Pain
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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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Stress plays a major role in the symptom burden of oncology patients and can exacerbate cancer chemotherapy-induced peripheral neuropathy (CIPN), a major adverse effect of many classes of chemotherapy. We explored the role of stress in the persistent phase of the pain induced by oxaliplatin. Oxaliplatin induced hyperalgesic priming, a model of the transition to chronic pain, as indicated by prolongation of hyperalgesia produced by prostaglandin E 2 , in male rats, which was markedly attenuated in adrenalectomized rats. ⋯ Furthermore, antisense for protein kinase C epsilon, a second messenger involved in type I hyperalgesic priming, also attenuated oxaliplatin-induced hyperalgesic priming. Inhibitors of second messengers involved in the maintenance of type I (cordycepin) and type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN.
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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.