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To determine whether erenumab is effective and safe in refractory chronic migraine with medication overuse headache.
Learn More >The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to non-surgical treatments. Participants with chronic axial low back pain were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60 days, after which the leads were removed. Participants were followed long-term for 12 months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (Primary Endpoint) and 6 months after lead removal (8 months after start of treatment), with some participant follow-up visits thereafter in progress. Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-three percent of participants were successes for the Primary Endpoint, reporting clinically significant (≥30%) reductions in back pain intensity after the 2-month percutaneous PNS treatment (n=54/74). While prospective follow up is ongoing, among those who had already completed the long-term follow up visits (n=51), reductions in pain intensity, disability, and pain interference were sustained in a majority of participants through 14 months after the start of treatment. Given the minimally invasive, non-destructive nature of percutaneous PNS and the significant benefits experienced by participants who were recalcitrant to non-surgical treatments, percutaneous PNS may provide a promising first-line neurostimulation treatment option for patients with chronic axial back pain.
Learn More >Moderate to severe pain is often treated with opioids, but central mechanisms underlying opioid analgesia are poorly understood. Findings thus far have been contradictory and none could infer opioid specific effects. This placebo-controlled, randomized, two-way cross-over, double-blinded study aimed to explore opioid specific effects on central processing of external stimuli. Twenty healthy male volunteers were included and three sets of assessments were done at each of the two visits: 1) baseline, 2) during continuous morphine or placebo intravenous infusion and 3) during simultaneous morphine + naloxone or placebo infusion. Opioid antagonist naloxone was introduced in order to investigate opioid specific effects by observing which morphine effects are reversed by this intervention. Quantitative sensory testing (QST), spinal nociceptive withdrawal reflexes (NWR), spinal electroencephalography (EEG), cortical EEG responses to external stimuli and resting EEG were measured and analyzed. Longer lasting pain (cold-pressor test – hand in 2° water for two minutes, tetanic electrical), deeper structure pain (bone pressure) and strong nociceptive (NWR) stimulations were the most sensitive QST measures of opioid analgesia. In line with this, the principal opioid specific central changes were seen in NWRs, EEG responses to NWRs and cold-pressor EEG. The magnitude of NWRs together with amplitudes and insular source strengths of the corresponding EEG responses were attenuated. The decreases in EEG activity were correlated to subjective unpleasantness scores. Brain activity underlying slow cold-pressor EEG (1-4Hz) was decreased, whereas the brain activity underlying faster EEG (8-12Hz) was increased. These changes were strongly correlated to subjective pain relief. This study points to evidence of opioid specific effects on perception of external stimuli and the underlying central responses. The analgesic response to opioids is likely a synergy of opioids acting at both spinal and supra-spinal levels of the central nervous system. Due to the strong correlations with pain relief, the changes in EEG signals during cold-pressor test have the potential to serve as biomarkers of opioid analgesia. Perspective: This exploratory study presents evidence of opioid specific effects on the pain system at peripheral and central levels. The findings give insights into which measures are the most sensitive for assessing opioid-specific effects.
Learn More >Patient Reported Outcomes (PROs) are utilized in clinical registries and trials, necessitating development of benchmarks to enhance interpretability. This study aimed to 1) examine if PROMIS measures administered via computer adaptive testing (CAT) were responsive to change, and 2) highlight one method of assessing clinically significant change for youth seen in a tertiary pain clinic. Clinically significant change was achieved if patients had significantly reliable pre-to-post-changes greater than Reliable Change Index (RCI) value and reported decreased symptoms by at least one severity level (e.g., moderate to mild). Participants were 328 youth (8-17 years old) seen in a tertiary pediatric pain management clinic. Small to moderate effect sizes were noted across PROMIS measures (except Peer Relations). Reliable magnitudes of change were estimated for this sample as approximately 6-point reduction for Pain Interference and Mobility, 9 for Fatigue, and 11 for Anxiety and Depression. Depending on the measure, 10-24% were categorized as improved, 3-6% as deteriorated, and 68-81% were either not clinically elevated at baseline or remained unchanged at 3-months. Overall, PROMIS CAT measures demonstrated responsiveness to change over time. Estimation of clinically significant change offers preliminary yet rigorous benchmarks for evaluating treatment response and sets the stage for understanding treatment effects. Perspective This study assesses responsiveness of CAT administered PROMIS measures and highlights one methodological approach of presenting clinical significance for assessing treatment outcomes in pediatric chronic pain. These benchmarks will allow clinicians and researchers to evaluate treatment response utilizing PROs while allowing for a deeper understanding of treatment effects.
Learn More >Chronic low back pain (CLBP) is a global health problem associated with an increasing burden on individuals, health care systems, and society. Common treatments for people with CLBP produce, on average, small short-term improvements in pain and function compared with minimal care. The RESOLVE trial randomly allocated 276 people with CLBP to a new complex treatment strategy, pain education integrated with graded sensorimotor precision training (RESOLVE), or a sham control. The RESOLVE treatment was developed within a theoretical framework to target possible treatment mechanisms associated with CLBP development and persistence.
Learn More >Knowledge of etiological mechanisms underlying whiplash-associated disorders (WAD) is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in WAD would facilitate diagnosis, strengthen patients' subjective pain reports and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study we evaluated combined [11C]D-deprenyl positron emission tomography and computed tomography (PET-CT)) after acute whiplash injury and at 6 month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]D-deprenyl PET-CT, subjective pain levels, self-rated neck disability and active cervical range of motion were recorded within seven days after injury, and again at six month follow up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow up, some patients had recovered, and some showed persistent symptoms, and reductions in [11C]D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that PET/CT detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.
Learn More >Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that placebo effects on pain generalize to other sensations and that nocebo effects generalize within itch modalities. However, it has not yet been investigated whether learned effects can generalize within pain stimulus modalities or from pain to itch. Our aims were to test whether placebo and nocebo effects can generalize within pain modalities, i.e., from heat pain to pressure pain, and across somatosensory sensations with psychophysiological similarities, i.e., from heat pain to cowhage-evoked itch. For this purpose, sixty-five healthy participants were randomized to either a placebo or nocebo group. All participants firstly underwent a conditioning and verbal suggestion procedure with heat pain stimuli. Subsequently, responses to heat pain, pressure pain, and cowhage-evoked itch stimuli were tested. Results showed that altered levels of heat and pressure pain with the conditioned cue in both placebo and nocebo groups in the expected directions, but no significant difference in itch in both groups. In conclusion, placebo and nocebo effects on pain may generalize within but not across stimulus modalities. This study provides a novel perspective on the role that response generalization plays in physical symptoms.
Learn More >Yoga is a meditative movement therapy focused on mind-body awareness. The impact of yoga on health-related quality of life (HRQOL) outcomes in patients with chemotherapy-induced peripheral neuropathy (CIPN) is unclear.
Learn More >Central sensitization is a condition that represents a cascade of neurological adaptations, resulting in an amplification of nociceptive responses from noxious and non-noxious stimuli. However, whether this abnormality translates into motor output and more specifically, ventral horn abnormalities, needs to be further explored. Twenty healthy participants aged 20-70 were randomly allocated to topical capsaicin or a placebo topical cream which was applied onto their left upper back to induce a transient state of sensitization. Visual analogue scale (VAS) ratings of pain intensity and brush allodynia score (BAS) were used to determine the presence of pain and secondary allodynia. Surface electromyography (sEMG) and intramuscular electromyography (iEMG) were used to record motor unit activity from the upper trapezius and infraspinatus muscles before and twenty minutes after application of capsaicin/placebo. Motor unit recruitment and variability were analyzed in the sEMG and iEMG, respectively. An independent t-test and Kruskal-Wallis H test were performed on the data. The sEMG results demonstrated a shift in the motor unit recruitment pattern in the upper trapezius muscle, while the iEMG showed a change in motor unit variability after application of capsaicin. These results suggest that capsaicin-induced central sensitization may cause changes in ventral horn excitability outside of the targeted spinal cord segment, affecting efferent pathway outputs. This preclinical evidence may provide some explanation for the influence of central sensitization on changes in movement patterns that occur in patients who have pain encouraging of further clinical investigation.Clinical Trials registration number: NCT04361149; date of registration: 24-Apr-2020.
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