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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

Responses to peripheral stimulation contralateral to hindpaw ischemia.(a) Example of spinal responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic treatment applied to the right hindpaw. (b) Relative amplitudes of the responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic or sham treatment applied to the right hindpaw. Responses were normalized by those recorded before ischemic or sham treatment. (c) Example of S1 responses to left hindpaw stimulation before, during, and after ischemic treatment applied to the right hindpaw. (d) Relative amplitudes of the responses to left hindpaw stimulation.
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f5: Responses to peripheral stimulation contralateral to hindpaw ischemia.(a) Example of spinal responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic treatment applied to the right hindpaw. (b) Relative amplitudes of the responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic or sham treatment applied to the right hindpaw. Responses were normalized by those recorded before ischemic or sham treatment. (c) Example of S1 responses to left hindpaw stimulation before, during, and after ischemic treatment applied to the right hindpaw. (d) Relative amplitudes of the responses to left hindpaw stimulation.

Mentions: Changes in neural responses were not observable during ischemic treatment in the ipsilateral spinal cord or in the contralateral S1 because of conduction block of the peripheral nerves. However, we found that the spinal responses elicited by vibratory stimulation applied to the hindpaw contralateral to the ischemic treatment were significantly potentiated during ischemic treatment (Fig. 5a,b). The potentiation was maintained for at least 60 min after hindpaw ischemia. Cortical responses in S1 ipsilateral to the ischemic treatment were similarly potentiated during and after hindpaw ischemia (Fig. 5c,d), indicating that spinal and cortical potentiation had already been initiated during ischemic treatment. Comparison of the potentiation at 60 min after hindpaw ischemia in the spinal cord (ipsilateral: 138 ± 11%, n = 7; contralateral: 140 ± 6%, n = 5) and S1 (contralateral: 165 ± 18%, n = 13; ipsilateral; 171 ± 14%, n = 14) revealed that the neural changes in the contralateral spinal cord and the ipsilateral S1 were comparable to those in the opposite sides. These results suggest that reduction in the mechanical thresholds of the right hindpaw-withdrawal reflex could be observed after ischemic treatment applied to the left thigh. In accordance with these results, a slight but significant reduction in the mechanical threshold (P < 0.02) was observed in the right hindpaw withdrawal reflex at 3 h after ischemia applied to the left hindpaw. However, S1 responses to forepaw stimulation were not clearly affected by ischemia applied to the hindpaw (Supplementary Figs S4).


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)

Responses to peripheral stimulation contralateral to hindpaw ischemia.(a) Example of spinal responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic treatment applied to the right hindpaw. (b) Relative amplitudes of the responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic or sham treatment applied to the right hindpaw. Responses were normalized by those recorded before ischemic or sham treatment. (c) Example of S1 responses to left hindpaw stimulation before, during, and after ischemic treatment applied to the right hindpaw. (d) Relative amplitudes of the responses to left hindpaw stimulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Responses to peripheral stimulation contralateral to hindpaw ischemia.(a) Example of spinal responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic treatment applied to the right hindpaw. (b) Relative amplitudes of the responses to left hindpaw stimulation before, during, and at 30 min and 60 min after ischemic or sham treatment applied to the right hindpaw. Responses were normalized by those recorded before ischemic or sham treatment. (c) Example of S1 responses to left hindpaw stimulation before, during, and after ischemic treatment applied to the right hindpaw. (d) Relative amplitudes of the responses to left hindpaw stimulation.
Mentions: Changes in neural responses were not observable during ischemic treatment in the ipsilateral spinal cord or in the contralateral S1 because of conduction block of the peripheral nerves. However, we found that the spinal responses elicited by vibratory stimulation applied to the hindpaw contralateral to the ischemic treatment were significantly potentiated during ischemic treatment (Fig. 5a,b). The potentiation was maintained for at least 60 min after hindpaw ischemia. Cortical responses in S1 ipsilateral to the ischemic treatment were similarly potentiated during and after hindpaw ischemia (Fig. 5c,d), indicating that spinal and cortical potentiation had already been initiated during ischemic treatment. Comparison of the potentiation at 60 min after hindpaw ischemia in the spinal cord (ipsilateral: 138 ± 11%, n = 7; contralateral: 140 ± 6%, n = 5) and S1 (contralateral: 165 ± 18%, n = 13; ipsilateral; 171 ± 14%, n = 14) revealed that the neural changes in the contralateral spinal cord and the ipsilateral S1 were comparable to those in the opposite sides. These results suggest that reduction in the mechanical thresholds of the right hindpaw-withdrawal reflex could be observed after ischemic treatment applied to the left thigh. In accordance with these results, a slight but significant reduction in the mechanical threshold (P < 0.02) was observed in the right hindpaw withdrawal reflex at 3 h after ischemia applied to the left hindpaw. However, S1 responses to forepaw stimulation were not clearly affected by ischemia applied to the hindpaw (Supplementary Figs S4).

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