Pharmacological Functional MRI Assessment of the Effect of Ibuprofen-Arginine in Painful Conditions

Abstract

Pharmacological functional magnetic resonance imaging (phMRI) is a valuable tool for the investigation of pharmacological effects of a drug on pain processing. We hypothesized that the ibuprofen-arginine combination, in line with its characterlstlc analgesic properties, may influence the phMRI response at the central level, as compared to placebo. Ten healthy subjects underwent a double-blind, placebo-controlled, randomized, cross-over phFMRI study with somatosensory painful stimulation of the right median nerve. We measured the blood oxygen level dependent (BOLD) signal variations induced in conditions of pain after oral administration of either ibuprofen-arginine or placebo formulations. Independent component analysis (leA) was used for the analysis of the tMRI data, without assuming a specific hemodynamic response function (HRF), which may be altered by drug administration. Median nerve electrical painful stimulation mainly activated the primary contralateral and the secondary somatosensory cortices, the insula, the supplementary motor area, and the middle frontal gyrus. Placebo and ibuprofen-arginine administration induced activation bilaterally in the premotor cortex, and an overall reduction in the other pain-related areas, which was more prominent in the left hemisphere. A task-related increase of BOLD signal between drug and placebo was observed bilaterally in the primary somatosensory area and the middle frontal gyrus without any changes in subjective pain scores. Overall, our findings show that ibuprofen-arginine, in line with the characteristic analgesic properties of ibuprofen, influences the BOLD response in specific pain-related brain areas with respect to placebo, with a vasoactive effect possibly due to arginine.Pharmacological functional magnetic resonance imaging (phFMRI) is a functional neuroimaging modality that combines the administration of a given dose of a drug with the imaging of brain activity through the blood oxygen level dependent (BOLD) technique. phFMRI permits to investigate in vivo and non-invasively the direct effects of the drug on hemodynamic response according to an on/off paradigm, or the drug-induced modulation on specific functional networks activated by physiologically controlled stimuli (1). Neuronal activation, as a consequence of stimulation, locally

Correlation of Pain Reduction with fMRI BOLD Response in Osteoarthritis Patients Treated with Paracetamol: Randomized, Double-Blind, Crossover Clinical Efficacy Study

“…In clinical studies in patients with OA, painful mechanical stimulation of the affected knee joint has been associated with blood oxygen level–dependent (BOLD) responses measured by fMRI in the brain regions commonly involved in acute pain [ 4 , 6 , 10 ]. In pharmacologic investigations in healthy volunteers, analgesics such as ibuprofen-arginine, remifentanil, nalbuphine, naloxone, and naproxen have shown greater fMRI BOLD responses in pain-related brain regions compared with placebo [ 11–15 ]. One fMRI study in healthy volunteers receiving painful stimulation showed that APAP treatment was associated with reduced activation in the insula, anterior cingulate cortex, thalamus, and prefrontal cortices compared with placebo [ 16 ].…”

Effect of Ibuprofen on BrainAGE: A Randomized, Placebo-Controlled, Dose-Response Exploratory Study

“…In the first study, 10 healthy participants underwent a double-blind, placebo-controlled, randomized, crossover pharmacological functional magnetic resonance imaging (MRI) study during somatosensory painful stimulation of the right median nerve. The study suggested that ibuprofen acutely attenuated the blood oxygen level–dependent response in specific pain-related brain areas (20). In a recent study, only gabapentin but not ibuprofen (600-mg single dose) suppressed the resting-state functional connectivity during central sensitization between the thalamus and secondary somatosensory cortex (21).…”

Cholesterol: An Inflammatory Compound

“…Human plaque analysis has revealed that MMP-9 is catalytically active and may thus contribute to the dysregulation of extracellular matrix that leads to plaque rupture during the complication of atherothrombosis (23)(24)(25)(26). Further evidence suggests that local overexpression of MMP-9 promotes intravascular thrombus formation through increased tissue factor expression and tissue factor-mediated activation of the coagulation cascade (27)(28)(29)(30) These data support an important role for MMP-9 in several stages of atherosclerosis.…”