Neuroscience
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The transmission of noxious stimuli from peripheral receptors to the cortex involves multiple central ascending pathways. While projections to areas in the brainstem and diencephalon are likely involved in mediating the immediate behavioral responses to pain, the assessment of the sensory and emotional/motivational components of pain are likely processed in parallel ascending pathways that relay in the thalamus on their way to the cerebral cortex. ⋯ In addition, we outline experimental animal and human evidence of functional, anatomical and biochemical alterations in thalamocortical circuits that may be responsible for altered thalamocortical rhythms and the persistent presence of pain following nervous system damage. Finally, we discuss advances in clinical and preclinical development of chronic pain treatments aimed at altering neural and glial function.
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Clinical Trial
The role of sex in sleep deprivation related changes of nociception and conditioned pain modulation.
Sex matters both in the clinical field of pain and sleep medicine. Sleep disturbances are highly prevalent in chronic pain patients and have been shown to deteriorate the pain condition. The pathomechanisms by which insomnia aggravates pain are currently unknown. ⋯ While TSD-induced cold and mechanical hyperalgesia were independent of sex, heat pain thresholds did only significantly decrease in sleep deprived females (p = 0.041). Our results point to a sex specific impact of TSD on descending pain inhibition. In the future, therapeutic strategies for pain patients with co-morbid insomnia may need to more explicitly respect the specific role of sex.
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Controlled Clinical Trial
Inhibition of pain and pain-related brain activity by heterotopic noxious counter-stimulation and selective attention in chronic non-specific low back pain.
The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). ⋯ This indicates that patients with the characteristics described above do not show altered pain inhibitory mechanisms involved in HNCS and selective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits.
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This study aimed to investigate the relation of GABA and glutamate levels in the posterior insula and mechanical pain sensitivity in healthy subjects. Nineteen healthy female individuals underwent single voxel magnetic resonance spectroscopy (MRS) at 3 T. Metabolites were measured in the right posterior insula using MEGA-PRESS spectral editing. ⋯ No significant correlation for pinprick stimuli of lower forces than 256 mN was observed. The results of our study support the hypothesis that excitatory and inhibitory neurotransmitter levels and/or the ratio of glutamate/GABA levels in the posterior insula are related to individual differences in pain sensitivity. These results are in line with chronic pain studies, where elevated glutamate/GABA ratios in the insular cortex of patients with chronic pain syndromes were observed.
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Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. ⋯ In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact.