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There has been great development in the testing of invasive and non-invasive neuromodulation for chronic pain. To date, it is known that central and peripheral stimulation targets, combined or not, may influence chronic pain sensation. Although most of the significant results of chronic pain studies come from motor cortex stimulation, novel targets are being explored to increase effect sizes and to induce pain relief in non-responders. Areas covered: In this article, we discuss three emerging targets of non-invasive neuromodulation for chronic pain: (i) a central target: prefrontal cortex stimulation; (ii) a peripheral target: vagal nerve stimulation (VNS); and (iii) a combined peripheral-central target: combination of central and peripheral neural stimulation. Expert commentary: Clinical trials' results on novel targets for chronic pain are at an earlier stage and the mechanisms involved with their combination remain unclear. An important challenge to validate new targets is to determine whether they may be equivalent or even more effective than traditional ones. In spite of the significant advance in this field, especially in refractory chronic pain, mechanistic elements are yet to be comprehended. Thus, exploring multifactorial aspects of novel brain stimulation approaches is fundamental to achieve meaningful results and further augment clinical practice.
Learn More >Social representation theory provides a framework for studying how scientific knowledge affects common sense and communication through inquiries into everyday discourse. This qualitative study examined social representations of chronic pain from 4 sources: North American newspapers; "Chronic Illness Cat" memes from the social media web site, Pinterest; video blogs on YouTube; and from a 2014 film, Cake, and interviews and comments concerning it. Using thematic analysis, we first identified social representations found in our 4 sources and others found in 1 or 2 of them. Second, we analyzed the sources for their rhetorical intentions. Vlogs directly and memes indirectly were first-person accounts, self-authorizing statements of the truth of chronic pain, whereas newspaper articles and the film were third-person accounts of pain, the differences between these perspectives affecting what was said. We conclude that the medium shapes the message.
Learn More >Cognitive biases in attention, interpretation and less consistently memory have been observed in individuals with chronic pain and play a critical role in the onset and maintenance of chronic pain. Despite operating in combination cognitive biases are typically explored in isolation.
Learn More >Central sensitization (CS), a mechanism explaining the persistence of symptoms, has been the focus of many research projects. Explanations given to patients with chronic pain are often based on this mechanism. It is hypothesized that CS also plays an important role in the persistence of medically unexplained symptoms (MUS). However, definitions and operationalizations of CS vary. We conducted a systematic review of definitions, operationalizations and measurement instruments of CS.
Learn More >Optimism and pessimism are related to several mental health and brain disorders, are significant predictors of physical and psychological health outcomes, and implicated as psychosocial determinants of the pain experience. Despite this promising evidence, limited information is available on optimism and pessimism in headache disorders.
Learn More >Diabetic neuropathy is an incapacitating complication in diabetic patients. The cellular and molecular mechanisms involved in this pathology are poorly understood. Previous studies have suggested that the loss of spinal GABAergic inhibition participate in painful diabetic neuropathy. However, the role of extrasynaptic α5 subunit-containing GABAA (α5GABAA) receptors in this process is not known. The purpose of this study was to investigate the role of α5GABAA receptors in diabetes-induced tactile allodynia, loss of rate dependent depression (RDD) of the Hoffmann reflex (HR) and modulation of primary afferent excitability. Intraperitoneal administration of streptozotocin (STZ) induced tactile allodynia. Intrathecal injection of α5GABAA receptor inverse agonist, L-655,708, produced tactile allodynia in naïve rats whereas it reduced allodynia in diabetic rats. In healthy rats, electrical stimulation of the tibial nerve at 5 Hz induced RDD of the HR, although intrathecal treatment with L-655,708 (15 nmol) abolished RDD of the HR. STZ induced the loss of RDD of the HR, while intrathecal L-655,708 (15 nmol) restored RDD of the HR. L-655,708 (15 nmol) increased tonic excitability of the primary afferents without affecting the phasic excitability produced by the primary afferent depolarization. α5GABAA receptors were immunolocalized in superficial laminae of the dorsal horn and L4-L6 DRG. STZ increased mean fluorescence intensity and percentage of neurons expressing α5GABAA receptors in dorsal horn and L4-L6 DRGs in ten-weeks diabetic rats. Our results suggest that spinal α5GABAA receptors modulate the HR, play an antinociceptive and pronociceptive role in healthy and diabetic rats, respectively and are tonically active in primary afferents.
Learn More >Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.
Learn More >Animal models have provided a growing body of information about the pathophysiology of headaches and novel therapeutic targets. In recent years, experiments in awake animals have gained attention as more relevant headache models. Pain can be assessed in animals using behavioral alterations, which includes sensory-discriminative, affective-emotional and cognitive aspects. Spontaneous behavioral alterations such as increased grooming, freezing, eye blinking, wet dog shake and head shake and decreased locomotion, rearing, food or water consumption observed during pain episodes are oftentimes easy to translate into clinical outcomes, but are giving little information about the localization and modality of the pain. Evoked pain response such as tactile and thermal hypersensitivity measures are less translatable but gives more insight into mechanisms of action. Mechanical allodynia is usually assessed with von Frey monofilaments and dynamic aesthesiometer, and thermal allodynia can be evaluated with acetone evaporation test and Hargreaves' test in animal models. Anxiety and depression are the most frequent comorbid diseases in headache disorders. Anxiety-like behaviors are evaluated with the open-field, elevated plus-maze or light/dark box tests. Interpretation of the latter test is challenging in migraine models, as presence of photophobia or photosensitivity can also be measured in light/dark boxes. Depressive behavior is assessed with the forced-swim or tail suspension tests. The majority of headache patients complain of cognitive symptoms and migraine is associated with poor cognitive performance in clinic-based studies. Cluster headache and tension type headache patients also exhibit a reversible cognitive dysfunction during the headache attacks. However, only a limited number of animal studies have investigated cognitive aspects of headache disorders, which remains a relatively unexplored aspect of these pathologies. Thus, the headache field has an excellent and growing selection of model systems that are likely to yield exciting advances in the future.
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