Accepted

Pain score, functional disability, and health-related quality of life (HRQoL) are core outcome domains for chronic pain clinical trials. Although greater levels of pain reduction have been shown to be linked to larger gains in HRQoL, little is known of the association between HRQoL and disability in the setting of chronic pain. The aims of this study were to 1) investigate the association between functional disability and HRQoL and 2) estimate the utility values associated with levels of functional disability in patients treated with evoked compound action potential (ECAP) spinal cord stimulation (SCS) for chronic pain.

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2-3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL-6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and PET-CT are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15-25 mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC related comorbidities, such as diabetes and osteoporosis, and there is limited data on the use of disease-modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment. This article is protected by copyright. All rights reserved.

External low-frequency peripheral nerve stimulation (LFS) has been proposed as a novel method for neuropathic pain relief. Previous studies have reported that LFS elicits long-term depression-like effects on human pain perception when delivered at noxious intensities, while lower intensities are ineffective. To shed light on cortical regions mediating the effects of LFS, we investigated changes in somatosensory-evoked potentials (SEPs) during four LFS intensities. LFS was applied to the radial nerve (600 pulses, 1 Hz) of twenty-four healthy participants at perception (1×), low (5×), medium (10×) and high intensities (15× detection threshold). SEPs were recorded during LFS, and averaged SEPs in 10 consecutive one-minute epochs of LFS were analysed using source dipole modelling. Changes in resting electroencephalography (EEG) were investigated after each LFS block. Source activity in the midcingulate cortex (MCC) decreased linearly during LFS, with greater attenuation at stronger LFS intensities, and in the ipsilateral operculo-insular cortex during the two lowest LFS stimulus intensities. Increased LFS intensities resulted in greater augmentation of contralateral primary sensorimotor cortex (SI/MI) activity. Stronger LFS intensities were followed by increased alpha (9-11 Hz) band power in SI/MI and decreased theta (3-5 Hz) band power in MCC. Intensity-dependent attenuation of MCC activity with LFS is consistent with a state of long-term depression. Sustained increases in contralateral SI/MI activity suggests that effects of LFS on somatosensory processing may also be dependent on satiation of SI/MI. Further research could clarify if the activation of SI/MI during LFS competes with nociceptive processing in neuropathic pain.