Pain
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Randomized Controlled Trial Multicenter Study Comparative Study
Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies.
We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising candidate neuropathic pain drugs. We evaluated the efficacy of gabapentin or tramadol vs. active placebo (diphenhydramine) in subjects with biopsy-proven painful idiopathic small fiber neuropathy (SFN) who were self-reported gabapentin responders. Eligible subjects entered two single blind run-in phases. ⋯ Eighteen subjects were randomized into the double-blind, crossover phase. There was a significant treatment effect of gabapentin vs. diphenhydramine (p=0.001) and tramadol vs. diphenhydramine (p=0.018) by the before-bed daily pain score averaged over the final 7 days of each treatment period. We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof-of-concept studies.
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Controlled Clinical Trial
Differential brain activation associated with laser-evoked burning and pricking pain: An event-related fMRI study.
An important question remains as to how the brain differentially processes first (pricking) pain mediated by Adelta-nociceptors versus second (burning) pain mediated by C-nociceptors. In the present cross-over randomized, within-subjects controlled study, brain activity patterns were examined with event-related fMRI while pricking and burning pain were selectively evoked using a diode laser. Stimuli evoking equivalent pain intensities were delivered to the dorsum of the left foot. ⋯ Stronger activation in the pricking pain condition was found in the ipsilateral hippocampus, bilateral parahippocampal gyrus, bilateral fusiform gyrus, contralateral cerebellum and contralateral cuneus/parieto-occipital sulcus. Stronger activation in the burning pain condition was found in the ipsilateral dorsolateral prefrontal cortex. These differential activation patterns suggest preferential importance of Adelta-fiber signals versus C-fiber signals for these specific brain regions.
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Parkinson's disease is a chronic, progressive, incurable neurodegenerative disease. As the disease progresses, motor disturbances and non-motor symptoms represent considerable illness burdens. Symptom relief is the goal for the treatment. ⋯ Pain is frequent and disabling, independent of demographic and clinical variables except for female gender, and is significantly more common in Parkinson's patients compared to the general population. A minority of the Parkinson's disease patients with pain received analgesic medication. The findings call for improved attention to assessment and treatment of pain in the follow-up of Parkinson's disease patients.
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Controlled Clinical Trial
Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain.
Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity, controversy exists over which genes are involved. While recent data suggest a "protective" (i.e., less pain) haplotype in the GTP cyclohydrolase (GCH1) gene, other research has failed to confirm this association. Possibly, the effects of single nucleotide polymorphisms (SNPs) vary depending on the pain task. ⋯ Each of the GCH1 polymorphisms was associated with lower pain ratings. When combined, three of the five accounted for a surprisingly high 35% of the inter-individual variance in pain ratings. We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin.
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This study examined the role of pain catastrophizing, fear of movement and depression as determinants of repetition-induced summation of activity-related pain. The sample consisted of 90 (44 women and 46 men) work-disabled individuals with chronic low back pain. Participants were asked to lift a series of 18 canisters that varied according to weight (2.9kg, 3.4kg, 3.9kg) and distance from the body. ⋯ Fear of movement, but not pain catastrophizing or depression, was associated with greater repetition-induced summation of pain. The findings point to possible neurophysiological mechanisms that could help explain why fear of pain is a robust predictor of pain-related disability. Mechanisms of repetition-induced summation of activity-related pain are discussed.