Pain
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Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. ⋯ We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia.
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Nociceptive afferent signaling evoked by inflammation and nerve injury is mediated by the opening of ligand-gated and voltage-gated receptors or channels localized to cholesterol-rich lipid raft membrane domains. Dorsal root ganglion (DRG) nociceptors express high levels of toll-like receptor 4 (TLR4), which also localize to lipid rafts. Genetic deletion or pharmacologic blocking of TLR4 diminishes pain associated with chemotherapy-induced peripheral neuropathy (CIPN). ⋯ Regulation of TRPV1-TLR4 interactions and their associated lipid rafts by AIBP covaried with the enduring reversal of mechanical allodynia otherwise observed in CIPN. In addition, AIBP reduced intracellular calcium in response to the TRPV1 agonist capsaicin, which was increased in DRG neurons from paclitaxel-treated mice and in the naïve mouse DRG neurons incubated in vitro with paclitaxel. Together, these results suggest that the assembly of nociceptive and inflammatory receptors in the environment of lipid rafts regulates nociceptive signaling in DRG neurons and that AIBP can control lipid raft-associated nociceptive processing.
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Controlled Clinical Trial
Aftereffects of alpha transcranial alternating current stimulation over the primary sensorimotor cortex on cortical processing of pain.
Transcranial alternating current stimulation (tACS) is believed to modulate brain oscillations in a frequency-specific manner. Given the correlation between sensorimotor α-oscillations and pain perception, tACS that targets sensorimotor α-oscillations has the potential to reduce pain. Therefore, this study sought to determine the aftereffects of α-tACS over unilateral primary sensorimotor cortex (SM1) on the perceptual and neural responses to noxious painful stimulation of the contralateral hand. ⋯ Moreover, α-tACS decreased the functional connectivity between the targeted SM1 and a network of regions that are crucially involved in pain processing, including the middle cingulate cortex, contralateral somatosensory cortex, and dorsolateral prefrontal cortex. These results demonstrated that after α-tACS applied over the unilateral SM1 does attenuate subsequent neural processing of pain within bilateral sensorimotor regions as well as sensorimotor functional connectivity. The findings provide evidence that sensorimotor α-oscillations directly affect pain processing and support the application of sensorimotor α-tACS for inducing pain analgesia.
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Mild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision. ⋯ White matter measures collected at 6 months after the collision still predicted mTBI pain at that timepoint (n = 36). These white matter connections were associated with 2 nociceptive psychophysical outcomes tested at a remote body site-namely, conditioned pain modulation and magnitude of suprathreshold pain-and with pain sensitivity questionnaire scores. Our findings demonstrate a stable white matter network, the properties of which determine an important amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.
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Meta Analysis
NEUROMUSCULAR ADAPTATIONS TO EXPERIMENTALLY INDUCED PAIN IN THE LUMBAR REGION: SYSTEMATIC REVIEW AND META-ANALYSIS.
Experimental pain models are frequently used to understand the influence of pain on the control of human movement. In this systematic review, we assessed the effects of experimentally induced pain in the lumbar region of healthy individuals on trunk muscle activity and spine kinematics. Databases were searched from inception up to January 31, 2022. ⋯ By contrast, activity of erector spinae, deep multifidus, and transversus abdominis was reduced during postural perturbation tasks. Reduced range of motion of the lumbar spine in the presence of pain was supported by low quality of evidence. Given the agreement between our findings and the adaptations observed in clinical populations, the use of experimental pain models may help to better understand the mechanisms underlying motor adaptations to low back pain.