Accepted

This literature review summarizes the role of plant-based foods and diet quality in osteoarthritis, particularly knee osteoarthritis, in observational studies and clinical trials published during 2015- 2020. The included studies have suggested favorable results on reducing the prevalence, pain, and cartilage changes related to osteoarthritis and inflammatory and oxidation markers such as inter- leukin-1, interleukin-6, tumor necrosis factor, and lipid peroxidation. Due to the lack of large lon- gitudinal cohorts to study whole foods or diets concerning knee osteoarthritis, findings from the cross-sectional studies or clinical trials require further validation, particularly in well-designed clinical trials and a more extended follow-up period. Potential mechanisms on the role of plant-based foods in body weight, inflammation, and microbiome were explored to explain their protective associations with osteoarthritis. However, most evidence examining the relationship between the microbiome and osteoarthritis joint pain is conducted in preclinical animal studies, and few observational studies show a positive association between Streptococcus species and local joint inflammation in the knee. Given the close links of plant-based foods on obesity, inflammation, and microbiome, data on the role of whole foods or diets in the change in knee osteoarthritis pain through the lens of microbial composition can provide more certainty regarding the utilization of microbiome as a potential thera- peutic target.

Hip fractures are debilitating in older adults because of their impact on quality of life. Opioids are associated with adverse effects in this population, so oral acetaminophen is commonly prescribed to minimize opioid use. Intravenous (iv) acetaminophen has been reported to have superior efficacy and bioavailability than oral acetaminophen. Nevertheless, its effect on postoperative outcomes in emergency hip fractures is unclear. This systematic review assessed the effect of iv acetaminophen on postoperative outcomes in older hip fracture patients.

After an interpretation trajectory, the Dutch Quality of Healthcare Institute recommended that for five indications, spinal cord stimulation, dorsal root ganglion stimulation, or occipital nerve stimulation, together referred to as neurostimulation, can be considered effective and be reimbursed in the Netherlands. These five indications are the well and largely studied, accepted neurostimulation indications in scientific literature. As an extension of this, all the scientific societies involved in the Netherlands were required to reach a consensus about the diagnosis and treatment of these five formulated indications to describe the place of neurostimulation within the treatment algorithm. This article describes the development process and content of the consensus paper.

Dysmenorrhea is characterized by high rates of transition to chronic pain. In a previous study using structural equation modeling we demonstrated that several symptom domains associated with the emerging concept of nociplastic pain can be described using two symptom groups: generalized sensory sensitivity (GSS; composed of widespread pain, interceptive sensitivity, and environmental sensitivity) and SPACE (composed of unrefreshing Sleep, Pain, Affective disturbances, Cognitive issues, and reduced Energy). Here we perform a secondary cross-sectional analysis examining the same symptoms groups in a cohort of dysmenorrhea patients without a diagnosis of chronic pain. Our purpose is to determine if the same symptom patterns are apparent, and if they are associated with the presence and severity of comorbid pain. Participants were 201 women with dysmenorrhea. We replicated the hypothesized two-factor structure in this cohort (comparative fit index = .971, root mean square error of approximation =.055; 90% CI: .000, .097). GSS was associated with the severity of bladder, bowel, and overall pain in multivariable models including SPACE, patient age, and BMI (all β > .32, all p < .05). SPACE was associated with menstrual pain during NSAID use, while GSS was associated with the same in the absence of NSAID use (both p < .05). This two-factor model of symptoms appears to be replicable and valid in a cohort of women at risk for developing chronic pain conditions. These symptom groups are promising potential markers of future pain chronification and may point to patients in need of earlier or more aggressive intervention.

G protein-coupled receptors (GPCRs) are currently appreciated to be routed to diverse cellular platforms to generate both G protein-dependent and -independent signals. The latter has been best studied with respect to β-arrestin-associated receptor internalization and trafficking to signaling endosomes for extracellular signal-regulated kinase (ERK) activation. However, how GPCR structural and conformational variants regulate endosomal ERK signaling dynamics, which can be central in neural development, plasticity, and disease processes, is not well understood. Among class B GPCRs, the PACAP-selective PAC1 receptor is unique in the expression of variants that can contain intracellular loop 3 (ICL3) cassette inserts. The nervous system expresses preferentially the PAC1Null (no insert) and PAC1Hop (28-amino acid Hop insert) receptor variants. Our molecular modeling and signaling studies revealed that the PAC1Null and PAC1Hop receptor variants can associate with β-arrestin differentially, resulting in enhanced receptor internalization and ERK activation for the PAC1Hop variant. The study amplifies our understandings of GPCR intracellular loop structure/function relationships with the first example of how the duration of endosomal ERK activation can be guided by ICL3. The results provide a framework for how changes in GPCR variant expression can impact developmental and homeostatic processes and may be contributory to maladaptive neuroplasticity underlying chronic pain and stress-related disorders.

Chronic pain syndrome is a heterogeneous group of diseases characterized by several pathological mechanisms. One in five adults in Europe may experience chronic pain. In addition to the individual burden, chronic pain has a significant societal impact because of work and school absences, loss of work, early retirement, and high social and healthcare costs. Several anti-inflammatory treatments are available for patients with inflammatory or autoimmune diseases to control their symptoms, including pain. However, patients with degenerative chronic pain conditions, some with 10-fold or more elevated incidence relative to these manageable diseases, have few long-term pharmacological treatment options, limited mainly to non-steroidal anti-inflammatory drugs or opioids. For this review, we performed multiple PubMed searches using keywords such as "pain," "neurogenic inflammation," "NGF," "substance P," "nociception," "BDNF," "inflammation," "CGRP," "osteoarthritis," and "migraine." Many treatments, most with limited scientific evidence of efficacy, are available for the management of chronic pain through a trial-and-error approach. Although basic science and pre-clinical pain research have elucidated many biomolecular mechanisms of pain and identified promising novel targets, little of this work has translated into better clinical management of these conditions. This state-of-the-art review summarizes concepts of chronic pain syndromes and describes potential novel treatment strategies.

Nowadays, the success of spinal cord stimulation (SCS) is evaluated separately in patients who have previous experiences with standard SCS and in SCS-naïve patients. Nevertheless, it is yet to be evaluated whether both patient groups are effectively distinct patient groups. Therefore, the aims of this study are twofold: 1) Are there clusters in the data to distinguish between both patient groups? 2) Can we discriminate both patient groups based on routinely collected clinical parameters?