Pain
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Among many mechanisms implicated in the development of neuropathic pain after nerve damage is a profound dysfunction of GABAergic inhibitory controls, manifested by ongoing pain, mechanical hypersensitivity, and thermal hyperalgesia. In some respects, neuropathic pain can be considered a "disease" of the nervous system, with features in common with trauma-induced seizures. Indeed, first-line management involves anticonvulsant therapy. ⋯ In related studies, we demonstrated that medial ganglionic eminence cell transplants are also effective in a chronic neuropathic itch model in which there is a significant loss of dorsal horn inhibitory interneurons. Most importantly, in contrast to systemic or intrathecal pharmacological therapies, adverse side effects are minimized when the inhibitory control, namely, γ-aminobutyric acid release, occurs in a spinal cord circuit. These studies suggest that therapy targeted at repairing the GABAergic dysfunction is a viable and novel alternative to the management of neuropathic pain and itch, particularly those that are or become refractory to traditional pharmacotherapy.
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Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. ⋯ In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.
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Editorial Comment
Can patients' daily behaviour patterns contribute to overuse of opioids?