Pain
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Functional reorganisation of the salience network (SN) has been proposed as one of the key pathomechanisms associated with central nociceptive processing in the chronic pain state. Being associated with an altered functional connectivity within the SN, these processes have been hypothesized to result from a loss of inhibitory function leading to node hyperexcitability and spontaneous pain. Combined resting-state BOLD functional magnetic resonance imaging (MRI) and 1 H-MR spectroscopy was applied to chronic back pain patients and healthy subjects to assess deviations from functional integrity (weighted closeness centrality [wCC], derived from resting-state functional MRI), oscillatory BOLD characteristics (spectral power), and neurotransmitter levels (GABA + , glutamate+glutamine) in 2 key SN nodes, anterior insular (aIns R ) and anterior mid-cingulate cortices. ⋯ The aIns R and, to a lesser extent, the anterior mid-cingulate of patients exhibited significantly reduced wCC accompanied by a spectral power shift from a lower to a higher frequency band, indicating a desynchronization of their neuronal activity within the SN, possibly because of increased spontaneous activations. Without revealing neurotransmitter differences, patients alone showed significant positive associations between local GABA + levels and wCC in aIns R , suggesting a stronger dependence of node synchronization on the inhibitory tone in the chronic pain state. However, this needs to be explored in the future using magnetic resonance spectroscopy techniques that are more sensitive to detecting subtle neurotransmitter changes and also allow multifocal characterization of neurotransmitter tone.
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An improved classification of chronic pain is included in the 11 th revision of the International Classification of Diseases and Related Health Problems. For all diagnoses of chronic pain, an optional dimensional code for the chronic pain severity will supplement the categorical diagnoses. Pain severity combines pain intensity, pain-related interference, and pain-related distress. ⋯ The respective NRS ratings showed substantial correlations with the Pain Disability Index score ( r = 0.65) and the FESV subscales ( r = 0.65, r = 0.56, r = 0.37). The extension code for pain severity is a valid and efficient way of recording additional dimensional pain parameters, which can be used to monitor the course of chronic pain and its treatment. The specifier's efficiency makes it possible to use the code when a questionnaire would not be feasible due to time constraints, such as in primary care.
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Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). ⋯ A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.
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Migraine is a complex neurovascular disorder that is one of the leading causes of disability and a reduced quality of life. Even with such a high societal impact, our understanding of the cellular and molecular mechanisms that contribute to migraine headaches is limited. To address this complex disorder, several groups have performed genome-wide association studies to elucidate migraine susceptibility genes, with many identifying transient receptor potential melastatin 8 (TRPM8), a cold-sensitive cation channel expressed in peripheral afferents innervating the trigeminovascular system, and the principal mediator of cold and cold pain associated with injury and disease. ⋯ Our results show that both evoked and spontaneous pain behaviors are dependent on both TRPM8 channels and neurons, as well as required in both acute and chronic migraine models. Moreover, inhibition of TRPM8 channels prevented acute but not established chronic migraine-like pain. These results are consistent with its association with migraine in genetic analyses and establish that TRPM8 channels are a component of the underlying mechanisms of migraine.