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Rapid Improvement of Itch Associated With Atopic Dermatitis With Abrocitinib Is Partially Independent of Overall Disease Improvement: Results From Pooled Phase 2b and 3 Monotherapy Studies.

Itch, the most bothersome symptom in atopic dermatitis, is largely mediated by pruritogenic cytokines via Janus kinase 1 signaling in cutaneous sensory neurons.

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Methadone maintenance patients lack analgesic response to a cumulative intravenous dose of 32 mg of hydromorphone.

Acute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST).

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Validation of the General Health Questionnaire 12 for assessing psychological distress in patients with chronic low back pain.

The General Health Questionnaire 12 (GHQ-12) is a short easy-to-use scale to assess psychological distress. The GHQ-12 has not been validated for assessing psychological distress in patients with chronic low back pain (LBP).

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Centromedian-Parafascicular and Somatosensory Thalamic Deep Brain Stimulation for Treatment of Chronic Neuropathic Pain: A Contemporary Series of 40 Patients.

The treatment of neuropathic and central pain still remains a major challenge. Thalamic deep brain stimulation (DBS) involving various target structures is a therapeutic option which has received increased re-interest. Beneficial results have been reported in several more recent smaller studies, however, there is a lack of prospective studies on larger series providing long term outcomes. Forty patients with refractory neuropathic and central pain syndromes underwent stereotactic bifocal implantation of DBS electrodes in the centromedian-parafascicular (CM-Pf) and the ventroposterolateral (VPL) or ventroposteromedial (VPM) nucleus contralateral to the side of pain. Electrodes were externalized for test stimulation for several days. Outcome was assessed with five specific VAS pain scores (maximum, minimum, average pain, pain at presentation, allodynia). The mean age at surgery was 53.5 years, and the mean duration of pain was 8.2 years. During test stimulation significant reductions of all five pain scores was achieved with either CM-Pf or VPL/VPM stimulation. Pacemakers were implanted in 33/40 patients for chronic stimulation for whom a mean follow-up of 62.8 months (range 3-180 months) was available. Of these, 18 patients had a follow-up beyond four years. Hardware related complications requiring secondary surgeries occurred in 11/33 patients. The VAS maximum pain score was improved by ≥50% in 8/18, and by ≥30% in 11/18 on long term follow-up beyond four years, and the VAS average pain score by ≥50% in 10/18, and by ≥30% in 16/18. On a group level, changes in pain scores remained statistically significant over time, however, there was no difference when comparing the efficacy of CM-Pf versus VPL/VPM stimulation. The best results were achieved in patients with facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury, while patients with thalamic lesions had the least benefit. Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory pain.

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Slowing in peak-alpha frequency recorded after experimentally-induced muscle pain is not significantly different between high and low pain-sensitive subjects.

Peak alpha frequency (PAF) reduces during cutaneous pain, but no studies have investigated PAF during movement-related muscle pain. Whether high-pain sensitive (HPS) individuals exhibit a more pronounced PAF response to pain than low-pain sensitive (LPS) individuals is unclear. As a pain model, twenty-four participants received nerve growth factor injections into a wrist extensor muscle at Day0, Day2, and Day4. At Day4, a subgroup of twelve participants also undertook eccentric wrist exercise to induce additional pain. Pain numerical rating scale (NRS) scores and electroencephalography were recorded at Day0 (before injection), Day4, and Day6 for 3 minutes (eyes closed) with wrist at rest (Resting-state) and extension (Contraction-state). The average pain NRS scores in contraction-state across Days were used to divide participants into HPS (NRS-scores≥2) and LPS groups. PAF was calculated by frequency decomposition of electroencephalographic recordings. Compared with Day0, contraction NRS-scores only increased in HPS-group at Day4 and Day6 (P<0.001). PAF in Contraction-state decreased in both groups at Day6 compared with Day0 (P=0.011). Across days, HPS-group showed faster PAF than LPS-group during Resting-state and Contraction-state (P<0.04). Average pain NRS-scores across days during Contraction-states correlated with PAF at Day0 (P=0.012). Pain NRS-scores were associated with PAF during Contraction-state at Day4 and Day6 (P<0.05). Perspective: PAF was slowed during long-lasting movement-related pain in both groups, suggesting a widespread change in cortical excitability independent of the pain sensitivity. Moreover, HPS individuals showed faster PAF than LPS individuals during muscle pain, which may reflect a different cognitive, emotional, or attentional response to muscle pain among individuals.

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Increased GABA+ in people with migraine, headache and pain conditions- a potential marker of pain.

Treatment outcomes for migraine and other chronic headache and pain conditions typically demonstrate modest results. A greater understanding of underlying pain mechanisms may better inform treatments and improve outcomes. Increased GABA+ has been identified in recent studies of migraine, however, it is unclear if this is present in other headache and pain conditions. We primarily investigated GABA+ levels in the posterior cingulate gyrus (PCG) of people with migraine, whiplash-headache and low back pain compared to age- and sex-matched controls, GABA+ levels in the anterior cingulate cortex (ACC) and thalamus formed secondary aims. Using a cross-sectional design, we studied people with migraine, whiplash-headache or low back pain (n=56) and compared them with a pool of age-and sex-matched controls (n=22). We used spectral-edited magnetic resonance spectroscopy at 3T (MEGA-PRESS) to determine levels of GABA+ in the PCG, ACC and thalamus. PCG GABA+ levels were significantly higher in people with migraine and low back pain compared with controls (e.g. migraine 4.89 IU ± 0.62 versus controls 4.62 IU ± 0.38; p=0.02). Higher GABA+ levels in the PCG were not unique to migraine and could reflect a mechanism of chronic pain in general. A better understanding of pain at a neurochemical level informs the development of treatments that target aberrant brain neurochemistry to improve patient outcomes. PERSPECTIVE: This study provides insights into the underlying mechanisms of chronic pain. Higher levels of GABA+ in the PCG may reflect an underlying mechanism of chronic headache and pain conditions. This knowledge may help improve patient outcomes through developing treatments that specifically address this aberrant brain neurochemistry.

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Chronic pain and COVID-19: The association of delay discounting with perceived stress and pain severity.

The coronavirus disease pandemic of 2019 (COVID-19) is a worldwide threat to public health that has significantly affected the United States. The pandemic poses a variety of health risks including stressful disruptions in social and economic activity. Understanding the pandemic's effects on already vulnerable populations, such as individuals with chronic pain, may inform healthcare preparation for future catastrophic events. Given the association between excessive discounting of delayed rewards and chronic pain, this study examined relationships between delay discounting, pain severity, and COVID-19 perceived stress in individuals with chronic pain. Individuals reporting chronic pain (N = 180; 41% female; 86% white; 59% with a college degree) were recruited via the Amazon Mechanical Turk platform in this cross-sectional study. Measures of pain severity, delay discounting, probability discounting, and COVID-19 perceived stress were collected. Delay discounting was a significant predictor of overall pain severity (p < .02) and COVID-19 perceived stress (p < .001). Also, the magnitude of COVID-19 perceived stress fully mediated the relationship between delay discounting and overall pain severity (p = .004). Probability discounting was not a significant predictor of pain severity or COVID-19 perceived stress (p > .05). These findings highlight the importance of excessive discounting of delayed rewards as a potential determinant of pain severity as well as predictor of perceived stress related to the COVID-19 pandemic. Thus, the discounting of delayed rewards is of particular therapeutic importance for individuals with chronic pain in the context of stressful events. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective observational study.

Pain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA.

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Intracortical human recordings reveal intensity coding for the pain of others in the insula.

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Differences in Frontal Lobe Dysfunction in Patients with Episodic and Chronic Migraine.

Neuroimaging and neuropsychological investigations have indicated that migraineurs exhibit frontal lobe-related cognitive impairment. We investigated whether orbitofrontal and dorsolateral functioning differed between individuals with episodic migraine (EM) and chronic migraine (CM), focusing on orbitofrontal dysfunction because it is implicated in migraine chronification and medication overuse headache (MOH) in migraineurs. This cross-sectional study recruited women with CM with/without MOH (CM + MOH, CM – MOH), EM, and control participants who were matched in terms of age and education. We conducted neuropsychological assessments of frontal lobe function via the Trail Making Test (TMT) A and B, the Wisconsin Card Sorting Test (WCST), and the Iowa Gambling Task (IGT). We enrolled 36 CM (19 CM + MOH, 17 CM – MOH), 30 EM, and 30 control participants. The CM patients performed significantly ( < 0.01) worse on the TMT A and B than the EM patients and the control participants. The WCST also revealed significant differences, with poorer performance in the CM patients versus the EM patients and the control participants. However, the net scores on the IGT did not significantly differ among the three groups. Our findings suggest that the CM patients exhibited frontal lobe dysfunction, and, particularly, dorsolateral dysfunction. However, we found no differences in frontal lobe function according to the presence or absence of MOH.

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