Abstract

We propose a novel application of diffuse correlation spectroscopy to evaluate microvascular malfunctions of muscle tissue affected by hyperglycemia and determine their correlation with the severity of diabetic neuropathy at a later stage. Microvascular responses of the thigh muscle and the mechanical pain threshold of the hind paw of streptozotocin-induced type I diabetic rats were continuously monitored once per week for 70 days. Significantly decreased baseline blood flow and reactive hyperemia responses were observed as early as 1 week after hyperglycemia induction. The reactive hyperemia response at 2 weeks of hyperglycemia waths highly correlated with the mechanical pain threshold at 8 weeks, at which time a decreased pain threshold was statistically confirmed in hyperglycemic rats relative to controls.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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2018 (1)

M. Ichinose, M. Nakabayashi, and Y. Ono, “Sympathoexcitation constrains vasodilation in the human skeletal muscle microvasculature during post-occlusive reactive hyperemia,” Am. J. Physiol. Heart Circ. Physiol. 315(2), H242-H253 (2018).

2017 (2)

2016 (1)

2015 (2)

2014 (1)

J. W. Albers and R. Pop-Busui, “Diabetic neuropathy: mechanisms, emerging treatments, and subtypes,” Curr. Neurol. Neurosci. Rep. 14(8), 473 (2014).
[Crossref] [PubMed]

2013 (1)

2012 (2)

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

H. Andersen, “Motor dysfunction in diabetes,” Diabetes Metab. Res. Rev. 28(1), 89–92 (2012).
[Crossref] [PubMed]

2011 (2)

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

A. M. Vincent, B. C. Callaghan, A. L. Smith, and E. L. Feldman, “Diabetic neuropathy: cellular mechanisms as therapeutic targets,” Nat. Rev. Neurol. 7(10), 573–583 (2011).
[Crossref] [PubMed]

2010 (2)

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[Crossref] [PubMed]

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

2009 (1)

R. Yamamoto-Suganuma and Y. Aso, “Relationship between post-occlusive forearm skin reactive hyperaemia and vascular disease in patients with Type 2 diabetes-a novel index for detecting micro- and macrovascular dysfunction using laser Doppler flowmetry,” Diabet. Med. 26(1), 83–88 (2009).
[Crossref] [PubMed]

2007 (1)

2005 (1)

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, and A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005).
[Crossref] [PubMed]

2004 (2)

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

T. J. Morrow, “Animal models of painful diabetic neuropathy: the STZ rat model,” Curr. Protoc. Neurosci. 9(1), 18 (2004).
[PubMed]

2003 (2)

G. J. Bennett, J. M. Chung, M. Honore, and Z. Seltzer, “Models of neuropathic pain in the rat,” Curr. Protoc. Neurosci. 9(1), 14 (2003).
[PubMed]

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

2001 (1)

N. E. Cameron, S. E. M. Eaton, M. A. Cotter, and S. Tesfaye, “Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy,” Diabetologia 44(11), 1973–1988 (2001).
[Crossref] [PubMed]

1998 (1)

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

1995 (2)

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

M. S. Patterson, S. Andersson-Engels, B. C. Wilson, and E. K. Osei, “Absorption spectroscopy in tissue-simulating materials: a theoretical and experimental study of photon paths,” Appl. Opt. 34(1), 22–30 (1995).
[Crossref] [PubMed]

1994 (1)

A. G. Harris, T. C. Skalak, and D. L. Hatchell, “Leukocyte-capillary plugging and network resistance are increased in skeletal muscle of rats with streptozotocin-induced hyperglycemia,” Int. J. Microcirc. Clin. Exp. 14(3), 159–166 (1994).
[Crossref] [PubMed]

1993 (1)

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

1991 (1)

N. E. Cameron, M. A. Cotter, and P. A. Low, “Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits,” Am. J. Physiol. 261(1), E1–E8 (1991).
[PubMed]

Abraham, P.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Akbari, C. M.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Albers, J. W.

J. W. Albers and R. Pop-Busui, “Diabetic neuropathy: mechanisms, emerging treatments, and subtypes,” Curr. Neurol. Neurosci. Rep. 14(8), 473 (2014).
[Crossref] [PubMed]

Andersen, H.

H. Andersen, “Motor dysfunction in diabetes,” Diabetes Metab. Res. Rev. 28(1), 89–92 (2012).
[Crossref] [PubMed]

Andersson-Engels, S.

Aso, Y.

R. Yamamoto-Suganuma and Y. Aso, “Relationship between post-occlusive forearm skin reactive hyperaemia and vascular disease in patients with Type 2 diabetes-a novel index for detecting micro- and macrovascular dysfunction using laser Doppler flowmetry,” Diabet. Med. 26(1), 83–88 (2009).
[Crossref] [PubMed]

Baker, W. B.

Beauvoit, B.

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

Bennett, G. J.

G. J. Bennett, J. M. Chung, M. Honore, and Z. Seltzer, “Models of neuropathic pain in the rat,” Curr. Protoc. Neurosci. 9(1), 14 (2003).
[PubMed]

Bernardi, L.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Bi, R.

R. Bi, J. Dong, C. L. Poh, and K. Lee, “Optical methods for blood perfusion measurement--theoretical comparison among four different modalities,” J. Opt. Soc. Am. A 32(5), 860–866 (2015).
[Crossref] [PubMed]

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

Boulton, A. J.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Brown, L.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Burstow, D.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Callaghan, B. C.

A. M. Vincent, B. C. Callaghan, A. L. Smith, and E. L. Feldman, “Diabetic neuropathy: cellular mechanisms as therapeutic targets,” Nat. Rev. Neurol. 7(10), 573–583 (2011).
[Crossref] [PubMed]

Cameron, N. E.

N. E. Cameron, S. E. M. Eaton, M. A. Cotter, and S. Tesfaye, “Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy,” Diabetologia 44(11), 1973–1988 (2001).
[Crossref] [PubMed]

N. E. Cameron, M. A. Cotter, and P. A. Low, “Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits,” Am. J. Physiol. 261(1), E1–E8 (1991).
[PubMed]

Chance, B.

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, and A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005).
[Crossref] [PubMed]

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

Cheng, R.

Choe, R.

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[Crossref] [PubMed]

Chrzan, J. S.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Chung, J. M.

G. J. Bennett, J. M. Chung, M. Honore, and Z. Seltzer, “Models of neuropathic pain in the rat,” Curr. Protoc. Neurosci. 9(1), 14 (2003).
[PubMed]

Colombo, L.

Contini, D.

Cotter, M. A.

N. E. Cameron, S. E. M. Eaton, M. A. Cotter, and S. Tesfaye, “Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy,” Diabetologia 44(11), 1973–1988 (2001).
[Crossref] [PubMed]

N. E. Cameron, M. A. Cotter, and P. A. Low, “Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits,” Am. J. Physiol. 261(1), E1–E8 (1991).
[PubMed]

Daugherty, A.

DeGirolami, U.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Demiot, C.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Detre, J. A.

Donaghue, V. M.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Dong, J.

R. Bi, J. Dong, C. L. Poh, and K. Lee, “Optical methods for blood perfusion measurement--theoretical comparison among four different modalities,” J. Opt. Soc. Am. A 32(5), 860–866 (2015).
[Crossref] [PubMed]

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

Du, G. H.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Durduran, T.

Dyck, P. J.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Eaton, S. E. M.

N. E. Cameron, S. E. M. Eaton, M. A. Cotter, and S. Tesfaye, “Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy,” Diabetologia 44(11), 1973–1988 (2001).
[Crossref] [PubMed]

Erdmann, R.

Evans, S. M.

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

Feldman, E. L.

A. M. Vincent, B. C. Callaghan, A. L. Smith, and E. L. Feldman, “Diabetic neuropathy: cellular mechanisms as therapeutic targets,” Nat. Rev. Neurol. 7(10), 573–583 (2011).
[Crossref] [PubMed]

Finney, D.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Floyd, T. F.

Freeman, R.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Fromy, B.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Gannon, K.

Gong, L. L.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Harris, A. G.

A. G. Harris, T. C. Skalak, and D. L. Hatchell, “Leukocyte-capillary plugging and network resistance are increased in skeletal muscle of rats with streptozotocin-induced hyperglycemia,” Int. J. Microcirc. Clin. Exp. 14(3), 159–166 (1994).
[Crossref] [PubMed]

Hatchell, D. L.

A. G. Harris, T. C. Skalak, and D. L. Hatchell, “Leukocyte-capillary plugging and network resistance are increased in skeletal muscle of rats with streptozotocin-induced hyperglycemia,” Int. J. Microcirc. Clin. Exp. 14(3), 159–166 (1994).
[Crossref] [PubMed]

Ho, J. H.

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

Hoey, A. J.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Honore, M.

G. J. Bennett, J. M. Chung, M. Honore, and Z. Seltzer, “Models of neuropathic pain in the rat,” Curr. Protoc. Neurosci. 9(1), 14 (2003).
[PubMed]

Horowitz, M.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Ichinose, M.

M. Ichinose, M. Nakabayashi, and Y. Ono, “Sympathoexcitation constrains vasodilation in the human skeletal muscle microvasculature during post-occlusive reactive hyperemia,” Am. J. Physiol. Heart Circ. Physiol. 315(2), H242-H253 (2018).

Jenkins, T. W.

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

Kahler, K.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Kavuri, V.

Kelly, S. T.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Kempler, P.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Ko, T.

Koïtka, A.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Lauria, G.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Lech, G.

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, and A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005).
[Crossref] [PubMed]

Lee, K.

R. Bi, J. Dong, C. L. Poh, and K. Lee, “Optical methods for blood perfusion measurement--theoretical comparison among four different modalities,” J. Opt. Soc. Am. A 32(5), 860–866 (2015).
[Crossref] [PubMed]

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

Lefthériotis, G.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Li, Z.

LoGerfo, F. W.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Low, P. A.

N. E. Cameron, M. A. Cotter, and P. A. Low, “Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits,” Am. J. Physiol. 261(1), E1–E8 (1991).
[PubMed]

Luu, T.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Malik, R. A.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Martinenghi, E.

McIntyre, S. F.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Miller, E. E.

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

Minnema, J.

Mohler, E. R.

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, and A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005).
[Crossref] [PubMed]

Mora, A. D.

Morrow, T. J.

T. J. Morrow, “Animal models of painful diabetic neuropathy: the STZ rat model,” Curr. Protoc. Neurosci. 9(1), 18 (2004).
[PubMed]

Mullen, M. T.

Nakabayashi, M.

M. Ichinose, M. Nakabayashi, and Y. Ono, “Sympathoexcitation constrains vasodilation in the human skeletal muscle microvasculature during post-occlusive reactive hyperemia,” Am. J. Physiol. Heart Circ. Physiol. 315(2), H242-H253 (2018).

M. Nakabayashi and Y. Ono, “Detection of Blood Flow Speed in Shallow and Deep Tissues Using Diffuse Correlation Spectroscopy,” Advanced Biomedical Engineering 6(0), 53–58 (2017).
[Crossref]

Ong, L.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Ono, Y.

M. Ichinose, M. Nakabayashi, and Y. Ono, “Sympathoexcitation constrains vasodilation in the human skeletal muscle microvasculature during post-occlusive reactive hyperemia,” Am. J. Physiol. Heart Circ. Physiol. 315(2), H242-H253 (2018).

M. Nakabayashi and Y. Ono, “Detection of Blood Flow Speed in Shallow and Deep Tissues Using Diffuse Correlation Spectroscopy,” Advanced Biomedical Engineering 6(0), 53–58 (2017).
[Crossref]

Osei, E. K.

Pagliazzi, M.

Parthasarathy, A. B.

Patterson, M. S.

Pifferi, A.

Poh, C. L.

Pop-Busui, R.

J. W. Albers and R. Pop-Busui, “Diabetic neuropathy: mechanisms, emerging treatments, and subtypes,” Curr. Neurol. Neurosci. Rep. 14(8), 473 (2014).
[Crossref] [PubMed]

Primavera, J.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Qiang, G. F.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Rayman, G.

P. R. Vas, S. Sharma, and G. Rayman, “Distal sensorimotor neuropathy: improvements in diagnosis,” Rev. Diabet. Stud. 12(1-2), 29–47 (2015).
[Crossref] [PubMed]

Rendell, M. S.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Ross, F. B.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Saumet, J. L.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Schenkel, S.

Schmid, K.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Sekar, S. K. V.

Seltzer, Z.

G. J. Bennett, J. M. Chung, M. Honore, and Z. Seltzer, “Models of neuropathic pain in the rat,” Curr. Protoc. Neurosci. 9(1), 14 (2003).
[PubMed]

Sharma, S.

P. R. Vas, S. Sharma, and G. Rayman, “Distal sensorimotor neuropathy: improvements in diagnosis,” Rev. Diabet. Stud. 12(1-2), 29–47 (2015).
[Crossref] [PubMed]

Shin, H.

Sigaudo-Roussel, D.

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

Skalak, T. C.

A. G. Harris, T. C. Skalak, and D. L. Hatchell, “Leukocyte-capillary plugging and network resistance are increased in skeletal muscle of rats with streptozotocin-induced hyperglycemia,” Int. J. Microcirc. Clin. Exp. 14(3), 159–166 (1994).
[Crossref] [PubMed]

Smith, A. L.

A. M. Vincent, B. C. Callaghan, A. L. Smith, and E. L. Feldman, “Diabetic neuropathy: cellular mechanisms as therapeutic targets,” Nat. Rev. Neurol. 7(10), 573–583 (2011).
[Crossref] [PubMed]

Smith, M. T.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Soo, K. C.

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

Spallone, V.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Sun, L.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Terando, J. V.

M. S. Rendell, S. T. Kelly, D. Finney, T. Luu, K. Kahler, S. F. McIntyre, and J. V. Terando, “Decreased skin blood flow early in the course of streptozotocin-induced diabetes mellitus in the rat,” Diabetologia 36(10), 907–911 (1993).
[Crossref] [PubMed]

Tesfaye, S.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

N. E. Cameron, S. E. M. Eaton, M. A. Cotter, and S. Tesfaye, “Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy,” Diabetologia 44(11), 1973–1988 (2001).
[Crossref] [PubMed]

Thong, P. S.

J. Dong, R. Bi, J. H. Ho, P. S. Thong, K. C. Soo, and K. Lee, “Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator,” J. Biomed. Opt. 17(9), 097004 (2012).
[Crossref] [PubMed]

Torricelli, A.

Valensi, P.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Vas, P. R.

P. R. Vas, S. Sharma, and G. Rayman, “Distal sensorimotor neuropathy: improvements in diagnosis,” Rev. Diabet. Stud. 12(1-2), 29–47 (2015).
[Crossref] [PubMed]

Veves, A.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Vincent, A. M.

A. M. Vincent, B. C. Callaghan, A. L. Smith, and E. L. Feldman, “Diabetic neuropathy: cellular mechanisms as therapeutic targets,” Nat. Rev. Neurol. 7(10), 573–583 (2011).
[Crossref] [PubMed]

Vinik, A.

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Wang, D.

Wang, J.

Wei, M.

M. Wei, L. Ong, M. T. Smith, F. B. Ross, K. Schmid, A. J. Hoey, D. Burstow, and L. Brown, “The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes,” Heart Lung Circ. 12(1), 44–50 (2003).
[Crossref] [PubMed]

Wilson, B. C.

Xu, P.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Yamamoto-Suganuma, R.

R. Yamamoto-Suganuma and Y. Aso, “Relationship between post-occlusive forearm skin reactive hyperaemia and vascular disease in patients with Type 2 diabetes-a novel index for detecting micro- and macrovascular dysfunction using laser Doppler flowmetry,” Diabet. Med. 26(1), 83–88 (2009).
[Crossref] [PubMed]

Yang, X. Y.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Yodh, A. G.

D. Wang, A. B. Parthasarathy, W. B. Baker, K. Gannon, V. Kavuri, T. Ko, S. Schenkel, Z. Li, Z. Li, M. T. Mullen, J. A. Detre, and A. G. Yodh, “Fast blood flow monitoring in deep tissues with real-time software correlators,” Biomed. Opt. Express 7(3), 776–797 (2016).
[Crossref] [PubMed]

T. Durduran, R. Choe, W. B. Baker, and A. G. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[Crossref] [PubMed]

G. Yu, T. F. Floyd, T. Durduran, C. Zhou, J. Wang, J. A. Detre, and A. G. Yodh, “Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI,” Opt. Express 15(3), 1064–1075 (2007).
[Crossref] [PubMed]

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, and A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005).
[Crossref] [PubMed]

Yu, G.

Zacharoulis, D.

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Zhang, L.

X. Y. Yang, L. Sun, P. Xu, L. L. Gong, G. F. Qiang, L. Zhang, and G. H. Du, “Effects of salvianolic scid A on plantar microcirculation and peripheral nerve function in diabetic rats,” Eur. J. Pharmacol. 665(1-3), 40–46 (2011).
[Crossref] [PubMed]

Zhang, X.

Zhou, C.

G. Yu, T. F. Floyd, T. Durduran, C. Zhou, J. Wang, J. A. Detre, and A. G. Yodh, “Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI,” Opt. Express 15(3), 1064–1075 (2007).
[Crossref] [PubMed]

G. Yu, T. Durduran, G. Lech, C. Zhou, B. Chance, E. R. Mohler, and A. G. Yodh, “Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies,” J. Biomed. Opt. 10(2), 024027 (2005).
[Crossref] [PubMed]

Advanced Biomedical Engineering (1)

M. Nakabayashi and Y. Ono, “Detection of Blood Flow Speed in Shallow and Deep Tissues Using Diffuse Correlation Spectroscopy,” Advanced Biomedical Engineering 6(0), 53–58 (2017).
[Crossref]

Am. J. Physiol. (1)

N. E. Cameron, M. A. Cotter, and P. A. Low, “Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits,” Am. J. Physiol. 261(1), E1–E8 (1991).
[PubMed]

Am. J. Physiol. Heart Circ. Physiol. (1)

M. Ichinose, M. Nakabayashi, and Y. Ono, “Sympathoexcitation constrains vasodilation in the human skeletal muscle microvasculature during post-occlusive reactive hyperemia,” Am. J. Physiol. Heart Circ. Physiol. 315(2), H242-H253 (2018).

Anal. Biochem. (1)

B. Beauvoit, S. M. Evans, T. W. Jenkins, E. E. Miller, and B. Chance, “Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors,” Anal. Biochem. 226(1), 167–174 (1995).
[Crossref] [PubMed]

Appl. Opt. (2)

Biomed. Opt. Express (2)

Curr. Neurol. Neurosci. Rep. (1)

J. W. Albers and R. Pop-Busui, “Diabetic neuropathy: mechanisms, emerging treatments, and subtypes,” Curr. Neurol. Neurosci. Rep. 14(8), 473 (2014).
[Crossref] [PubMed]

Curr. Protoc. Neurosci. (2)

T. J. Morrow, “Animal models of painful diabetic neuropathy: the STZ rat model,” Curr. Protoc. Neurosci. 9(1), 18 (2004).
[PubMed]

G. J. Bennett, J. M. Chung, M. Honore, and Z. Seltzer, “Models of neuropathic pain in the rat,” Curr. Protoc. Neurosci. 9(1), 14 (2003).
[PubMed]

Diabet. Med. (1)

R. Yamamoto-Suganuma and Y. Aso, “Relationship between post-occlusive forearm skin reactive hyperaemia and vascular disease in patients with Type 2 diabetes-a novel index for detecting micro- and macrovascular dysfunction using laser Doppler flowmetry,” Diabet. Med. 26(1), 83–88 (2009).
[Crossref] [PubMed]

Diabetes (2)

D. Sigaudo-Roussel, C. Demiot, B. Fromy, A. Koïtka, G. Lefthériotis, P. Abraham, and J. L. Saumet, “Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice,” Diabetes 53(6), 1564–1569 (2004).
[Crossref] [PubMed]

A. Veves, C. M. Akbari, J. Primavera, V. M. Donaghue, D. Zacharoulis, J. S. Chrzan, U. DeGirolami, F. W. LoGerfo, and R. Freeman, “Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration,” Diabetes 47(3), 457–463 (1998).
[Crossref] [PubMed]

Diabetes Care (1)

S. Tesfaye, A. J. Boulton, P. J. Dyck, R. Freeman, M. Horowitz, P. Kempler, G. Lauria, R. A. Malik, V. Spallone, A. Vinik, L. Bernardi, P. Valensi, and Toronto Diabetic Neuropathy Expert Group, “Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments,” Diabetes Care 33(10), 2285–2293 (2010).
[Crossref] [PubMed]

Diabetes Metab. Res. Rev. (1)

H. Andersen, “Motor dysfunction in diabetes,” Diabetes Metab. Res. Rev. 28(1), 89–92 (2012).
[Crossref] [PubMed]

Diabetologia (2)

N. E. Cameron, S. E. M. Eaton, M. A. Cotter, and S. Tesfaye, “Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy,” Diabetologia 44(11), 1973–1988 (2001).
[Crossref] [PubMed]

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Figures (5)

Fig. 1
Fig. 1 Experimental setting for the reactive hyperemia test of a rat hind limb. (a) Rat is anesthetized in side lying position on the mesh grid, with its left hind limb fixed in a customized limb mold made of styrene foam. A strip of surgical tape is used to seal the limb into the mold during the DCS measurement. An elastic band is wrapped around the root of the left hind limb for occlusion. (b) A silicon optode guide is embedded in the limb mold. (c) Emitter and detector optical probes contact the skin surface through the holes of the optode guide from the bottom.
Fig. 2
Fig. 2 Representative time-course of the blood flow index (BFI) and microvascular parameters obtained by the reactive hyperemia test. The entire test consisted of 1 minute of rest, 3 minutes of blood flow occlusion, and 6 minutes of post-occlusion rest. We evaluated the mean BFI value at rest (baseline), peak BFI value after releasing from occlusion (post-occlusive reactive hyperemia (PORH) peak), time to PORH peak after releasing from occlusion (Tp), and half-decay time from the PORH peak (50% decay time). Normalized PORH peaks were also calculated by dividing the peak BFI value by the baseline value.
Fig. 3
Fig. 3 Changes in the (a) body weight, (b) blood glucose concentrations, (c) mechanical pain thresholds, (d-h) microvascular responses to the reactive hyperemia test, and (i) cumulative number of diabetic rats showing allodynia throughout the experimental period in control and diabetic rats. Data obtained in the first 2 measurements prior to the STZ/vehicle administration were averaged and used as baseline values (pre). Error bars show standard errors. The asterisk (*) indicates statistically significant changes from pre. The dagger (†) indicates a statistically significant difference between the control and diabetic rats at the corresponding time period. BFI: blood flow index, PORH: post-occlusive reactive hyperemia, Tp: time to peak.
Fig. 4
Fig. 4 Superimposed time trace of the blood flow index (BFI) during reactive hyperemia testing in rats in the control (a) and diabetic (b) groups across different experimental days. Vertical dotted lines show durations of occlusion. Solid lines show mean values, and shaded areas show standard errors.
Fig. 5
Fig. 5 Correlations between microvascular responses during reactive hyperemia testing in the early stage of hyperglycemia and the severity of diabetic neuropathy during the later stages. (a) Relationship between the PORH peak BFI in the diabetic rats on day 14 and the logarithm of mechanical pain thresholds on day 56, which showed the highest correlation coefficient among the combinations tested. (b) Summary of the correlation coefficients between microvascular responses on each experimental day and the logarithm of mechanical pain thresholds on day 56. Horizontal dotted lines show the correlation coefficient values with statistical significance (p<0.05) based on the number of subjects. BFI: blood flow index, PORH: post-occlusive reactive hyperemia, Tp: time to peak.

Equations (1)

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G 2 ( r, τ )= <I( r,  t )*I( r,  t+τ )> <I( r,  t ) > 2

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