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Background and Objective: Functional magnetic resonance imaging, in conjunction with models of peripheral and/or central sensitization, has been used to assess analgesic efficacy in healthy humans. This review aims to summarize the use of these techniques to characterize brain mechanisms of hyperalgesia/allodynia and to evaluate the efficacy of analgesics. Databases and Data Treatment: Searches were performed (PubMed‐Medline, Cochrane, Web of Science and Clinicaltrials.gov) to identify and review studies. A co‐ordinate based meta‐analysis (CBMA) was conducted to quantify neural activity that was reported across multiple independent studies in the hyperalgesic condition compared to control, using GingerALE software. Results: Of 217 publications, 30 studies met the inclusion criteria. They studied nine different models of hyperalgesia/allodynia assessed in the primary (14) or secondary hyperalgesia zone (16). Twenty‐three studies focused on neural correlates of hyperalgesic conditions and showed consistent changes in the somatosensory cortex, prefrontal cortices, insular cortex, anterior cingulate cortex, thalamus and brainstem. The CBMA on 12 studies that reported activation coordinates for a contrast comparing the hyperalgesic state to control produced six activation clusters (significant at false discovery rate of 0.05) with more peaks for secondary (17.7) than primary zones (7.3). Seven studies showed modulation of brain activity by analgesics in five of the clusters but also in four additional regions. Conclusions: This meta‐analysis revealed substantial but incomplete overlap between brain areas related to neural mechanisms of hyperalgesia and those reflecting the efficacy of analgesic drugs. Studies testing in the secondary zone were more sensitive to evaluate analgesic efficacy on central sensitization at brainstem or thalamocortical levels. Significance: Experimental pain models that provide a surrogate for features of pathological pain conditions in healthy humans and functional imaging techniques are both highly valuable research tools. This review shows that when used together, they provide a wealth of information about brain activity during pain states and analgesia. These tools are promising candidates to help bridge the gap between animal and human studies, to improve translatability and provide opportunities for identification of new targets for back‐translation to animal studies. [ABSTRACT FROM AUTHOR]

Memories of painful events constitute the basis for assessing patients' pain. This study explores the brain oscillatory activity during short‐term memorization of a nociceptive stimulus. High‐density EEG activity (128 electrodes) was recorded in 13 healthy subjects during a match‐to‐sample sensory discrimination task, whereby participants compared the intensity of a thumb‐located electric shock (S2) with a prior stimulus to the same location (S1) delivered 8–10 s earlier. Stimuli were above or below the individual nociceptive threshold. EEG activity with intracortical source localization via LORETA source reconstruction was analysed during the inter‐stimuli period and contrasted with a non‐memory‐related control task. The inter‐stimulus memorization phase was characterized by a focal alpha‐activity enhancement, significant during the nociceptive condition only, which progressed from bilateral occipital regions (cuneus and mid‐occipital gyri) during the first encoding—memorization phase towards the right‐superior and right mid‐temporal gyri during the 2–4 s immediately preceding S2. Initial alpha enhancement in occipital areas/cuneus is consistent with rapid non‐specific inhibition of task‐irrelevant visual processing during initial stimulus encoding. Its transfer to the right‐temporal regions was concomitant to the temporary upholding of the stimulus perceptual representation, previous to receiving S2, and suggests an active and local blockade of external interferences while these regions actively maintain internal information. These results add to a growing field indicating that alpha oscillations, while indicating local inhibitory processes, can also indirectly reveal active stimulus handling, including maintenance in short‐term memory buffers, by objectivizing the filtering out of irrelevant and potentially disrupting inputs in brain regions engaged in internally driven operations. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy using virus‐specific T cells (VST) is a strategy for treating common opportunistic viral infections after transplantation, particularly when these infections do not resolve through antiviral drug therapy. The availability of third‐party healthy donors allows for the immediate use of cells for allogeneic therapy in cases where patients lack an appropriate donor. Here, we present the creation of a cell donor registry of human leukocyte antigen (HLA)‐typed blood donors, REDOCEL, a strategic initiative to ensure the availability of compatible cells for donation when needed. Currently, the registry consists of 597 healthy donors with a median age of 29 years, 54% of whom are women. The most represented blood groups were A positive and O positive, with 36.52% and 34.51%, respectively. Also, donors were screened for cytomegalovirus (CMV) and Epstein–Barr virus (EBV). Almost 65% of donors were CMV‐seropositive, while less than 5% were EBV‐seronegative. Of the CMV‐seropositive donors, 98% were also EBV‐seropositive. High‐resolution HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 allele and haplotype frequencies were determined in the registry. Prevalent HLA alleles and haplotypes were well represented to ensure donor‐recipient HLA‐matching, including alleles reported to present viral immunodominant epitopes. Since the functional establishment of REDOCEL, in May 2019, 87 effective donations have been collected, and the effective availability of donors with the first call has been greater than 75%. Thus, almost 89% of patients receiving an effective donation had available at least 5/10 HLA‐matched cell donors (HLA‐A, ‐B, ‐C, ‐DRB1, and ‐DQB1). To summarize, based on our experience, a cell donor registry from previously HLA‐typed blood donors is a useful tool for facilitating access to VST therapy. [ABSTRACT FROM AUTHOR]

The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre‐stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans‐thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra‐cortical and intra‐thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre‐ and post‐stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement [REM]) sleep. Thalamo‐cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre‐stimulus period. The association between pre‐stimulus widespread increase in thalamo‐cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans‐thalamic transfer of information between cortical areas. [ABSTRACT FROM AUTHOR]

Purpose of review Neuromodulation techniques are being increasingly used to alleviate pain and enhance quality of life. Noninvasive cortical stimulation was originally intended to predict the efficacy of invasive (neurosurgical) techniques, but has now gained a place as an analgesic procedure in its own right. Recent findings Repetitive transcranial magnetic stimulation (rTMS): Evidence from 14 randomised, placebo-controlled trials (~750 patients) supports a significant analgesic effect of high-frequency motor cortex rTMS in neuropathic pain. Dorsolateral frontal stimulation has not proven efficacious so far. The posterior operculo-insular cortex is an attractive target but evidence remains insufficient. Short-term efficacy can be achieved with NNT (numbers needed to treat) ~2-3, but long-lasting efficacy remains a challenge. Like rTMS, transcranial direct-current stimulation (tDCS) induces activity changes in distributed brain networks and can influence various aspects of pain. Lower cost relative to rTMS, few safety issues and availability of home-based protocols are practical advantages. The limited quality of many published reports lowers the level of evidence, which will remain uncertain until more prospective controlled studies are available. Summary Both rTMS and tDCS act preferentially upon abnormal hyperexcitable states of pain, rather than acute or experimental pain. For both techniques, M1 appears to be the best target for chronic pain relief, and repeated sessions over relatively long periods of time may be required to obtain clinically significant benefits. Patients responsive to tDCS may differ from those improved by rTMS. [ABSTRACT FROM AUTHOR]