The Journal of neuroscience : the official journal of the Society for Neuroscience
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Comparative Study
Abnormal Low-Frequency Oscillations Reflect Trait-Like Pain Ratings in Chronic Pain Patients Revealed through a Machine Learning Approach.
Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a sensitive and reliable metric for studying pathological brain mechanisms across various chronic pain patient populations. However, the relationship between pathological brain activity and clinical symptoms are not well defined. Therefore, we used regional BOLD signal variability/amplitude of low-frequency oscillations (LFOs) to identify functional brain abnormalities in the dynamic pain connectome in chronic pain patients that are related to chronic pain characteristics (i.e., pain intensity). ⋯ SIGNIFICANCE STATEMENT Measures of moment-to-moment fluctuations in brain activity of an individual at rest have been shown to be a reliable metric for studying functional brain associated with chronic pain. The current results demonstrate that dysfunction in these intrinsic fluctuations/oscillations in the ascending pain pathway, default mode network, and salience network during resting state display sex differences and can be used to make inferences about trait-like pain intensity ratings in chronic pain patients. These results provide robust and generalizable implications for investigating brain mechanisms associated with longer-lasting/trait-like chronic pain symptoms.
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Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. ⋯ We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.
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Nerve injury-induced hyperactivity of primary sensory neurons in the dorsal root ganglion (DRG) contributes to chronic pain development, but the underlying epigenetic mechanisms remain poorly understood. Here we determined genome-wide changes in DNA methylation in the nervous system in neuropathic pain. Spinal nerve ligation (SNL), but not paclitaxel treatment, in male Sprague Dawley rats induced a consistent low-level hypomethylation in the CpG sites in the DRG during the acute and chronic phases of neuropathic pain. ⋯ We showed that nerve injury caused DNA methylation changes at 8% of CpG sites with prevailing hypomethylation outside of CpG islands in the dorsal root ganglion. Reducing DNA methylation induced pain hypersensitivity, whereas increasing DNA methylation attenuated neuropathic pain. These findings extend our understanding of the epigenetic mechanism of chronic neuropathic pain and suggest new strategies to treat nerve injury-induced chronic pain.
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Cutaneous somatosensory neurons convey innocuous and noxious mechanical, thermal, and chemical stimuli from peripheral tissues to the CNS. Among these are nociceptive neurons that express calcitonin gene-related peptide-α (CGRPα). The role of peripheral CGRPα neurons (CANs) in acute and injury-induced pain has been studied using diphtheria toxin ablation, but their functional roles remain controversial. ⋯ However, they are dispensable for incisional pain transmission. In contrast, peripheral pharmacological inhibition of CGRPα peptide-receptor signaling alleviated the incisional mechanical and heat hypersensitivity, but had no effect on neuropathic pain. These results show that CANs have distinct roles in neuropathic and incisional pain and suggest that their targeting via novel peripheral treatments may selectively alleviate neuropathic versus incisional pain.
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Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents.
There is now compelling evidence that selective stimulation of Aδ nociceptors eliciting first pain evokes robust responses in the primary somatosensory cortex (S1). In contrast, whether the C-fiber nociceptive input eliciting second pain has an organized projection to S1 remains an open question. Here, we recorded the electrocortical responses elicited by nociceptive-specific laser stimulation of the four limbs in 202 humans (both males and females, using EEG) and 12 freely moving rats (all males, using ECoG). ⋯ In this study, C-fibers were activated by radiant heat stimuli delivered to different parts of the body in both humans and rodents while electrical brain activity was recorded. In both species, the C-fiber peripheral input projects to different parts of the contralateral S1, coherently with the representation of the body surface within this brain region. These findings demonstrate that C-fiber input conveys information about the spatial location of noxious stimulation across the body surface, a prerequisite for deploying an appropriate defensive motor repertoire.