Neuroscience letters
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Neuroscience letters · Dec 2013
ReviewVoltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain.
The inflammatory response is a natural response of the body that occurs immediately following tissue damage, which may be due to injury, infection or disease. The acute inflammatory response is an essential mechanism that promotes healing and a key aspect is the ensuing pain, which warns the subject to protect the site of injury. Thus, it is common to see a zone of primary sensitization as well as consequential central sensitization that generally, is maintained by a peripheral drive from the zone of tissue injury. ⋯ The latter has been the main area for trials and use of drugs that modulate ion channels such as carbamazepine and gabapentin, but given the large peripheral drive that follows tissue damage, there is a clear rationale for blocking voltage gated sodium and calcium channels in these pain states. It has been hypothesized that pain of inflammatory origin may evolve into a condition that resembles neuropathic pain, but mixed pains such as low back pain and cancer pain often include elements of both pain states. This review considers the therapeutic potential for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states.
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Neuroscience letters · Dec 2013
ReviewAn industry perspective on the role and utility of animal models of pain in drug discovery.
In recent years, animal behavioral models, particularly those used in pain research, have been increasingly scrutinized and criticized for their role in the poor translation of novel pharmacotherapies for chronic pain. This article addresses the use of animal models of pain from the perspective of industrial drug discovery research. It highlights how, when, and why animal models of pain are used as one of the many experimental tools used to gain better understanding of target mechanisms and rank-order compounds in the iterative process of establishing structure-activity relationships (SAR). ⋯ In addition, the authors discuss some often under-appreciated aspects of currently used (traditional) animal models of pain, including how industry balances efficacy with side effect measures as part of the overall conclusion of efficacy. This is provided to add perspective regarding current efforts to develop new models and endpoints both in rodents and larger animal species as well as assess cognitive and/or affective aspects of pain. Finally, the authors suggest ways in which efficacy evaluation in animal models of pain, whether traditional or new, might better align with clinical standards of analysis, citing examples where applying effect size and NNT estimations to animal model data suggest that the efficacy bar often may be set too low preclinically to allow successful translation to the clinical setting.
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Neuroscience letters · Oct 2012
ReviewCellular and molecular approaches to motor neuron therapy in amyotrophic lateral sclerosis and spinal muscular atrophy.
Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are progressive fatal neurodegenerative diseases. They differ in their disease development but have in common a loss of motor neuron as they progress. Research is ongoing to further understand the origin of these diseases but this common thread of motor neuron loss has provided a target for the development of therapies for both ALS and SMA. It is the linked fields of gene and cell therapy that are providing some of the most interesting therapeutic possibilities.
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Neuroscience letters · Jun 2012
ReviewPain and emotion in the insular cortex: evidence for functional reorganization in major depression.
Major Depressive Disorder (MDD) is among the top causes of disability worldwide and many patients with depression experience pain symptoms. Little is known regarding what makes depressed persons feel like they are in pain. An increasing number of neuroimaging studies show that both physical pain and depression involve the insular cortex. ⋯ Importantly, emotion-related peaks in depressed patients were shifted to the dorsal anterior insula, where regions related to physical pain in healthy subjects are located. This shift was reflected in the observation that median z-coordinates of emotion-related responses in the left hemisphere were significantly larger in depressed patients than in healthy controls. This shift of emotion-related responses to the dorsal insula, i.e., where pain-processing takes place in healthy subjects, may play a role in "emotional allodynia" - a notion that individuals with MDD experience pain in response to stimuli that are normally not painful.
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Neuroscience letters · Jun 2012
ReviewThe use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain.
A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. ⋯ There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today's experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments.