Luis Garcia-Larrea

Considerable progress has been made over the past decade in the use, practicality, and clinical relevance of electroencephalography (EEG) and magnetoencephalography (MEG)-derived data, improving our understanding of cortical nociceptive processing, the transition from nociception to conscious pain, and its cognitive–emotional modulations. Multimodal responses to heat, cold, and tactile/electrical stimuli, combined with autonomic reactions, provide objective sensory tests that bypass the limitations of verbal responses, while emerging approaches to spontaneous EEG/MEG analysis are changing the game in the still elusive area of ongoing pain. We can expect that all departments involved in the assessment of chronic pain will gradually be able to access these powerful and flexible techniques.

This study shows in healthy human volunteers that two sessions of high-frequency electrical stimulation of the skin (HFS) separated by 1 hour induce longer-lasting secondary hyperalgesia as compared to a single session matched in terms of the number of HFS pulses. This finding suggests that repeated exposures to noxious stimulation can favor the induction of a longer-lasting form of central sensitization.

Background: Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce ‘research waste’, improve the effectiveness of pain research and therapy and promote the uptake of research evidence. In this study, the European Pain Federation (EFIC) developed a Pain Research Strategy for Europe.Methods: The study used multiple methods, including literature searches, multidisciplinary expert debate, a survey and a final consensus meeting. The cross‐sectional survey was conducted among 628 European pain researchers, clinicians, educators and industry professionals to obtain the rating and hierarchy of pain research priorities.The final consensus meeting involved a multidisciplinary expert panel including people with lived experience from 23 countries. The survey results guided discussions where top priorities were agreed.Results: Content analysis identified nine survey themes, of which five emerged as top priorities: (i) understand the pathophysiology of pain; (ii) understand and address comorbidities; (iii) critically assess current therapies; (iv) develop new treatments; and (v) explore the biopsychosocial impacts of pain. Physical, psychological and social approaches were prioritized at the same level as pharmacological treatments. The top priorities were endorsed by a multidisciplinary expert panel. The panel emphasized the importance of also clearly communicating the concepts of prediction, prevention self‐management and personalized pain management in the final strategy.Conclusions: The content of the final top research priorities' list reflects a holistic approach to pain management. The equal importance given to physical, psychological and social aspects alongside pharmacological treatments highlights the importance of a comprehensive biopsychosocial‐orientated research strategy. The expert panel's endorsement of five top priorities, coupled with an emphasis on communicating the concepts of prediction, prevention, self‐management and personalized pain management, provides a clear direction for future basic, translational and clinical research.Significance: EFIC has developed a Pain Research Strategy for Europe that identifies pain research areas deserving the most focus and financial support. Implementation and wide dissemination of this Strategy is vital to increase the conduct of urgent pain projects, pain research funding and the implementation of research findings into practice, to ultimately decrease the personal, societal and financial burden of pain.

Introduction: The ability of repetitive transcranial magnetic stimulation (rTMS) to deliver a magnetic field (MF) in deep brain targets is debated and poorly documented. Objective: To quantify the decay of MF in the human brain. Methods: Magnetic field was generated by single pulses of TMS delivered at maximum intensity using a flat or angulated coil. Magnetic field was recorded by a 3D-magnetic probe. Decay was measured in the air using both coils and in the head of 10 postmortem human heads with the flat coil being positioned tangential to the scalp. Magnetic field decay was interpreted as a function of distance to the coil for 6 potential brain targets of noninvasive brain stimulation: the primary motor cortex (M1, mean depth: 28.5 mm), dorsolateral prefrontal cortex (DLPFC: 28 mm), secondary somatosensory cortex (S2: 35.5 mm), posterior and anterior insulae (PI: 38.5 mm; AI: 43.5 mm), and midcingulate cortex (MCC: 57.5 mm). Results: In air, the maximal MF intensities at coil center were 0.88 and 0.77 T for the flat and angulated coils, respectively. The maximal intracranial MF intensity in the cadaver model was 0.34 T, with a ∼50% decay at 15 mm and a ∼75% MF decay at 30 mm. The decay of the MF in air was similar for the flat coil and significantly less attenuated with the angulated coil (a ∼50% decay at 20 mm and a ∼75% MF decay at 45 mm). Conclusions: Transcranial magnetic stimulation coil MFs decay in brain structures similarly as in air, attenuation with distance being significantly lower with angulated coils. Reaching brain targets deeper than 20 mm such as the insula or Antérior Cingulate Cortex seems feasible only when using angulated coils. The abacus of MF attenuation provided here can be used to adjust modalities of deep brain stimulation with rTMS in future research protocols.

Purpose of review: Neuromodulation techniques are being increasingly used to alleviate pain and enhance quality of life. Non-invasive 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.