Pain
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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the primary symptoms of MS are losses of sensory and motor functions, it is now recognized that chronic pain is also a major concern affecting between 50% and 80% of MS patients. To date, however, few studies have examined the underlying mechanisms of chronic pain in MS or in the animal model, experimental autoimmune encephalomyelitis (EAE), which shares many features of MS pathology. ⋯ There is, however, a significant influx of CD3+ T cells and increased astrocyte and microglia/macrophage reactivity in the superficial dorsal horn of mice with MOG(35-55) EAE. This suggests that inflammation and reactive gliosis may be key mediators of allodynia in MOG(35-55) EAE similar to peripheral nerve and spinal cord injury models. Taken together, our results show that the MOG(35-55) EAE model is a useful tool to study neuropathic pain in MS.
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Chronic widespread pain (CWP) is associated with poor health-related quality of life (HRQoL). It is unclear whether pain itself is the cause of poor HRQoL or other factors play a role. We hypothesised that new onset of CWP was associated with poor physical and mental HRQoL but that psychosocial risk markers for CWP onset would explain this relationship. ⋯ After adjusting for baseline psychosocial status, the relationship between CWP onset and SF12-MCS was attenuated (RRR=1.2; 95% CI 0.8-1.8), although the association with SF12-PCS remained (RRR=4.8% CI 3.1-7.47). New onset of CWP is associated with poor mental and physical HRQoL. However, the relationship with mental HRQoL is explained by psychosocial risk markers.
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Musculoskeletal pain that affects multiple body sites is typically regarded as comorbidity to single-site pain. Pain present in multiple sites, however, is more severe and disabling compared to single-site pain. This study aimed to prospectively investigate the change in the number of pain sites over 14years, in addition to identifying predictors of multi-site pain. ⋯ However, only sex, age, sleep quality, and educational level remained significant in the final multivariate model after controlling for the number of pain sites at baseline. The final model explained 35% of the variance, of which nearly 80% was accounted for by the number of pain sites at baseline. As the pattern of reporting the number of pain sites appears relatively stable across adulthood and baseline multi-site pain demonstrated strong predictive utility, studies investigating the occurrence of multi-site pain in children and adolescents are recommended to determine potential causal factors contributing to the early course and development of multi-site musculoskeletal 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.