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      Hemodynamic and Light-Scattering Changes of Rat Spinal Cord and Primary Somatosensory Cortex in Response to Innocuous and Noxious Stimuli

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          Neuroimaging technologies with an exceptional spatial resolution and noninvasiveness have become a powerful tool for assessing neural activity in both animals and humans. However, the effectiveness of neuroimaging for pain remains unclear partly because the neurovascular coupling during pain processing is not completely characterized. Our current work aims to unravel patterns of neurovascular parameters in pain processing. A novel fiber-optic method was used to acquire absolute values of regional oxy- (HbO) and deoxy-hemoglobin concentrations, oxygen saturation rates (SO 2), and the light-scattering coefficients from the spinal cord and primary somatosensory cortex (SI) in 10 rats. Brief mechanical and electrical stimuli (ranging from innocuous to noxious intensities) as well as a long-lasting noxious stimulus (formalin injection) were applied to the hindlimb under pentobarbital anesthesia. Interhemispheric comparisons in the spinal cord and SI were used to confirm functional activation during sensory processing. We found that all neurovascular parameters showed stimulation-induced changes; however, patterns of changes varied with regions and stimuli. Particularly, transient increases in HbO and SO 2 were more reliably attributed to brief stimuli, whereas a sustained decrease in SO 2 was more reliably attributed to formalin. Only the ipsilateral SI showed delayed responses to brief stimuli. In conclusion, innocuous and noxious stimuli induced significant neurovascular responses at critical centers (e.g., the spinal cord and SI) along the somatosensory pathway; however, there was no single response pattern (as measured by amplitude, duration, lateralization, decrease or increase) that was able to consistently differentiate noxious stimuli. Our results strongly suggested that the neurovascular response patterns differ between brief and long-lasting noxious stimuli, and can also differ between the spinal cord and SI. Therefore, a use of multiple-parameter strategy tailored by stimulus modality (brief or long-lasting) as well as region-dependent characteristics may be more effective in detecting pain using neuroimaging technologies.

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          Most cited references 42

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          Ethical guidelines for investigations of experimental pain in conscious animals.

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            Optical coherence tomography.

            A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.
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              The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats.

              A method for assessing pain and analgesia in rats and cats is described. The procedure involves subcutaneous injection of dilute formalin into the forepaw, after which the animal's responses are rated according to objective behavioral criteria. The formalin test is a statistically valid technique which has two advantages over other pain tests: (1) little or no restraint is necessary, permitting unhindered observation of the complete range of behavioral responses; and (2) the pain stimulus is continuous rather than transient, thus bearing greater resemblance to most clinical pain. The analgesic effects of morphine, meperidine, and stimulation of the periaqueductal grey matter are evaluated using this test.

                Author and article information

                Role: Academic Editor
                Brain Sci
                Brain Sci
                Brain Sciences
                29 September 2015
                December 2015
                : 5
                : 4
                : 400-418
                [1 ]Departments of Psychology, University of Texas at Arlington, Arlington, TX 76019, USA; E-Mail: ypeng@
                [2 ]Department of Neurological Surgery, University of California San Francisco, 1700 Owens Street, San Francisco, CA 94158, USA
                [3 ]Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA; E-Mail: hanli@
                Author notes

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: jiwei.he@ ; Tel.: +1-41-5502-7397.
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (



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