Brain : a journal of neurology
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The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. ⋯ Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain.
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Chronic pain is a frequent component of many neurological disorders, affecting 20-40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). ⋯ It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain.
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The Na(V)1.7 sodium channel is preferentially expressed within dorsal root ganglion and sympathetic ganglion neurons and their small-diameter peripheral axons. Gain-of-function variants of Na(V)1.7 have recently been described in patients with painful small fibre neuropathy and no other apparent cause. Here, we describe a novel syndrome of pain, dysautonomia, small hands and small feet in a kindred carrying a novel Na(V)1.7 mutation. ⋯ Functional analysis demonstrated that the mutation hyperpolarizes (-9.3 mV) channel activation, depolarizes (+6.2 mV) steady-state fast-inactivation, slows deactivation and enhances persistent current and the response to slow ramp stimuli by 10- to 11-fold compared with wild-type Na(V)1.7 channels. Current-clamp analysis of dorsal root ganglion neurons transfected with G856D mutant channels demonstrated depolarized resting potential, reduced current threshold, increased repetitive firing in response to suprathreshold stimulation and increased spontaneous firing. Our results demonstrate that the G856D mutation produces DRG neuron hyperexcitability which underlies pain in this kindred, and suggest that small peripheral nerve fibre dysfunction due to this mutation may have contributed to distal limb under-development in this novel syndrome.
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Parietofrontal integrity determines neural modulation associated with grasping imagery after stroke.
Chronic stroke patients with heterogeneous lesions, but no direct damage to the primary sensorimotor cortex, are capable of longitudinally acquiring the ability to modulate sensorimotor rhythms using grasping imagery of the affected hand. Volitional modulation of neural activity can be used to drive grasping functions of the paralyzed hand through a brain-computer interface. The neural substrates underlying this skill are not known. ⋯ Finally, estimated white matter microstructure integrity in regions of the contralesional superior longitudinal fascicle adjacent to primary sensorimotor and posterior parietal cortex, as well as grey matter volume co-localized to these specific regions, positively correlated with sensorimotor rhythm modulation leading to successful brain-computer interface control. Thus, volitional modulation of ipsilesional neural activity leading to control of paralyzed hand grasping function through a brain-computer interface after longitudinal training relies on structural and functional connectivity in both ipsilesional and contralesional parietofrontal pathways involved in visuomotor information processing. Extant integrity of this structural network may serve as a future predictor of response to longitudinal therapeutic interventions geared towards training sensorimotor rhythms in the lesioned brain, secondarily improving grasping function through brain-computer interface applications.