Human Studies

Calcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraine. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and might thus possess disease modifying potential. This study addresses this question by investigating the nociceptive blink reflex (nBR), which is closely tied to central disease activity, before and after treatment with CGRP antibodies.

This study investigated the prevalence of long-term musculoskeletal post-COVID pain and their risk factors in a large cohort of COVID-19 survivors. A multicenter cohort study including patients hospitalised due to COVID-19 in five hospitals of Madrid (Spain) during the first wave of the pandemic was conducted. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview after hospital discharge for collecting data about the musculoskeletal post-COVID pain. Anxiety/depressive levels and sleep quality were likewise assessed. From 2,000 patients recruited, a total of 1,969 (46.4% women, age: 61, SD: 16 years) were assessed on average at 8.4 (SD 1.5) months after discharge. At the time of the study, 887 (45% women) reported musculoskeletal post-COVID pain. According to the presence of previous pain symptoms, the prevalence of "de novo" (new-onset) musculoskeletal post-COVID pain was 74.9%, whereas 25.1% experienced an increase of previous symptoms (exacerbated COVID-related pain). Female gender (OR1.349, 95%CI 1.059-1.720), previous history of musculoskeletal pain (OR1.553, 95%CI 1.271-1.898), the presence of myalgia (OR1.546, 95%CI 1.155-2.070) and headache (1.866, 95%CI 1.349-2.580) as COVID-19 associated onset symptoms, and days at hospital (OR1.013, 95%CI 1.004-1.022) were risk factors associated musculoskeletal post-COVID pain. In conclusion, musculoskeletal post-COVID pain is present in 45.1% of COVID-19 survivors at eight months after hospital discharge with most patients developing "de novo" post-COVID pain. Female gender, history of musculoskeletal pain, presence of myalgias and headache as COVID-19 symptoms at the acute phase, and days at hospital were risk factors associated with musculoskeletal post-COVID pain.

Painful chemotherapy induced peripheral neuropathy (CIPN) is a common complication of chemotherapy with drugs such as taxanes and platinum compounds. Currently, no methods are available for early detection of sensory changes that are associated with painful CIPN, nor are there biomarkers that are specific to painful CIPN. This study aimed to compare Diode Laser fiber type-selective stimulator (DLss), a method to selectively stimulate cutaneous C and Aδ fibers, to traditional quantitative sensory testing (QST) in determining psychophysical differences between patients with painful CIPN and a control group. Sensory testing was performed on the dorsal mid-foot of 20 patients with painful neuropathy after taxane- or platinum-based chemotherapy, and 20 patients who received similar neurotoxic chemotherapy, without painful CIPN. In a multivariable analysis, C-fiber to Aδ fiber detection threshold ratio, measured by DLss, was significantly different between the groups (p<0.05). While QST parameters such as warmth detection threshold were different between the groups in univariate analyses, these findings were likely attributable to group differences in patient age and cumulative chemotherapy dose. PERSPECTIVE: In this study, fiber-specific DLss test showed potential in identifying sensory changes that are specific for painful neuropathy, encouraging future testing of this approach as a biomarker for early detection of painful CIPN. TRIAL REGISTRATION: The study was approved by the Washington University Institutional Review Board (#201807162) and registered at ClinicalTrials.gov (NCT03687970).

Chronic low back pain is one of the most common, costly, and debilitating pain conditions worldwide. Increased mechanistic understanding of the transition from acute to chronic low back and identification of predictive biomarkers could enhance the clinical assessment performed by healthcare providers and enable the development of targeted treatment to prevent and/or better manage chronic low back pain. This study protocol was designed to identify the neurological and transcriptomic biomarkers predictive of chronic low back pain at low back pain onset. This is a prospective descriptive longitudinal inception cohort study that will follow 340 individuals with acute low back pain and 40 healthy controls over 2 years. To analyze the neurophysiological and transcriptomic biomarkers of low back pain, the protocol includes psychological and pain-related survey data that will be collected beginning within 6 weeks of low back pain onset (baseline, 6, 12, 24, 52 weeks, and 2 years) and remotely at five additional time points (8, 10, 16, 20 weeks, and 18 months). Quantitative sensory testing and collection of blood samples for RNA sequencing will occur during the six in-person visits. The study results will describe variations in the neurophysiological and transcriptomic profiles of healthy pain-free controls and individuals with low back pain who either recover to pain-free status or develop chronic low back pain.