migration of tumour cells, as well as the build up of fluid, which exacerbates tissue damage due to increased intracranial pressure. Here, we discuss the considerable progress that has been made in the identification of the pro- and antiangiogenic factors produced by glioblastoma tumours and the effects of these molecules in animal models of the disease. The safety and efficacy of some of these approaches have now been demonstrated in clinical trials. However, the ability of tumours to overcome these therapies and to re-establish angiogenesis requires further clinical research regarding potential multimodality therapies, as well as basic research into the regulation of angiogenesis by as yet unidentified factors. Optimisation of noninvasive procedures for monitoring of angiogenesis would greatly facilitate such research.

scholarly journals Promoting Gait Recovery and Limiting Neuropathic Pain After Spinal Cord Injury

2016 ◽  
Vol 31 (4) ◽  
pp. 315-322 ◽  
Author(s):  
Catherine Mercier ◽  
Meyke Roosink ◽  
Jason Bouffard ◽  
Laurent J. Bouyer
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Motor Learning ◽  
Clinical Research ◽  
Central Sensitization ◽  
Basic Research ◽  
Gait Rehabilitation ◽  
Cord Injury

Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems. First, the main findings from basic research showing interactions between nociception and learning in the spinal cord will be summarized, focusing both on evidence demonstrating the impact of nociception on motor learning and of motor learning on central sensitization. Then, the generalizability of these findings in animal models to humans will be discussed. Finally, the way potential interactions between nociception and motor learning are currently taken into account in clinical research in patients with spinal cord injury will be presented. To conclude, recommendations will be proposed to better integrate findings from basic research into future clinical research in persons with spinal cord injury.

Blockade of kappa opioid receptors reduces mechanical hyperalgesia and anxiety-like behavior in a rat model of trigeminal neuropathic pain

2022 ◽  
Vol 417 ◽  
pp. 113595
Author(s):  
Joelle de Melo Turnes ◽  
Erika Ivanna Araya ◽  
Amanda Ribeiro Barroso ◽  
Darciane Favero Baggio ◽  
Laura de Oliveira Koren ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Opioid Receptors ◽  
Rat Model ◽  
Mechanical Hyperalgesia ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Trigeminal Neuropathic Pain

CHARACTERIZATION OF KAPPA OPIOID RECEPTORS WITH TRITIATED norBNI

Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 557-560 ◽  
Author(s):  
Á Márki ◽  
F. Ötvös ◽  
G. Tóth ◽  
S. Hosztafi ◽  
A. Borsodi
Keyword(s):  
Opioid Receptors ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid

Berberine: A Promising Natural Isoquinoline Alkaloid for the Development of Hypolipidemic Drugs

2020 ◽  
Vol 20 (28) ◽  
pp. 2634-2647
Author(s):  
Dong-Dong Li ◽  
Pan Yu ◽  
Wei Xiao ◽  
Zhen-Zhong Wang ◽  
Lin-Guo Zhao
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Physicochemical Properties ◽  
Isoquinoline Alkaloid ◽  
Hypolipidemic Activity ◽  
Lipid Lowering ◽  
Lipid Lowering Drug ◽  
Lipid Lowering Agent ◽  
Lowering Drug ◽  
Hypolipidemic Drugs

: Berberine, as a representative isoquinoline alkaloid, exhibits significant hypolipidemic activity in both animal models and clinical trials. Recently, a large number of studies on the lipid-lowering mechanism of berberine and studies for improving its hypolipidemic activity have been reported, but for the most part, they have been either incomplete or not comprehensive. In addition, there have been a few specific reviews on the lipid-reducing effect of berberine. In this paper, the physicochemical properties, the lipid-lowering mechanism, and studies of the modification of berberine all are discussed to promote the development of berberine as a lipid-lowering agent. Subsequently, this paper provides some insights into the deficiencies of berberine in the study of lipid-lowering drug, and based on the situation, some proposals are put forward.

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