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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Randomized Controlled Trial
Induction of nocebo and placebo effects on itch and pain by verbal suggestions.
Physical complaints, such as pain, can be effectively reduced by placebo effects through induction of positive expectations, or increased by nocebo effects through induction of negative expectations. In the present study, verbally induced nocebo and placebo effects on itch were experimentally investigated for the first time. In part 1, the role of verbal suggestions in inducing nocebo effects on itch and pain was investigated. ⋯ In part 2, verbal suggestions designed to produce a placebo effect on itch (itch placebo) or pain (pain placebo), or neutral suggestions (itch placebo control and pain placebo control) were given regarding a second application of histamine and compared with the first application applied in part 1. Results of placebo effects only showed a significantly larger decrease in itch in the itch placebo condition than in the pain placebo condition. In conclusion, we showed for the first time that nocebo and possibly placebo responses can be induced on itch by verbal suggestions.
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Randomized Controlled Trial
Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia.
We assessed for the first time the long-term maintenance of repetitive transcranial magnetic stimulation (rTMS)-induced analgesia in patients with chronic widespread pain due to fibromyalgia. Forty consecutive patients were randomly assigned, in a double-blind fashion, to 2 groups: one receiving active rTMS (n=20) and the other, sham stimulation (n=20), applied to the left primary motor cortex. The stimulation protocol consisted of 14 sessions: an "induction phase" of 5 daily sessions followed by a "maintenance phase" of 3 sessions a week apart, 3 sessions a fortnight apart, and 3 sessions a month apart. ⋯ Active rTMS significantly reduced pain intensity from day 5 to week 25. These analgesic effects were associated with a long-term improvement in items related to quality of life (including fatigue, morning tiredness, general activity, walking, and sleep) and were directly correlated with changes in intracortical inhibition. In conclusion, these results suggest that TMS may be a valuable and safe new therapeutic option in patients with fibromyalgia.
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We hypothesised that the relative importance of physical and psychological risk factors for mechanical low back pain (LBP) might differ importantly according to whether there is underlying spinal pathology, psychological risk factors being more common in patients without demonstrable pathology. If so, epidemiological studies of LBP could benefit from tighter case definitions. To test the hypothesis, we used data from an earlier case-control study on patients with mechanical LBP who had undergone magnetic resonance imaging (MRI) of the lumbosacral spine. ⋯ Radiation of pain below the knee (280 patients) and weakness or numbness below the knee (257 patients) were both associated with nerve root deviation/compression (OR 2.5, 95% CI 1.4 to 4.5; and OR 1.8, 95% CI 1.1 to 3.1, respectively). However, we found no evidence for the hypothesised differences in risk factors between patients with and without demonstrable spinal pathology. This suggests that when researching the causes and primary prevention of mechanical LBP, there may be little value in distinguishing between cases according to the presence or absence of the more common forms of potentially underlying spinal pathology.
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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.