Browse by Audience
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequently reported adverse effects of cancer treatment. CIPN often persists long after treatment completion and has detrimental effects on patient's quality of life. There are no efficacious FDA-approved drugs for CIPN. We recently demonstrated that nasal administration of mesenchymal stem cells (MSC) reverses the cognitive deficits induced by cisplatin in mice. Here we show that nasal administration of MSC after cisplatin- or paclitaxel treatment- completely reverses signs of established CIPN, including mechanical allodynia, spontaneous pain, and loss of intraepidermal nerve fibers (IENF) in the paw. The resolution of CIPN is associated with normalization of the cisplatin-induced decrease in mitochondrial bioenergetics in DRG neurons. Nasally administered MSC enter rapidly the meninges of the brain, spinal cord and peripheral lymph nodes to promote IL-10 production by macrophages. MSC mediated resolution of mechanical allodynia recovery of IENFs and restoration of DRG mitochondrial function critically depends on IL-10 production. MSC from IL-10 knockout animals are not capable of reversing the symptoms of CIPN. Moreover WT MSC do not reverse CIPN in mice lacking IL-10 receptors on peripheral sensory neurons. In conclusion only two nasal administrations of MSC fully reverse CIPN and the associated mitochondrial abnormalities via an IL-10 dependent pathway. Since MSC are already applied clinically we propose that nasal MSC treatment could become a powerful treatment for the large group of patients suffering from neurotoxicities of cancer treatment.
Learn More >Early life stress is known to affect the development of the nervous system and its function at a later age. It increases the risk to develop psychiatric disorders as well as chronic pain and its associated affective comorbidities across the lifespan. GABAergic inhibition is important for the regulation of central function and related behaviors, including nociception, anxiety or social interactions, and requires low intracellular chloride levels. Of particular interest, the oxytocinergic (OTergic) system exerts potent anxiolytic, analgesic and pro-social properties and is known to be involved in the regulation of chloride homeostasis and to be impaired following early life stress.
Learn More >Opioid abuse has devastating effects on patients, their families, and society. Withdrawal symptoms are severely unpleasant, prolonged, and frequently hinder recovery or lead to relapse. The sharp increase in abuse and overdoses arising from the illicit use of potent and rapidly-acting synthetic opioids, such as fentanyl, highlights the urgency of understanding the withdrawal mechanisms related to these drugs. Progress is impeded by inconsistent reports on opioid withdrawal in different preclinical models. Here, using rats and mice of both sexes, we quantified withdrawal behaviors during spontaneous and naloxone-precipitated withdrawal, following two weeks of intermittent fentanyl exposure. We found that both mice and rats lost weight during exposure and showed increased signs of distress during spontaneous and naloxone precipitated withdrawal. However, these species differed in their expression of withdrawal associated pain, a key contributor to relapse in humans. Spontaneous or ongoing pain was preferentially expressed in rats in both withdrawal conditions, while no change was observed in mice. In contrast, withdrawal associated thermal hyperalgesia was found only in mice. These data suggest that rats and mice diverge in how they experience withdrawal and which aspects of the human condition they most accurately model. These differences highlight each species' strengths as model systems and can inform experimental design in studies of opioid withdrawal.
Learn More >The main function of pain is to automatically draw attention towards sources of potential injury. However, pain sometimes needs to be inhibited in order to address or pursue more relevant tasks. Elucidating the factors that influence how people manage this relationship between pain and task performance is essential to understanding the disruptive nature of pain and its variability between individuals. Here, 41 healthy adults completed a challenging working memory task (2-back task) while receiving painful thermal stimulations. Examining the trial-by-trial relationship between pain perception and task performance revealed that pain's disruptive effects on performance were mediated by self-reported pain intensity, and that the analgesic effects of a competing task were influenced by task performance. We found that higher pain catastrophizing, higher trait anxiety, and lower trait mindfulness were associated with larger trade-offs between pain perception and task performance, suggesting that these psychological factors can predict increased fluctuations between disruption by pain and analgesia from a competing task. Altogether these findings provide an important and novel perspective on our understanding of individual differences in the interplay between pain and ongoing task performance.
Learn More >Myofascial pain syndrome (MPS) is a prevalent chronic pain disorder primarily characterized by myofascial trigger points (MTrPs). There is limited knowledge on the pathophysiology and mechanisms underlying MTrP and its development. Research has previously demonstrated the identification of MTrPs using ultrasound and vibration sonoelastography, although there is some contradictory evidence regarding if MTrPs present as hyper or hypoechoic regions. Electromyography (EMG) investigations of MTrP have demonstrated that MTrPs are usually located proximal to innervation zones where the peak surface EMG signals are obtained from. Central sensitization has been proposed as the primary mechanism underlying MTrP development. Central sensitization is associated with hyperexcitability of neuronal responses to normal or noxious stimuli. There is a need for a study that measures ultrasound image textural changes and motor unit activity responses in the muscle following sensitization. The purpose of this study is to determine whether sensitizing healthy muscle using capsaicin induces a regional change in image texture variables within the specific and surrounding muscles, as well as the motor unit frequency and amplitude changes that accompany them. This is an exploratory trial that aims to provide preliminary evidence on whether central sensitization is a direct cause of taut band and MTrP development.
Learn More >Chronic nonspecific low back pain (LBP) is very common; it is defined as pain without a recognizable etiology that lasts for more than three months. Some clinical practice guidelines suggest that acupuncture can offer an effective alternative therapy. This review is a split from an earlier Cochrane review and it focuses on chronic LBP.
Learn More >Empathy for pain allows one to recognize, understand, and respond to another person's pain in a prosocial manner. Young children develop empathy for pain later than empathy for other negative emotions (e.g., sadness), which may be due to social learning. How parents reminisce with children about past painful events has been linked to children's pain cognitions (e.g., memory) and broader socioemotional development. The present study examined how parent-child reminiscing about pain may be linked to children's empathic behaviors toward another person's pain.
Learn More >Previous studies suggested that Cg1 area of the cingulate cortex of rats controls glutamate-mediated fear-induced defensive behaviour and antinociception organised at the posterior hypothalamus. In turn, microinjection of the nitric oxide donor SIN-1 into the anterior hypothalamus of mice produced defensive behaviours and fear-induced antinociception. However, it remains unknown whether Cg1 also modulates the latter mechanisms in mice.
Learn More >Centrally administered bombesin induces scratching and grooming in rats. These behaviors were blocked by early benzomorphan kappa opioid receptor (KOR) agonists as reported by Gmerek and Cowan in 1984. This was the first evidence that KORs may be involved in the sensation of itch-like behaviors. Subsequent development of additional animal models for acute and chronic itch has led to important discoveries since then. For example, it was found that (a) gastrin-releasing peptide (GRP), natriuretic polypeptide b and their cognate receptors are keys for the transmission of itch sensation at the spinal cord level, (b) dynorphins (Dyns), the endogenous KOR agonists, work as inhibitory neuromodulators of itch at the spinal cord level, (c) in a mouse model for acute itch, certain KOR antagonists elicit scratching, (d) in mouse models of acute or chronic itch, KOR agonists (e.g., U50,488, nalfurafine, CR 845, nalbuphine) suppress scratching induced by different pruritogens, and (e) nalfurafine, CR 845, and nalbuphine are in the clinic or in clinical trials for pruritus associated with chronic kidney disease and chronic liver disease, as well as pruritus in chronic skin diseases.
Learn More >