Pain
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Randomized Controlled Trial
GDNF levels in the lower lip skin in a rat model of trigeminal neuropathic pain: implications for nonpeptidergic fiber reinnervation and parasympathetic sprouting.
Trigeminal neuropathic pain is associated with trigeminal nerve damage. Significant remodeling of the peripheral nervous system may contribute to the pain; however, the changes and the factors that drive them have not been well described. In this study, a partial injury of the mental nerve of the rat, a purely sensory branch of the trigeminal nerve, resulted in prolonged mechanical allodynia in the lower lip skin persisting up to 4 months. ⋯ Meanwhile, the glial cell line-derived growth factor (GDNF) showed a quick upregulation in the skin after nerve lesioning, with levels peaking at 4 weeks. This suggests that an excess of GDNF in the skin drives the nonpeptidergic C-fiber regeneration and parasympathetic fiber sprouting in the upper dermis, and could be an important mechanism in trigeminal neuropathic pain. This article provides an in-depth description of the changes in nonpeptidergic fibers in the skin after nerve lesioning, and measures, for the first time, GDNF protein levels in the skin after a nerve lesion, providing strong evidence for the role of GDNF in modulating innervation of the nonpeptidergic and parasympathetic fibers in the skin after injury.
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For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. ⋯ This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala.
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Platinum-based anticancer drugs cause neurotoxicity. In particular, oxaliplatin produces early-developing, painful, and cold-exacerbated paresthesias. However, the mechanism underlying these bothersome and dose-limiting adverse effects is unknown. ⋯ Administration of cisplatin evoked mechanical allodynia, an effect that was reduced in TRPA1-deficient mice. TRPA1 is therefore required for oxaliplatin-evoked mechanical and cold hypersensitivity, and contributes to cisplatin-evoked mechanical allodynia. Channel activation is most likely caused by glutathione-sensitive molecules, including reactive oxygen species and their byproducts, which are generated after tissue exposure to platinum-based drugs from cells surrounding nociceptive nerve terminals.
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Lidocaine applied systemically or locally attenuates neuropathic pain in patients. Here we tested the hypothesis that ectopic activity in injured afferent A- or C-fibers is suppressed by lidocaine. In rats the sural nerve (skin nerve) or lateral gastrocnemius-soleus nerve (muscle nerve) was crushed. ⋯ Intravenous application of lidocaine depressed ongoing ectopic activity in A- and C-fibers dose-dependently. Responses to heat or mechanical stimulation of the injured nerve were not suppressed at the highest concentrations of lidocaine. The results support the hypothesis that decrease of neuropathic pain following local or systemic application of a local anesthetic is related to decrease of ectopic ongoing activity in injured afferent nerve fibers.