Pain
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Meta Analysis
Placebo effects on cutaneous pain and itch: a systematic review and meta-analysis of experimental results and methodology.
Placebo effects, positive treatment outcomes that go beyond treatment processes, can alter sensations through learning mechanisms. Understanding how methodological factors contribute to the magnitude of placebo effects will help define the mechanisms by which these effects occur. We conducted a systematic review and meta-analysis of experimental placebo studies in cutaneous pain and itch in healthy samples, focused on how differences in methodology contribute to the resulting placebo effect magnitude. ⋯ Other methodological and demographic factors did not significantly affect placebo magnitudes. Placebo effects on pain and itch reliably occur in experimental settings with varied methods, and conditioning with verbal suggestion produced the strongest effects. Although methods may shape the placebo effect to some extent, these effects appear robust overall, and their underlying learning mechanisms may be harnessed for applications outside the laboratory.
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Reliable and objective biomarkers promise to improve the assessment and treatment of chronic pain. Resting-state electroencephalography (EEG) is broadly available, easy to use, and cost efficient and, therefore, appealing as a potential biomarker of chronic pain. However, results of EEG studies are heterogeneous. ⋯ Risk of bias was high in many studies and domains. Together, this systematic review synthesizes evidence on how resting-state M/EEG might serve as a diagnostic biomarker of chronic pain. Beyond, this review might help to guide future M/EEG studies on the development of pain biomarkers.
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Repeated stress produces hyperalgesic priming in preclinical models, but underlying mechanisms remain uncertain. As stress engages kappa opioid receptors (KORs), we hypothesized that repeated administration of KOR agonists might mimic, in part, stress-induced hyperalgesic priming. The potential contribution of circulating prolactin (PRL) and dysregulation of the expression of PRL receptor (PRLR) isoforms in sensory neurons after KOR agonist administration was also investigated. ⋯ Umbellulone-induced allodynia was prevented by cabergoline co-treatment during priming with KOR agonists in female, but not male, mice. Hyperalgesic priming therefore occurs in both sexes after either biased or nonbiased KOR agonists. However, a PRL/PRLR-dependence is observed only in female nociceptors possibly contributing to pain in stress-related pain disorders in females.
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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.