Limits...
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 S1 responses after ischemic treatment.(a) Example of contralateral S1 responses elicited by vibratory stimulation applied to the left hindpaw. (b) Example of S1 responses recorded in the same mouse before, during, and 30–180 min after ischemia applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 60 × 60 pixels shown in the second panel. (c) Relative amplitudes of S1 responses during and after hindpaw ischemia. (d) Example of S1 responses recorded before and at 60 min after sham treatment. (e) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of saline alone. (f) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (g) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, hindpaw ischemia with spinal application of saline alone, or hindpaw ischemia with spinal application of 10 nM LY354740.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4499883&req=5

f3: Potentiation of the S1 responses after ischemic treatment.(a) Example of contralateral S1 responses elicited by vibratory stimulation applied to the left hindpaw. (b) Example of S1 responses recorded in the same mouse before, during, and 30–180 min after ischemia applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 60 × 60 pixels shown in the second panel. (c) Relative amplitudes of S1 responses during and after hindpaw ischemia. (d) Example of S1 responses recorded before and at 60 min after sham treatment. (e) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of saline alone. (f) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (g) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, hindpaw ischemia with spinal application of saline alone, or hindpaw ischemia with spinal application of 10 nM LY354740.

Mentions: Flavoprotein fluorescence responses elicited by hindpaw stimulation appeared in the contralateral S1 (Fig. 3a). The initial time course of S1 responses elicited by hindpaw stimulation was similar to that of spinal responses, while hemodynamic responses obscured the later phase of the responses (Supplementary Figs S3). Although neural responses in S1 are arranged according to somatotopic maps over a large scale262829, the responses elicited by stimulation of each toe were not clearly separated, and no fine somatotopic map was found (Supplementary Figs S3). When a pressure of 250 mmHg was applied to the thigh, S1 responses were almost completely abolished (Fig. 3b). However, the responses reappeared and were potentiated after hindpaw ischemia (Fig. 3b,c). The potentiation was maintained up to 3 h after hindpaw ischemia. The relative amplitudes at 1 h after hindpaw ischemia (165 ± 18%, n = 13) were significantly larger than those in sham-treated mice (99 ± 4%, n = 8, P < 0.003, Fig. 3d,g). Potentiation of S1 responses after ischemic treatment was almost completely abolished by spinal application of 10 nM LY354740 (Fig. 3e,f). The relative amplitudes of S1 responses in mice with spinal application with LY354740 were 105 ± 6% (n = 9) at 1 h after hindpaw ischemia, and were significantly smaller than those in mice with spinal application of saline alone (150 ± 16%, n = 8, P < 0.007, Fig. 3g). Therefore, the suppression of S1 potentiation is likely attributable to the pharmacological effects of LY354740, but not to non-specific spinal injury caused by the drug application.


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 S1 responses after ischemic treatment.(a) Example of contralateral S1 responses elicited by vibratory stimulation applied to the left hindpaw. (b) Example of S1 responses recorded in the same mouse before, during, and 30–180 min after ischemia applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 60 × 60 pixels shown in the second panel. (c) Relative amplitudes of S1 responses during and after hindpaw ischemia. (d) Example of S1 responses recorded before and at 60 min after sham treatment. (e) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of saline alone. (f) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (g) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, hindpaw ischemia with spinal application of saline alone, 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

f3: Potentiation of the S1 responses after ischemic treatment.(a) Example of contralateral S1 responses elicited by vibratory stimulation applied to the left hindpaw. (b) Example of S1 responses recorded in the same mouse before, during, and 30–180 min after ischemia applied to the left thigh for 30 min. The response amplitudes were measured in the square window of 60 × 60 pixels shown in the second panel. (c) Relative amplitudes of S1 responses during and after hindpaw ischemia. (d) Example of S1 responses recorded before and at 60 min after sham treatment. (e) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of saline alone. (f) Example of S1 responses recorded before and at 60 min after hindpaw ischemia in a mouse with spinal application of 10 nM LY354740. (g) Comparison of the normalized response amplitudes in mice at 60 min after hindpaw ischemia, sham treatment, hindpaw ischemia with spinal application of saline alone, or hindpaw ischemia with spinal application of 10 nM LY354740.
Mentions: Flavoprotein fluorescence responses elicited by hindpaw stimulation appeared in the contralateral S1 (Fig. 3a). The initial time course of S1 responses elicited by hindpaw stimulation was similar to that of spinal responses, while hemodynamic responses obscured the later phase of the responses (Supplementary Figs S3). Although neural responses in S1 are arranged according to somatotopic maps over a large scale262829, the responses elicited by stimulation of each toe were not clearly separated, and no fine somatotopic map was found (Supplementary Figs S3). When a pressure of 250 mmHg was applied to the thigh, S1 responses were almost completely abolished (Fig. 3b). However, the responses reappeared and were potentiated after hindpaw ischemia (Fig. 3b,c). The potentiation was maintained up to 3 h after hindpaw ischemia. The relative amplitudes at 1 h after hindpaw ischemia (165 ± 18%, n = 13) were significantly larger than those in sham-treated mice (99 ± 4%, n = 8, P < 0.003, Fig. 3d,g). Potentiation of S1 responses after ischemic treatment was almost completely abolished by spinal application of 10 nM LY354740 (Fig. 3e,f). The relative amplitudes of S1 responses in mice with spinal application with LY354740 were 105 ± 6% (n = 9) at 1 h after hindpaw ischemia, and were significantly smaller than those in mice with spinal application of saline alone (150 ± 16%, n = 8, P < 0.007, Fig. 3g). Therefore, the suppression of S1 potentiation is likely attributable to the pharmacological effects of LY354740, but not to non-specific spinal injury caused by the drug application.

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