Accepted

Neuromodulation for pain has been successfully applied for decades, in that the goals and expectations that patients aim to achieve are clearly described. Nevertheless, the point of view of health care providers is less clear. Therefore, this study aimed to explore the goals, expectations, and definition of success for neuromodulation for pain according to health care providers.

Low back pain is a leading cause of disability worldwide. Intervertebral disc (IVD) degeneration is often associated with low back pain but is sometimes asymptomatic. IVD calcification is an often overlooked disc phenotype that might have considerable clinical impact. IVD calcification is not a rare finding in ageing or in degenerative and scoliotic spinal conditions, but is often ignored and under-reported. IVD calcification may lead to stiffer IVDs and altered segmental biomechanics, more severe IVD degeneration, inflammation and low back pain. Calcification is not restricted to the IVD but is also observed in the degeneration of other cartilaginous tissues, such as joint cartilage, and is involved in the tissue inflammatory process. Furthermore, IVD calcification may also affect the vertebral endplate, leading to Modic changes (non-neoplastic subchondral vertebral bone marrow lesions) and the generation of pain. Such effects in the spine might develop in similar ways to the development of subchondral marrow lesions of the knee, which are associated with osteoarthritis-related pain. We propose that IVD calcification is a phenotypic biomarker of clinically relevant disc degeneration and endplate changes. As IVD calcification has implications for the management and prognosis of degenerative spinal changes and could affect targeted therapeutics and regenerative approaches for the spine, awareness of IVD calcification should be raised in the spine community.

The nature and magnitude of nocebo responses in primary headache disorders are still unknown. To assess the distribution and possible predictors of nocebo responses in primary headache treatments, databases including PubMed, EMBASE, and Cochrane Library were searched from 1988 to 31 December 2020 for parallel-group, double-blind, randomised placebo-controlled trials (RCTs) of pharmacologic treatments of primary headaches. The nocebo responses were calculated using a random effects meta-analysis model. Subgroup and meta-regression analyses were performed to determine the associations of study design and demographic characteristics with nocebo responses. A total of 178 RCTs satisfied the inclusion criteria were included. Prophylactic treatments elicited stronger nocebo responses than acute treatments. The majority of nocebo adverse events (AEs) were mild to moderate in severity, with the nervous and digestive systems being the most commonly affected. There was a strong correlation between the active medication and control groups in terms of AEs, both quantitatively and qualitatively. Long treatment duration, a high proportion of subjects receiving active medications, multicenter design, North America, high body mass index (BMI), females, previous treatment experiences, and a high proportion of migraineurs with aura were all found to be significant positive predictors of nocebo responses, whereas the year of publication was found to be inversely related to them. Nocebo effects should be noticed for their contribution to discontinuation of or lack of adherence to active treatments. Clarifying these nocebo-related risk factors can aid in their clinical prevention and management. This article is protected by copyright. All rights reserved.

Chronic pain is one of the most detrimental symptoms exhibited by cancer patients, being an indication for opioid therapy in up to half of the patients' receiving chemotherapy and in 90% of advanced cases. Various successful non-pharmacological integrative therapy options have been explored and implemented to improve the quality of life in these patients. This review aims to highlight the mechanisms implicated; assessment tools used for cancer pain and summarize current evidence on non-pharmacological approaches in the treatment of chronic cancer pain.

Peripheral neuropathies that occur secondary to nerve injuries may be painful or painless, and including a low-grade inflammation and pro-inflammatory cytokines associated with both regeneration and damage of peripheral nerve cells and fibers. Currently, there are no validated methods that can distinguished between neuropathic pain and painless neuropathy. The aim of this study was to search for proinflammatory and anti-inflammatory proteins associated with pain and experimental pain sensitivity in subjects with surgeon-verified nerve injuries in the upper extremities.