Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates

The antineoplastic agent oxaliplatin induces an acute hypersensitivity evoked by cold that has been suggested to be due to sensitized central and peripheral neurons. Rodent-based preclinical studies have suggested numerous treatments for the alleviation of oxaliplatin-induced neuropathic pain, but few have demonstrated robust clinical efficacy. One issue is that current understanding of the pathophysiology of oxaliplatin-induced neuropathic pain is primarily based on rodent models, which might not entirely recapitulate the clinical pathophysiology. In addition, there is currently no objective physiological marker for pain that could be utilized to objectively indicate treatment efficacy. Nonhuman primates are phylogenetically and neuroanatomically similar to humans; thus, disease mechanism in nonhuman primates could reflect that of clinical oxaliplatin-induced neuropathy. Cold-activated pain-related brain areas in oxaliplatin-treated macaques were attenuated with duloxetine, the only drug that has demonstrated clinical efficacy for chemotherapy-induced neuropathic pain. By contrast, drugs that have not demonstrated clinical efficacy in oxaliplatin-induced neuropathic pain did not reduce brain activation. Thus, a nonhuman primate model could greatly enhance understanding of clinical pathophysiology beyond what has been obtained with rodent models and, furthermore, brain activation could serve as an objective marker of pain and therapeutic efficacy.

Download Full-text

Lactate transporters in the rat barrel cortex sustain whisker-dependent BOLD fMRI signal and behavioral performance

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2112466118 ◽

2021 ◽

Vol 118 (47) ◽

pp. e2112466118

Author(s):

Hélène Roumes ◽

Charlotte Jollé ◽

Jordy Blanc ◽

Imad Benkhaled ◽

Carolina Piletti Chatain ◽

...

Keyword(s):

Barrel Cortex ◽

Recognition Task ◽

Brain Activation ◽

Functional Brain Imaging ◽

Cortical Activation ◽

Resonance Spectroscopy ◽

Behavioral Performance ◽

Bold Response ◽

Metabolic Cooperation ◽

Bold Fmri

Lactate is an efficient neuronal energy source, even in presence of glucose. However, the importance of lactate shuttling between astrocytes and neurons for brain activation and function remains to be established. For this purpose, metabolic and hemodynamic responses to sensory stimulation have been measured by functional magnetic resonance spectroscopy and blood oxygen level-dependent (BOLD) fMRI after down-regulation of either neuronal MCT2 or astroglial MCT4 in the rat barrel cortex. Results show that the lactate rise in the barrel cortex upon whisker stimulation is abolished when either transporter is down-regulated. Under the same paradigm, the BOLD response is prevented in all MCT2 down-regulated rats, while about half of the MCT4 down-regulated rats exhibited a loss of the BOLD response. Interestingly, MCT4 down-regulated animals showing no BOLD response were rescued by peripheral lactate infusion, while this treatment had no effect on MCT2 down-regulated rats. When animals were tested in a novel object recognition task, MCT2 down-regulated animals were impaired in the textured but not in the visual version of the task. For MCT4 down-regulated animals, while all animal succeeded in the visual task, half of them exhibited a deficit in the textured task, a similar segregation into two groups as observed for BOLD experiments. Our data demonstrate that lactate shuttling between astrocytes and neurons is essential to give rise to both neurometabolic and neurovascular couplings, which form the basis for the detection of brain activation by functional brain imaging techniques. Moreover, our results establish that this metabolic cooperation is required to sustain behavioral performance based on cortical activation.

Download Full-text

A Quantitative Comparison of Simultaneous BOLD fMRI and NIRS Recordings during Functional Brain Activation

NeuroImage ◽

10.1006/nimg.2002.1227 ◽

2002 ◽

Vol 17 (2) ◽

pp. 719-731 ◽

Cited By ~ 645

Author(s):

Gary Strangman ◽

Joseph P. Culver ◽

John H. Thompson ◽

David A. Boas

Keyword(s):

Brain Activation ◽

Quantitative Comparison ◽

Functional Brain ◽

Bold Fmri

Download Full-text

Faculty Opinions recommendation of BOLD fMRI activation for anti-saccades in nonhuman primates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1145006.602120 ◽

2009 ◽

Author(s):

Aina Puce

Keyword(s):

Nonhuman Primates ◽

Bold Fmri ◽

Anti Saccades

Download Full-text

Thermal Psychophysics and Associated Brain Activation Patterns Along a Continuum of Healthy Aging

Pain Medicine ◽

10.1093/pm/pnz281 ◽

2019 ◽

Vol 21 (9) ◽

pp. 1779-1792 ◽

Cited By ~ 1

Author(s):

Paul A Beach ◽

Ronald L Cowan ◽

Mary S Dietrich ◽

Stephen P Bruehl ◽

Sebastian W Atalla ◽

...

Keyword(s):

Older Adults ◽

Thermal Sensation ◽

Novelty Detection ◽

Brain Activation ◽

Age Effects ◽

Moderate Pain ◽

Activation Patterns ◽

Healthy Older Adults ◽

Percent Signal Change ◽

Age Related

Abstract Objective To examine psychophysical and brain activation patterns to innocuous and painful thermal stimulation along a continuum of healthy older adults. Design Single center, cross-sectional, within-subjects design. Methods Thermal perceptual psychophysics (warmth, mild, and moderate pain) were tested in 37 healthy older adults (65–97 years, median = 73 years). Percept thresholds (oC) and unpleasantness ratings (0–20 scale) were obtained and then applied during functional magnetic resonance imaging scanning. General linear modeling assessed effects of age on psychophysical results. Multiple linear regressions were used to test the main and interaction effects of brain activation against age and psychophysical reports. Specifically, differential age effects were examined by comparing percent-signal change slopes between those above/below age 73 (a median split). Results Advancing age was associated with greater thresholds for thermal perception (z = 2.09, P = 0.037), which was driven by age and warmth detection correlation (r = 0.33, P = 0.048). Greater warmth detection thresholds were associated with reduced hippocampal activation in “older” vs “younger” individuals (>/<73 years; beta < 0.40, P < 0.01). Advancing age, in general, was correlated with greater activation of the middle cingulate gyrus (beta > 0.44, P < 0.01) during mild pain. Differential age effects were found for prefrontal activation during moderate pain. In “older” individuals, higher moderate pain thresholds and greater degrees of moderate pain unpleasantness correlated with lesser prefrontal activation (anterolateral prefrontal cortex and middle–frontal operculum; beta < –0.39, P < 0.009); the opposite pattern was found in “younger” individuals. Conclusions Advancing age may lead to altered thermal sensation and (in some circumstances) altered pain perception secondary to age-related changes in attention/novelty detection and cognitive functions.

Download Full-text