Human Studies

High frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization (CS), manifested as increased pinprick sensitivity of the skin surrounding the site of HFS. Our aim was to assess the effect of CS on pinprick-evoked pupil dilation responses (PDRs) and pinprick-evoked brain potentials (PEPs). We hypothesized that the increase in the positive wave of PEPs following HFS would result from an enhanced pinprick-evoked phasic response of the locus coeruleus-noradrenergic system (LC-NS), indicated by enhanced PDRs. In fourteen healthy volunteers, 64 and 96 mN pinprick stimuli were delivered to the left and right forearms, before and twenty minutes after applying HFS to one of the two forearms. Both PEPs and pinprick-evoked PDRs were recorded. After HFS, pinprick stimuli were perceived as more intense at the HFS treated arm compared to baseline and control site, and this increase was similar for both stimulation intensities. Importantly, the pinprick-evoked PDR was also increased and the increase was stronger for 64 as compared to 96 mN stimulation. This is in line with our previous results showing a stronger increase of the PEP positivity at 64 vs. 96 mN stimulation and suggests that the increase in PEP positivity observed in previous studies could relate, at least in part, to enhance LC-NS activity. However, there was no increase of the PEP positivity in the present study, indicating that enhanced LC-NS activity is not the only determinant of the HFS-induced enhancement of PEPs. Altogether, our results indicate that PDRs are more sensitive for detecting CS than PEPs.

Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.

Chronic noncancer pain is a leading cause of sickness absence (SA) and disability pension (DP). The objectives of this study were to identify trajectories of SA/DP before and after strong and weak opioid initiation for noncancer pain and the factors associated with these trajectories. A longitudinal population-based study of 201,641 people (24-59 years) without cancer who initiated opioid analgesics in 2009 in Sweden was conducted. Trajectories of net annual SA/DP days in the 5 years before/after opioid initiation were estimated with group-based trajectory modelling. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with trajectory groups. Among the 6.9% of people initiating strong opioids, 12.5% had persistent high SA/DP (estimated 320 days/year) before and after opioid initiation and 72.9% had persistent low/minimum SA/DP (estimated 30 days/year). Approximately 8.6% of people had increasing SA/DP, and 6.1% had decreasing SA/DP after opioid initiation, although this seemed to reflect continuation of preinitiation patterns. Trajectories were similar at lower SA/DP days/year among those initiating weak opioids. Persistent high SA/DP among strong opioid initiators were associated with ≥5 comorbidities (OR = 8.72, 95% CI 5.61-13.56), ≤9 years of education (OR = 5.83, 95% CI 4.84-7.03), and previous use of antidepressants (OR = 4.57, 95% CI 3.89-5.37) and antipsychotics (OR = 4.49, 95% CI 2.93-6.88). Three-quarters of people initiating opioids for noncancer pain had persistent low/minimum levels of SA/DP 5 years before and after initiation. Increasing and decreasing SA/DP after opioid initiation seemed to reflect a continuation of preinitiation patterns. Our findings highlight the complex range of sociodemographic and medication-related factors associated with persistent SA/DP.

To compare the analgesic effects of stimulation of the anterior cingulate cortex (ACC) or the posterior superior insula (PSI) against sham deep (d) repetitive (r) transcranial magnetic stimulation (TMS) in patients with central neuropathic pain (CNP) after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study.