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Spinal mechanisms underlying potentiation of hindpaw responses observed after transient hindpaw ischemia in mice.

Watanabe T, Sasaki M, Komagata S, Tsukano H, Hishida R, Kohno T, Baba H, Shibuki K - Sci Rep (2015)

Bottom Line: The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors.Potentiation already appeared during ischemic treatment for 30 min.The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Neurophysiology, Brain Research Institute, Niigata University,1-757 Asahi-machi, Chuo-ku, Niigata 951-8585, Japan [2] Department of Anesthesiology, School of Medicine, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8510, Japan.

ABSTRACT
Transient ischemia produces postischemic tingling sensation. Ischemia also produces nerve conduction block that may modulate spinal neural circuits. In the present study, reduced mechanical thresholds for hindpaw-withdrawal reflex were found in mice after transient hindpaw ischemia, which was produced by a high pressure applied around the hindpaw for 30 min. The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors. Neural activities in the spinal cord and the primary somatosensory cortex (S1) were investigated using activity-dependent changes in endogenous fluorescence derived from mitochondrial flavoproteins. Ischemic treatment induced potentiation of the ipsilateral spinal and contralateral S1 responses to hindpaw stimulation. Both types of potentiation were blocked by spinal application of LY354740. The contralateral S1 responses, abolished by lesioning the ipsilateral dorsal column, reappeared after ischemic treatment, indicating that postischemic tingling sensation reflects a sensory modality shift from tactile sensation to nociception in the spinal cord. Changes in neural responses were investigated during ischemic treatment in the contralateral spinal cord and the ipsilateral S1. Potentiation already appeared during ischemic treatment for 30 min. The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

No MeSH data available.


Related in: MedlinePlus

Potentiation of the spinal responses after hindpaw ischemia.(a) Example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T13 and L1 level (upper panels). The left-most panels are original fluorescence images, and others are pseudocolor images of response magnitudes in ΔF/F0 recorded at the time before and after the stimulus onset shown on each image. Another example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T12 and T13 level (lower panels). (b) Example of spinal responses recorded in the same mouse before, during, and 30–120 min after ischemic treatment applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 100 × 25 pixels shown in the second panel. (c) Relative amplitudes of spinal responses during and after ischemic treatment. The amplitudes were normalized by those recorded before hindpaw ischemia. (d) Example of spinal responses recorded before and at 60 min after sham treatment. (e) Example of spinal responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (f) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, or hindpaw ischemia with spinal application of 10 nM LY354740.
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f2: Potentiation of the spinal responses after hindpaw ischemia.(a) Example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T13 and L1 level (upper panels). The left-most panels are original fluorescence images, and others are pseudocolor images of response magnitudes in ΔF/F0 recorded at the time before and after the stimulus onset shown on each image. Another example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T12 and T13 level (lower panels). (b) Example of spinal responses recorded in the same mouse before, during, and 30–120 min after ischemic treatment applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 100 × 25 pixels shown in the second panel. (c) Relative amplitudes of spinal responses during and after ischemic treatment. The amplitudes were normalized by those recorded before hindpaw ischemia. (d) Example of spinal responses recorded before and at 60 min after sham treatment. (e) Example of spinal responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (f) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, or hindpaw ischemia with spinal application of 10 nM LY354740.

Mentions: Because the behavioral test data suggested the presence of some spinal plasticity, we recorded ipsilateral spinal responses elicited by vibratory hindpaw stimulation using flavoprotein fluorescence imaging. Hindpaw stimulation produced an increase in fluorescence on the dorsal surface of the ipsilateral spinal cord corresponding to the dorsal horn at the T13 and L1 level (Fig. 2a). Because minimal response was found at T12, the fluorescence changes were attributed mainly to localized activities in the dorsal horn but not to ascending afferent activities mediated via the dorsal column. The responses started at 0.2 s after the onset of the stimulation, and peaked at approximately 1% in ΔF/F0 at 0.6–0.8 s after the stimulus onset. Although these properties were similar to those recorded in cortical areas726, the decay was slower than that of the cortical responses, as the hemodynamic responses were not marked in the spinal cord (Supplementary Figs S2).


Spinal mechanisms underlying potentiation of hindpaw responses observed after transient hindpaw ischemia in mice.

Watanabe T, Sasaki M, Komagata S, Tsukano H, Hishida R, Kohno T, Baba H, Shibuki K - Sci Rep (2015)

Potentiation of the spinal responses after hindpaw ischemia.(a) Example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T13 and L1 level (upper panels). The left-most panels are original fluorescence images, and others are pseudocolor images of response magnitudes in ΔF/F0 recorded at the time before and after the stimulus onset shown on each image. Another example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T12 and T13 level (lower panels). (b) Example of spinal responses recorded in the same mouse before, during, and 30–120 min after ischemic treatment applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 100 × 25 pixels shown in the second panel. (c) Relative amplitudes of spinal responses during and after ischemic treatment. The amplitudes were normalized by those recorded before hindpaw ischemia. (d) Example of spinal responses recorded before and at 60 min after sham treatment. (e) Example of spinal responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (f) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, or hindpaw ischemia with spinal application of 10 nM LY354740.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499883&req=5

f2: Potentiation of the spinal responses after hindpaw ischemia.(a) Example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T13 and L1 level (upper panels). The left-most panels are original fluorescence images, and others are pseudocolor images of response magnitudes in ΔF/F0 recorded at the time before and after the stimulus onset shown on each image. Another example of ipsilateral spinal responses elicited by vibratory stimulation applied to the left hindpaw at T12 and T13 level (lower panels). (b) Example of spinal responses recorded in the same mouse before, during, and 30–120 min after ischemic treatment applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 100 × 25 pixels shown in the second panel. (c) Relative amplitudes of spinal responses during and after ischemic treatment. The amplitudes were normalized by those recorded before hindpaw ischemia. (d) Example of spinal responses recorded before and at 60 min after sham treatment. (e) Example of spinal responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (f) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, or hindpaw ischemia with spinal application of 10 nM LY354740.
Mentions: Because the behavioral test data suggested the presence of some spinal plasticity, we recorded ipsilateral spinal responses elicited by vibratory hindpaw stimulation using flavoprotein fluorescence imaging. Hindpaw stimulation produced an increase in fluorescence on the dorsal surface of the ipsilateral spinal cord corresponding to the dorsal horn at the T13 and L1 level (Fig. 2a). Because minimal response was found at T12, the fluorescence changes were attributed mainly to localized activities in the dorsal horn but not to ascending afferent activities mediated via the dorsal column. The responses started at 0.2 s after the onset of the stimulation, and peaked at approximately 1% in ΔF/F0 at 0.6–0.8 s after the stimulus onset. Although these properties were similar to those recorded in cortical areas726, the decay was slower than that of the cortical responses, as the hemodynamic responses were not marked in the spinal cord (Supplementary Figs S2).

Bottom Line: The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors.Potentiation already appeared during ischemic treatment for 30 min.The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Neurophysiology, Brain Research Institute, Niigata University,1-757 Asahi-machi, Chuo-ku, Niigata 951-8585, Japan [2] Department of Anesthesiology, School of Medicine, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8510, Japan.

ABSTRACT
Transient ischemia produces postischemic tingling sensation. Ischemia also produces nerve conduction block that may modulate spinal neural circuits. In the present study, reduced mechanical thresholds for hindpaw-withdrawal reflex were found in mice after transient hindpaw ischemia, which was produced by a high pressure applied around the hindpaw for 30 min. The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors. Neural activities in the spinal cord and the primary somatosensory cortex (S1) were investigated using activity-dependent changes in endogenous fluorescence derived from mitochondrial flavoproteins. Ischemic treatment induced potentiation of the ipsilateral spinal and contralateral S1 responses to hindpaw stimulation. Both types of potentiation were blocked by spinal application of LY354740. The contralateral S1 responses, abolished by lesioning the ipsilateral dorsal column, reappeared after ischemic treatment, indicating that postischemic tingling sensation reflects a sensory modality shift from tactile sensation to nociception in the spinal cord. Changes in neural responses were investigated during ischemic treatment in the contralateral spinal cord and the ipsilateral S1. Potentiation already appeared during ischemic treatment for 30 min. The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

No MeSH data available.


Related in: MedlinePlus