Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated channel pacemaker channels in acute and chronic pain models in the rat

Neuroscience ◽  
2007 ◽  
Vol 144 (4) ◽  
pp. 1477-1485 ◽  
Author(s):  
L. Luo ◽  
L. Chang ◽  
S.M. Brown ◽  
H. Ao ◽  
D.H. Lee ◽  
...  
2012 ◽  
Vol 2 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Gordon JG Asmundson ◽  
Holly A Parkerson ◽  
Mark Petter ◽  
Melanie Noel

2019 ◽  
Vol 20 (22) ◽  
pp. 5544 ◽  
Author(s):  
Carmen De Caro ◽  
Claudia Cristiano ◽  
Carmen Avagliano ◽  
Alessia Bertamino ◽  
Carmine Ostacolo ◽  
...  

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.


2021 ◽  
Vol 22 (13) ◽  
pp. 7112
Author(s):  
Barry J. Sessle

Chronic orofacial pain conditions can be particularly difficult to diagnose and treat because of their complexity and limited understanding of the mechanisms underlying their aetiology and pathogenesis. Furthermore, there is considerable variability between individuals in their susceptibility to risk factors predisposing them to the development and maintenance of chronic pain as well as in their expression of chronic pain features such as allodynia, hyperalgesia and extraterritorial sensory spread. The variability suggests that genetic as well as environmental factors may contribute to the development and maintenance of chronic orofacial pain. This article reviews these features of chronic orofacial pain, and outlines findings from studies in animal models of the behavioural characteristics and underlying mechanisms related to the development and maintenance of chronic orofacial pain and trigeminal neuropathic pain in particular. The review also considers the role of environmental and especially genetic factors in these models, focussing on findings of differences between animal strains in the features and underlying mechanisms of chronic pain. These findings are not only relevant to understanding underlying mechanisms and the variability between patients in the development, expression and maintenance of chronic orofacial pain, but also underscore the importance for considering the strain of the animal to model and explore chronic orofacial pain processes.


Author(s):  
Liesbet Goubert ◽  
Rebecca Pillai Riddell ◽  
Laura Simons ◽  
David Borsook

Pain experiences, both acute and chronic, are common in infants, children, and adolescents. The aim of this chapter is to give an overview of different biopsychosocial pediatric pain models that address acute or chronic pain. Recent insights in neural processes are discussed, as well as psychosocial mechanisms across a child’s development. The crucial role of parents in different theoretical conceptualizations is highlighted. We emphasize that both risk factors for the development of chronic pain-related disability and resilience mechanisms for adaptive child functioning should be considered. Finally, clinical implications are outlined ensuing from the different theoretical models discussed in this chapter.


2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Beatrice Mihaela Radu ◽  
Placido Bramanti ◽  
Francesco Osculati ◽  
Maria-Luisa Flonta ◽  
Mihai Radu ◽  
...  

Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU) has been recently proposed. In particular, the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB), two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Maral Tajerian ◽  
J. David Clark

Chronic pain is a highly prevalent and debilitating condition that is frequently associated with multiple comorbid psychiatric conditions and functional, biochemical, and anatomical alterations in various brain centers. Due to its widespread and diverse manifestations, chronic pain is often resistant to classical pharmacological treatment paradigms, prompting the search for alternative treatment approaches that are safe and efficacious. The current review will focus on the following themes: attentional and cognitive interventions, the role of global environmental factors, and the effects of exercise and physical rehabilitation in both chronic pain patients and preclinical pain models. The manuscript will discuss not only the analgesic efficacy of these therapies, but also their ability to reverse pain-related brain neuroplasticity. Finally, we will discuss the potential mechanisms of action for each of the interventions.


2007 ◽  
Author(s):  
Jeffrey I. Gold ◽  
Trina Haselrig ◽  
D. Colette Nicolaou ◽  
Katharine A. Belmont

2019 ◽  
Vol 14 (8) ◽  
pp. 644-653 ◽  
Author(s):  
Jinxuan Ren ◽  
Na Liu ◽  
Na Sun ◽  
Kehan Zhang ◽  
Lina Yu

Chronic pain is a common condition that seriously affects the quality of human life with variable etiology and complicated symptoms; people who suffer from chronic pain may experience anxiety, depression, insomnia, and other harmful emotions. Currently, chronic pain treatments are nonsteroidal anti-inflammatory drugs and opioids; these drugs are demonstrated to be insufficient and cause severe side effects. Therefore, research into new therapeutic strategies for chronic pain is a top priority. In recent years, stem cell transplantation has been demonstrated to be a potent alternative for the treatment of chronic pain. Mesenchymal stem cells (MSCs), a type of pluripotent stem cell, exhibit multi-directional differentiation, promotion of stem cell implantation, and immune regulation; they have also been shown to exert analgesic effects in several chronic pain models. Exosomes produced by MSCs have been demonstrated to relieve painful symptoms with fewer side effects. In this review, we summarize the therapeutic use of MSCs in various chronic pain studies. We also discuss ways to enhance the treatment effect of MSCs. We predict in the future, cell-free therapies for chronic pain will develop from exosomes secreted by MSCs.


Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.


Sign in / Sign up

Export Citation Format

Share Document