Accepted

Migraine affects ∼15% of the adult population, and the standard treatment includes the use of triptans, ergotamines, and analgesics. Recently, CGRP and its receptor, the CLR/RAMP1 receptor complex, have been targeted for migraine treatment due to their critical roles in mediating migraine headaches. The effort has led to the approval of several anti-CGRP antibodies for chronic migraine treatment. However, many patients still suffer continuous struggles with migraine, perhaps due to the limited ability of anti-CGRP therapeutics to fully reduce CGRP levels or reach target cells. An alternative anti-CGRP strategy may help address the medical need of patients who do not respond to existing therapeutics. By serendipity, we have recently found that several chimeric adrenomedullin/adrenomedullin 2 peptides are potent CLR/RAMP receptor antagonists and self-assemble to form liquid gels. Among these analogs, the ADE651 analog, which potently inhibits CLR/RAMP1 receptor signaling, forms gels at a 6-20% level. Screening of ADE651 variants indicated that residues at the junctional region of this chimeric peptide are important for gaining the gel-forming capability. Gel-formation significantly slowed the passage of ADE651 molecules through Centricon filters. Consistently, subcutaneous injection of ADE651 gel in rats led to the sustained presence of ADE651 in circulation for >1 week. In addition, analysis of vascular blood flow in rat hindlimbs showed ADE651 significantly reduces CGRP-induced vasodilation. Because gel-forming antagonists could have direct and sustained access to target cells, ADE651 and related antagonists for CLR/RAMP receptors may represent promising candidates for targeting CGRP- and/or adrenomedullin-mediated headaches in migraine patients.

Adenomyosis is an estrogen-dependent gynecological disease. The pathogenesis of chronic pain, the main clinical symptom of adenomyosis, remains undefined. As a combination lymphocyte with both T-cell and natural killer (NK)-cell properties, NK T (NKT) cells play a role in immune defense against numerous diseases and modulate cell differentiation.

Comorbid chronic pain and post-traumatic stress disorder (PTSD) complicate the treatment of both conditions. Previous research has identified pain catastrophizing as a potentially important variable contributing to the relationship between chronic pain and PTSD. However, little is known regarding how the different dimensions of pain catastrophizing-rumination, magnification, and helplessness-uniquely contribute to the relationship between PTSD symptomatology and measures of pain outcome.

Chronic low back pain (CLBP) is a very common problem throughout the world. One treatment possibility is the multidisciplinary programme (MP) in a rehabilitation centre, which provides intensive rehabilitation through physical exercise to quickly improve the patient conditions. Patients nevertheless do not always continue the exercises when they return home. This study thus evaluated compliance with a personalised home-based programme for CLBP patients post-MP.

To quantitatively summarize the specific changes in brain structure and function in migraine patients.

Central sensitization refers to the increased responsiveness of nociceptive neurons in the central nervous system after repeated or sustained peripheral nociceptor activation. It is hypothesized to play a key role in the development of chronic pain. A hallmark of central sensitization is an increased sensitivity to noxious mechanical stimuli extending beyond the injured location, known as secondary hyperalgesia. For its ability to modulate the transmission and the processing of nociceptive inputs, attention could constitute a promising target to prevent central sensitization and the development of chronic pain. It was recently shown that the experimental induction of central sensitization at both forearms of healthy volunteers using bilateral high-frequency electrocutaneous stimulation (HFS), can be modulated by encouraging participants to selectively focus their attention to one arm, to the detriment of the other arm, resulting in a greater secondary hyperalgesia on the attended arm as compared to the unattended one. Given the potential value of the question being addressed, we conducted a preregistered replication study in a well-powered independent sample to assess the robustness of the effect, i.e., the modulatory role of spatial attention on the induction of central sensitization. This hypothesis was tested using a double-blind, within-subject design. Sixty-seven healthy volunteers performed a task that required focusing attention toward one forearm to discriminate innocuous vibrotactile stimuli while HFS was applied on both forearms simultaneously. Our results showed a significant increase in mechanical sensitivity directly and 20 min after HFS. However, in contrast to the previous study, we did not find a significant difference in the development of secondary hyperalgesia between the attended vs. unattended arms. Our results question whether spatial selective attention affects the development of secondary hyperalgesia. Alternatively, the non-replication could be because the bottom-up capture of attention caused by the HFS-mediated sensation was too strong in comparison to the top-down modulation exerted by the attentional task. In other words, the task was not engaging enough and the HFS pulses, including those on the unattended arm, were too salient to allow a selective focus on one arm and modulate nociceptive processing.

This study aimed to determine the prevalence of chronic pain and its risk factors in patients with obstructive sleep apnea (OSA).