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The purpose of this narrative review is to discuss current literature about vestibular migraine and other cochleovestibular symptoms related to migraine.
Learn More >The aim of the current study was to determine the clinical characteristics of migraine with aura (MA) as well as the frequency and patterns of perfusion-computed tomography (PCT) alterations, in a series of patients with MA mimicking acute ischemic stroke.
Learn More >The upcoming 11th revision of the International Classification of Diseases (ICD-11) will include a comprehensive classification of chronic pain for the first time, which is based on the biopsychosocial definition of chronic pain. This presents a great opportunity for pain research and clinical practice. The new classification consists of seven main diagnostic categories of chronic pain, which are further divided into increasingly specific levels of diagnoses. Each diagnosis is characterized by clearly defined operationalized criteria. Future users will need to familiarize themselves with the new system and its application. The aim of the present publication is to provide users of the ICD-11 chronic pain classification with answers to frequently asked questions regarding the ICD-11 as a whole, the ICD-11 chronic pain classification, and its application to common pain syndromes. The questions compiled here reached the International Association for the Study of Pain Task Force via different routes (e.g., at conferences, by letter, or during field testing). Furthermore, the authors collected questions posted to the ICD-11 browser and contacted early users of the classification to enquire about their most frequent difficulties when applying the new diagnoses. The authors of the present publication prepared answers to these frequently asked questions. This publication intends to act as a guide for the future users of the new ICD-11 chronic pain classification, hence facilitating its implementation.
Learn More >Neuropathic pain has long-term consequences in terms of affective and cognitive disturbances suggesting the involvement of supraspinal mechanisms. In the present study, we used the spared nerve injury (SNI) model to characterize the development of sensory and aversive components of neuropathic pain, and to determine their electrophysiological impact across PFC and limbic regions. Moreover, we evaluated the regulation of several genes involved in immune response and inflammation triggered by the SNI.We showed that SNI led to sensorial hypersensitivity (cold and mechanical stimuli) and depressive-like behavior lasting 12 months after nerve injury. Interestingly, changes in non-emotional cognitive tasks (novel object recognition and Y maze) showed in 1-month SNI mice, were not evident normal in 12 months-SNI animals. In vivo electrophysiology revealed an impaired the Long Term Potentiation (LTP) at prefrontal cortex (PFC)- nucleus accumbens core (NAcore) pathway in both 1 and 12 months SNI. On the other hand, a reduced neural activity was recorded in the lateral entorhinal cortex (LEC)-dentate gyrus (DG) pathway in 1 month-, but not in 12 months- SNI mice. Finally, we observed the upregulation of specific genes involved in involved in immune response in the hippocampus of 1 month-, but not 12 months-SNI mice, suggesting a neuroinflammatory response which may contribute to the SNI phenotype.These data suggest that distinct brain circuits may drive the psychiatric components of neuropathic pain and pave the way for better investigate the long-term consequences of peripheral nerve injury in which most of the available drugs are to date unsatisfactory.
Learn More >Pain relief remains a significant challenge in the management of irritable bowel syndrome (IBS): "Does anything really help relieve the pain in patients with IBS?". Interventions aimed at pain relief in patients with IBS include diet, probiotics or antibiotics, antidepressants, antispasmodics, and drugs targeting specific gastrointestinal receptors such as opioid or histamine receptors. In the systematic review and meta-analysis published in this journal, Lambarth et al. examined the literature on the role of oral and parenteral anti-neuropathic agents in the management of pain in patients with IBS. This review article appraises their assessment of the efficacy of the anti-neuropathic agents amitriptyline, pregabalin, gabapentin, and duloxetine in the relief of abdominal pain or discomfort, and impact on overall IBS severity and quality of life. This commentary provides an update of current evidence on the efficacy of the dietary and pharmacological treatments that are available or in development, as well psychological and cognitive behavioral therapy for pain in IBS. Advances in recent years augur well for efficacious treatments that may expand the therapeutic arsenal for pain in IBS.
Learn More >Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN). While it is only effective in little more than half of patients, our ability to predict patient response remains incompletely understood. Given that stress exacerbates CIPN, and that the therapeutic effect of duloxetine is thought to be mediated, at least in part, via its effects on adrenergic mechanisms, we evaluated the contribution of neuroendocrine stress axes, sympathoadrenal and hypothalamic-pituitary-adrenal (HPA), to the effect of duloxetine in preclinical models of oxaliplatin- and paclitaxel-induced CIPN. Systemic administration of duloxetine, which alone had no effect on nociceptive threshold, both and mechanical hyperalgesia associated with oxaliplatin- and paclitaxel-CIPN. It more robustly attenuated oxaliplatin CIPN in male rats, while it was more effective for paclitaxel CIPN in females. Gonadectomy attenuated these sex differences in the effect of duloxetine. To assess the role of neuroendocrine stress axes in the effect of duloxetine on CIPN, rats of both sexes were submitted to adrenalectomy combined with fixed level replacement of corticosterone and epinephrine. While CIPN, in these rats, was of similar magnitude to that observed in adrenal-intact animals, rats of neither sex, responded to duloxetine. Furthermore, duloxetine blunted an increase in corticosterone induced by oxaliplatin, and prevented the exacerbation of CIPN by sound stress. Our results demonstrate a role of neuroendocrine stress axes in duloxetine analgesia (anti-hyperalgesia) for the treatment of CIPN.Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating dose-dependent and therapy limiting side-effect of many of the cytostatic drugs used to treat cancer (Argyriou et al., 2010; Marmiroli et al., 2017). Duloxetine is the only treatment for CIPN currently recommended by the American Society of Clinical Oncology (Hershman et al., 2014). In the present study, focused on elucidating mechanisms mediating the response of oxaliplatin- and paclitaxel-induced painful peripheral neuropathy to duloxetine, we demonstrate a major contribution to its effect of neuroendocrine stress axis function. These findings, which parallel the clinical observation that stress may impact response of CIPN to duloxetine (Taylor et al., 2007), open new approaches to the treatment of CIPN and other stress-associated pain syndromes.
Learn More >Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.
Learn More >Many new first-in-class drugs for neuroscience indications have been introduced in the past decade including new treatments for migraine, amyotrophic lateral sclerosis, depression, and multiple sclerosis. However, significant unmet patient needs remain in areas such as chronic pain, neurodegeneration, psychiatric diseases, and epilepsy. This review summarizes some of the advanced clinical compounds for these indications. Additionally, current opportunities and challenges that remain with respect to genetic validation, biomarkers, and translational models are discussed.
Learn More >TRP channels play a central role in the transduction of thermal and nociceptive stimuli by free nerve endings. Most of the research on these channels has been conducted in vitro or in vivo in non-human animals and translation of these results to humans must account for potential experimental biases and interspecific differences. This study aimed at evaluating the involvement of TRPM8, TRPA1 and TRPV1 channels in the transduction of heat and cold stimuli by the human thermonociceptive system. For this purpose, we evaluated the effects of topical agonists of these three channels (menthol, cinnamaldehyde and capsaicin) on the event-related brain potentials (ERPs) elicited by phasic thermal stimuli (target temperatures: 10°C, 42°C, and 60°C) selected to activate cold Aδ thermoreceptors, warm sensitive C thermoreceptors and heat sensitive Aδ polymodal nociceptors. Sixty-four participants were recruited, 16 allocated to each agonist solution group (20% menthol, 10% cinnamaldehyde, 0.025% capsaicin and 1% capsaicin). Participants were treated sequentially with the active solution on one forearm and vehicle only on the other forearm for 20 minutes. Menthol decreased the amplitude and increased the latency of cold and heat ERPs. Cinnamic aldehyde decreased the amplitude and increased the latency of heat but not cold ERPs. Capsaicin decreased the amplitude and increased the latency of heat ERPs and decreased the amplitude of the N2P2 complex of the cold ERPs without affecting the earlier N1 wave or the latencies of the peaks. These findings are compatible with previous evidence indicating that TRPM8 is involved in innocuous cold transduction and that TRPV1 and TRPA1 are involved in noxious heat transduction in humans.
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