Neural strain: Difference between revisions

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'''Neural strain''' from biomechanical stress can cause profound [[metabolic]] changes in the affected tissue due to alterations in the morphology of the cell membrane and decreased blood flow<ref name=":0" /><ref name=":1" /><ref name=":3" /><ref name=":4" /><ref name=":6" /><ref name=":7" /><ref name=":8" /> causing hypoxia. Injury can result from tensile, compressive, or shear stress or as a combination of stresses.<ref name=":0">{{Cite journal | last = Boyd | first = Benjamin S. | last2 = Topp | first2 = Kimberly S. | date = 2006-01-01 | title = Structure and Biomechanics of Peripheral Nerves: Nerve Responses to Physical Stresses and Implications for Physical Therapist Practice|url=https://academic.oup.com/ptj/article/86/1/92/2805155|journal=Physical Therapy|language=en|volume=86|issue=1 | pages = 92–109|doi=10.1093/ptj/86.1.92|issn=0031-9023}}</ref> Metabolic changes include a shift to anaerobic metabolism, resulting in increased [[lactate dehydrogenase]]<ref name=":9">{{Cite journal | last = Laplaca | first = Michelle C. | last2 = Lee | first2=Virginia M.-Y. | last3 = Thibault | first3 = Lawrence E. | date = 1997-06-01 | title = An In Vitro Model of Traumatic Neuronal Injury: Loading Rate-Dependent Changes in Acute Cytosolic Calcium and Lactate Dehydrogenase Release|url=https://www.liebertpub.com/doi/abs/10.1089/neu.1997.14.355|journal=Journal of Neurotrauma|volume=14|issue=6|pages=355–368|doi=10.1089/neu.1997.14.355|issn=0897-7151}}</ref> and reduced ATP production,<ref name=":10" /> and changes in electrolyte balance, including an increase in intracellular [[calcium]] in a dose-dependent manner.<ref>{{Cite journal | last = Cargill | first = Robert S. | last2 = Geddes | first2=Donna M. | date = 2001-06-01 | title = An in Vitro Model of Neural Trauma: Device Characterization and Calcium Response to Mechanical Stretch|url=https://biomechanical.asmedigitalcollection.asme.org/article.aspx?articleid=1405653|journal=Journal of Biomechanical Engineering|volume=123|issue=3|pages=247–255|doi=10.1115/1.1374201|issn=0148-0731}}</ref><ref>{{Cite journal | last = Cargill | first = Robert S. | last2 = Thibault | first2 = Lawrence E. | date = 1996-07-01 | title = Acute Alterations in [Ca2+]i in NG108-15 Cells Subjected to High Strain Rate Deformation and Chemical Hypoxia: An in Vitro Model for Neural Trauma|url=https://www.liebertpub.com/doi/abs/10.1089/neu.1996.13.395|journal=Journal of Neurotrauma|volume=13|issue=7|pages=395–407|doi=10.1089/neu.1996.13.395|issn=0897-7151}}</ref><ref name=":9" />  
'''Neural strain''' from biomechanical stress can cause profound [[metabolic]] changes in the affected tissue due to alterations in the morphology of the cell membrane and decreased blood flow<ref name=":0" /><ref name=":1" /><ref name=":3" /><ref name=":4" /><ref name=":6" /><ref name=":7" /><ref name=":8" /> causing hypoxia. Injury can result from tensile, compressive, or shear stress or as a combination of stresses.<ref name=":0">{{Cite journal | last = Boyd | first = Benjamin S. | last2 = Topp | first2 = Kimberly S. | date = 2006-01-01 | title = Structure and Biomechanics of Peripheral Nerves: Nerve Responses to Physical Stresses and Implications for Physical Therapist Practice|url=https://academic.oup.com/ptj/article/86/1/92/2805155|journal=Physical Therapy|language=en|volume=86|issue=1 | pages = 92–109|doi=10.1093/ptj/86.1.92|issn=0031-9023}}</ref> Metabolic changes include a shift to anaerobic metabolism, resulting in increased [[lactate dehydrogenase]]<ref name=":9">{{Cite journal | last = Laplaca | first = Michelle C. | last2 = Lee | first2 = Virginia M.-Y. | last3 = Thibault | first3 = Lawrence E. | date = 1997-06-01 | title = An In Vitro Model of Traumatic Neuronal Injury: Loading Rate-Dependent Changes in Acute Cytosolic Calcium and Lactate Dehydrogenase Release|url=https://www.liebertpub.com/doi/abs/10.1089/neu.1997.14.355|journal=Journal of Neurotrauma|volume=14|issue=6|pages=355–368|doi=10.1089/neu.1997.14.355|issn=0897-7151}}</ref> and reduced ATP production,<ref name=":10" /> and changes in electrolyte balance, including an increase in intracellular [[calcium]] in a dose-dependent manner.<ref>{{Cite journal | last = Cargill | first = Robert S. | last2 = Geddes | first2 = Donna M. | date = 2001-06-01 | title = An in Vitro Model of Neural Trauma: Device Characterization and Calcium Response to Mechanical Stretch|url=https://biomechanical.asmedigitalcollection.asme.org/article.aspx?articleid=1405653|journal=Journal of Biomechanical Engineering|volume=123|issue=3|pages=247–255|doi=10.1115/1.1374201|issn=0148-0731}}</ref><ref>{{Cite journal | last = Cargill | first = Robert S. | last2 = Thibault | first2 = Lawrence E. | date = 1996-07-01 | title = Acute Alterations in [Ca2+]i in NG108-15 Cells Subjected to High Strain Rate Deformation and Chemical Hypoxia: An in Vitro Model for Neural Trauma|url=https://www.liebertpub.com/doi/abs/10.1089/neu.1996.13.395|journal=Journal of Neurotrauma|volume=13|issue=7|pages=395–407|doi=10.1089/neu.1996.13.395|issn=0897-7151}}</ref><ref name=":9" />  


=== Tension ===
=== Tension ===


In animal models, stretching or tension of nerves results in substantially reduced blood flow.<ref name=":0" /><ref name=":1">{{Cite journal | last = Clark | first = William L. | last2 = Trumble | first2=Thomas E. | last3 = Swiontkowski | first3 = Mark F. | last4 = Tencer | first4=Allan F. | date = 1992-07-01 | title = Nerve tension and blood flow in a rat model of immediate and delayed repairs|url=http://www.sciencedirect.com/science/article/pii/036350239290316H|journal=The Journal of Hand Surgery|volume=17|issue=4 | pages = 677–687|doi=10.1016/0363-5023(92)90316-H|issn=0363-5023}}</ref><ref name=":3">{{Cite journal | last = Clark | first = William L. | last2 = Trumble | first2=Thomas E. | last3 = Swiontkowski | first3 = Mark F. | last4 = Tencer | first4=Allan F. | date = 1992-07-01 | title = Nerve tension and blood flow in a rat model of immediate and delayed repairs|url=http://www.sciencedirect.com/science/article/pii/036350239290316H|journal=The Journal of Hand Surgery|volume=17|issue=4 | pages = 677–687|doi=10.1016/0363-5023(92)90316-H|issn=0363-5023}}</ref><ref name=":4">{{Cite journal | last = Driscoll | first = Peter J. | last2 = Glasby | first2 = Michael A. | last3 = Lawson | first3=Graham M. | date = 2002 | title = An in vivo study of peripheral nerves in continuity: biomechanical and physiological responses to elongation | url =https://onlinelibrary.wiley.com/doi/abs/10.1016/S0736-0266%2801%2900104-8|journal=Journal of Orthopaedic Research|language=en|volume=20|issue=2|pages=370–375|doi=10.1016/S0736-0266(01)00104-8|issn=1554-527X}}</ref><ref name=":6">{{Cite journal | last = Tanoue | first = M. | last2 = Yamaga | first2 = M. | last3 = Ide | first3 = J. | last4 = Takagi | first4 = K. | date = Jun 1996 | title = Acute stretching of peripheral nerves inhibits retrograde axonal transport|url=https://www.ncbi.nlm.nih.gov/pubmed/8771477|journal=Journal of Hand Surgery (Edinburgh, Scotland)|volume=21|issue=3|pages=358–363|issn=0266-7681|pmid=8771477}}</ref><ref name=":7">{{Cite journal | last = Ogata | first = K. | last2 = Naito | first2 = M. | date = Feb 1986 | title = Blood flow of peripheral nerve effects of dissection, stretching and compression | url =https://www.ncbi.nlm.nih.gov/pubmed/3958526|journal=Journal of Hand Surgery (Edinburgh, Scotland)|volume=11|issue=1|pages=10–14|issn=0266-7681|pmid=3958526}}</ref><ref name=":8">{{Cite journal | last= Jou | first = I. M. | last2 = Lai | first2 = K.A. | last3 = Shen | first3=C.L. |  last4 = Yamano | first4 = Y. | date = Jan 2000 | title = Changes in conduction, blood flow, histology, and neurological status following acute nerve-stretch injury induced by femoral lengthening | url =https://www.ncbi.nlm.nih.gov/pubmed/10716291|journal=Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society|volume=18|issue=1|pages=149–155|doi=10.1002/jor.1100180121|issn=0736-0266|pmid=10716291}}</ref><ref>{{Cite journal | last = Ogata | first = Kosuke | last2 = Naito | first2 = Masatoshi|date = 1986-02-01 | title = Blood flow of peripheral nerve effects of dissection stretching and compression | url =http://www.sciencedirect.com/science/article/pii/0266768186900033|journal=The Journal of Hand Surgery: British & European Volume|volume=11|issue=1|pages=10–14|doi=10.1016/0266-7681(86)90003-3|issn=0266-7681}}</ref> Tension impairs nerve regeneration.<ref>{{Cite journal | last = Sunderland | first = Ian R.P. | last2 = Brenner | first2 = Michael J. | last3 = Singham | first3 = Janakie | last4 = Rickman | first4=Susan R. | last5 = Hunter | first5=Daniel A. | last6 = Mackinnon | first6 = Susan E. | date = Oct 2004 | title = Effect of Tension on Nerve Regeneration in Rat Sciatic Nerve Transection Model|url=https://journals.lww.com/annalsplasticsurgery/Abstract/2004/10000/Effect_of_Tension_on_Nerve_Regeneration_in_Rat.16.aspx|journal=Annals of Plastic Surgery|language=en-US|volume=53|issue=4|pages=382|doi=10.1097/01.sap.0000125502.63302.47|issn=0148-7043}}</ref>  
In animal models, stretching or tension of nerves results in substantially reduced blood flow.<ref name=":0" /><ref name=":1">{{Cite journal | last = Clark | first = William L. | last2 = Trumble | first2 = Thomas E. | last3 = Swiontkowski | first3 = Mark F. | last4 = Tencer | first4 = Allan F. | date = 1992-07-01 | title = Nerve tension and blood flow in a rat model of immediate and delayed repairs|url=http://www.sciencedirect.com/science/article/pii/036350239290316H|journal=The Journal of Hand Surgery|volume=17|issue=4 | pages = 677–687|doi=10.1016/0363-5023(92)90316-H|issn=0363-5023}}</ref><ref name=":3">{{Cite journal | last = Clark | first = William L. | last2 = Trumble | first2 = Thomas E. | last3 = Swiontkowski | first3 = Mark F. | last4 = Tencer | first4 = Allan F. | date = 1992-07-01 | title = Nerve tension and blood flow in a rat model of immediate and delayed repairs|url=http://www.sciencedirect.com/science/article/pii/036350239290316H|journal=The Journal of Hand Surgery|volume=17|issue=4 | pages = 677–687|doi=10.1016/0363-5023(92)90316-H|issn=0363-5023}}</ref><ref name=":4">{{Cite journal | last = Driscoll | first = Peter J. | last2 = Glasby | first2 = Michael A. | last3 = Lawson | first3 = Graham M. | date = 2002 | title = An in vivo study of peripheral nerves in continuity: biomechanical and physiological responses to elongation | url =https://onlinelibrary.wiley.com/doi/abs/10.1016/S0736-0266%2801%2900104-8|journal=Journal of Orthopaedic Research|language=en|volume=20|issue=2|pages=370–375|doi=10.1016/S0736-0266(01)00104-8|issn=1554-527X}}</ref><ref name=":6">{{Cite journal | last = Tanoue | first = M. | last2 = Yamaga | first2 = M. | last3 = Ide | first3 = J. | last4 = Takagi | first4 = K. | date = Jun 1996 | title = Acute stretching of peripheral nerves inhibits retrograde axonal transport|url=https://www.ncbi.nlm.nih.gov/pubmed/8771477|journal=Journal of Hand Surgery (Edinburgh, Scotland)|volume=21|issue=3|pages=358–363|issn=0266-7681|pmid=8771477}}</ref><ref name=":7">{{Cite journal | last = Ogata | first = K. | last2 = Naito | first2 = M. | date = Feb 1986 | title = Blood flow of peripheral nerve effects of dissection, stretching and compression | url =https://www.ncbi.nlm.nih.gov/pubmed/3958526|journal=Journal of Hand Surgery (Edinburgh, Scotland)|volume=11|issue=1|pages=10–14|issn=0266-7681|pmid=3958526}}</ref><ref name=":8">{{Cite journal | last= Jou | first = I.M. | last2 = Lai | first2 = K.A. | last3 = Shen | first3 = C.L. |  last4 = Yamano | first4 = Y. | date = Jan 2000 | title = Changes in conduction, blood flow, histology, and neurological status following acute nerve-stretch injury induced by femoral lengthening | url =https://www.ncbi.nlm.nih.gov/pubmed/10716291|journal=Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society|volume=18|issue=1|pages=149–155|doi=10.1002/jor.1100180121|issn=0736-0266|pmid=10716291}}</ref><ref>{{Cite journal | last = Ogata | first = Kosuke | last2 = Naito | first2 = Masatoshi | date = 1986-02-01 | title = Blood flow of peripheral nerve effects of dissection stretching and compression | url =http://www.sciencedirect.com/science/article/pii/0266768186900033|journal=The Journal of Hand Surgery: British & European Volume|volume=11|issue=1|pages=10–14|doi=10.1016/0266-7681(86)90003-3|issn=0266-7681}}</ref> Tension impairs nerve regeneration.<ref>{{Cite journal | last = Sunderland | first = Ian R.P. | last2 = Brenner | first2 = Michael J. | last3 = Singham | first3 = Janakie | last4 = Rickman | first4 = Susan R. | last5 = Hunter | first5 = Daniel A. | last6 = Mackinnon | first6 = Susan E. | date = Oct 2004 | title = Effect of Tension on Nerve Regeneration in Rat Sciatic Nerve Transection Model|url=https://journals.lww.com/annalsplasticsurgery/Abstract/2004/10000/Effect_of_Tension_on_Nerve_Regeneration_in_Rat.16.aspx|journal=Annals of Plastic Surgery|language=en-US|volume=53|issue=4|pages=382|doi=10.1097/01.sap.0000125502.63302.47|issn=0148-7043}}</ref>  


===== Tethered cord syndrome =====
===== Tethered cord syndrome =====
{{Main article|page_name=Tethered cord syndrome}}
{{Main article|page_name=Tethered cord syndrome}}
[[Tethered cord syndrome]], a condition where tissue attachments limit the movement of the spinal cord within the spinal column, is associated with impaired glucose metabolism in spinal cord tissue,<ref name=":2">{{Cite journal | last = Colohan | first = Austin R.T. | last2 = Zouros | first2=Alexander | last3 = Siddiqi | first3 = Javed | last4 = Yamada | first4=Shoko M. | last5 = Yamada | first5=Brian S. | last6 = Pezeshkpour | first6 = Gholam | last7 = Won | first7 = Daniel J. | last8 = Yamada | first8 = Shokei | date = 2007-08-01 | title = Pathophysiology of tethered cord syndrome and similar complex disorders|url=https://thejns.org/view/journals/neurosurg-focus/23/2/foc-07_08_e6.xml|journal=Neurosurgical Focus|language=en-US|volume=23|issue=2|pages=1–10|doi=10.3171/FOC-07/08/E6|issn=1092-0684}}</ref> changes in the reduction/oxidation ratio of [[cytochrome oxidase]].<ref>{{Cite journal | last = Yamada | first = Shoko M. | last2 = Won | first2=Daniel J. | last3 = Yamada | first3=Shokei | date = 2004-02-01 | title = Pathophysiology of tethered cord syndrome: correlation with symptomatology|url=https://thejns.org/view/journals/neurosurg-focus/16/2/foc.2004.16.2.7.xml|journal=Neurosurgical Focus|language=en-US|volume=16|issue=2|pages=1–5|doi=10.3171/foc.2004.16.2.7|issn=1092-0684}}</ref> and reduced ATP production.<ref name=":10">{{Cite journal | last = Sullivan | first = Stephen | last2 = Park | first2 = Paul|last3 = Stetler | first3=William R. | date = 2010-07-01 | title = Pathophysiology of adult tethered cord syndrome: review of the literature|url=https://thejns.org/view/journals/neurosurg-focus/29/1/2010.3.focus1080.xml|journal=Neurosurgical Focus|language=en-US|volume=29|issue=1| pages = E2|doi=10.3171/2010.3.FOCUS1080|issn=1092-0684}}</ref> People with tethered cord syndrome have reduced blood flow to the spinal cord.<ref name=":22">{{Cite journal | last = Colohan | first = Austin R.T. | last2 = Zouros | first2=Alexander | last3 = Siddiqi | first3 = Javed | last4 = Yamada | first4=Shoko M. | last5 = Yamada | first5=Brian S. | last6 = Pezeshkpour | first6 = Gholam | last7 = Won | first7 = Daniel J. | last8 = Yamada | first8 = Shokei | date = 2007-08-01 | title = Pathophysiology of tethered cord syndrome and similar complex disorders|url=https://thejns.org/view/journals/neurosurg-focus/23/2/foc-07_08_e6.xml|journal=Neurosurgical Focus|language=en-US|volume=23|issue=2|pages=1–10|doi=10.3171/FOC-07/08/E6|issn=1092-0684}}</ref>  
[[Tethered cord syndrome]], a condition where tissue attachments limit the movement of the spinal cord within the spinal column, is associated with impaired glucose metabolism in spinal cord tissue,<ref name=":2">{{Cite journal | last = Colohan | first = Austin R.T. | last2 = Zouros | first2 = Alexander | last3 = Siddiqi | first3 = Javed | last4 = Yamada | first4 = Shoko M. | last5 = Yamada | first5 = Brian S. | last6 = Pezeshkpour | first6 = Gholam | last7 = Won | first7 = Daniel J. | last8 = Yamada | first8 = Shokei | date = 2007-08-01 | title = Pathophysiology of tethered cord syndrome and similar complex disorders|url=https://thejns.org/view/journals/neurosurg-focus/23/2/foc-07_08_e6.xml|journal=Neurosurgical Focus|language=en-US|volume=23|issue=2|pages=1–10|doi=10.3171/FOC-07/08/E6|issn=1092-0684}}</ref> changes in the reduction/oxidation ratio of [[cytochrome oxidase]].<ref>{{Cite journal | last = Yamada | first = Shoko M. | last2 = Won | first2 = Daniel J. | last3 = Yamada | first3 = Shokei | date = 2004-02-01 | title = Pathophysiology of tethered cord syndrome: correlation with symptomatology|url=https://thejns.org/view/journals/neurosurg-focus/16/2/foc.2004.16.2.7.xml|journal=Neurosurgical Focus|language=en-US|volume=16|issue=2|pages=1–5|doi=10.3171/foc.2004.16.2.7|issn=1092-0684}}</ref> and reduced ATP production.<ref name=":10">{{Cite journal | last = Sullivan | first = Stephen | last2 = Park | first2 = Paul | last3 = Stetler | first3 = William R. | date = 2010-07-01 | title = Pathophysiology of adult tethered cord syndrome: review of the literature|url=https://thejns.org/view/journals/neurosurg-focus/29/1/2010.3.focus1080.xml|journal=Neurosurgical Focus|language=en-US|volume=29|issue=1| pages = E2|doi=10.3171/2010.3.FOCUS1080|issn=1092-0684}}</ref> People with tethered cord syndrome have reduced blood flow to the spinal cord.<ref name=":22">{{Cite journal | last = Colohan | first = Austin R.T. | last2 = Zouros | first2 = Alexander | last3 = Siddiqi | first3 = Javed | last4 = Yamada | first4 = Shoko M. | last5 = Yamada | first5 = Brian S. | last6 = Pezeshkpour | first6 = Gholam | last7 = Won | first7 = Daniel J. | last8 = Yamada | first8 = Shokei | date = 2007-08-01 | title = Pathophysiology of tethered cord syndrome and similar complex disorders|url=https://thejns.org/view/journals/neurosurg-focus/23/2/foc-07_08_e6.xml|journal=Neurosurgical Focus|language=en-US|volume=23|issue=2|pages=1–10|doi=10.3171/FOC-07/08/E6|issn=1092-0684}}</ref>  


A study of energy cost of walking in adolescents with tethered cord, as measured by oxygen uptake (VO2), found that “energy cost per metre during walking at preferred speed and physical strain were higher than in peers without disability.”<ref>{{Cite journal | last = Bruinings | first = A.L. |  last2 = Berg‐Emons | first2 = H. J. G. Van Den|last3 = Buffart | first3 = L. M. | last4 = Heijden‐Maessen | first4=H. C.M. Van Der | last5 = Roebroeck | first5 = M.E. | last6 = Stam | first6 = H.J. | date = 2007 | title=Energy cost and physical strain of daily activities in adolescents and young adults with myelomeningocele|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8749.2007.00672.x|journal=Developmental Medicine & Child Neurology|language=en|volume=49|issue=9 | pages = 672–677|doi=10.1111/j.1469-8749.2007.00672.x|issn=1469-8749}}</ref>
A study of energy cost of walking in adolescents with tethered cord, as measured by oxygen uptake (VO2), found that “energy cost per metre during walking at preferred speed and physical strain were higher than in peers without disability.”<ref>{{Cite journal | last = Bruinings | first = A.L. |  last2 = Berg‐Emons | first2 = H. J. G. Van Den | last3 = Buffart | first3 = L.M. | last4 = Heijden‐Maessen | first4 = H. C.M. Van Der | last5 = Roebroeck | first5 = M.E. | last6 = Stam | first6 = H.J. | date = 2007 | title=Energy cost and physical strain of daily activities in adolescents and young adults with myelomeningocele|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-8749.2007.00672.x|journal=Developmental Medicine & Child Neurology|language=en|volume=49|issue=9 | pages = 672–677|doi=10.1111/j.1469-8749.2007.00672.x|issn=1469-8749}}</ref>


“Traction on the caudal cord results in decreased blood flow causing metabolic derangements that culminate in motor, sensory, and urinary neurological deficits. The untethering operation restores blood flow and reverses the clinical picture in most symptomatic cases.”<ref>{{Cite journal | last = Rekate | first = Harold L. | last2 = Theodore | first2 = Nicholas|last3 = Kalani | first3 = M. Yashar | last4 = Filippidis | first4=Aristotelis S. | date = 2010-07-01 | title = Spinal cord traction, vascular compromise, hypoxia, and metabolic derangements in the pathophysiology of tethered cord syndrome|url=https://thejns.org/view/journals/neurosurg-focus/29/1/2010.3.focus1085.xml|journal=Neurosurgical Focus|language=en-US|volume=29|issue=1| pages = E9|doi=10.3171/2010.3.FOCUS1085|issn=1092-0684}}</ref>
“Traction on the caudal cord results in decreased blood flow causing metabolic derangements that culminate in motor, sensory, and urinary neurological deficits. The untethering operation restores blood flow and reverses the clinical picture in most symptomatic cases.”<ref>{{Cite journal | last = Rekate | first = Harold L. | last2 = Theodore | first2 = Nicholas | last3 = Kalani | first3 = M. Yashar | last4 = Filippidis | first4 = Aristotelis S. | date = 2010-07-01 | title = Spinal cord traction, vascular compromise, hypoxia, and metabolic derangements in the pathophysiology of tethered cord syndrome|url=https://thejns.org/view/journals/neurosurg-focus/29/1/2010.3.focus1085.xml|journal=Neurosurgical Focus|language=en-US|volume=29|issue=1| pages = E9|doi=10.3171/2010.3.FOCUS1085|issn=1092-0684}}</ref>


In a study of five children undergoing surgery for tethered cord syndrome group, spinal cord blood flow prior to untethering was a mean of 12.6 ml/min per 100 g of tissue. It increased in all cases after release to a mean of 29.4 ml/min per 100 g of tissue.<ref>{{Cite journal | last = Danto | first = Joseph | last2 = Greenberg | first2 = Burt M. | last3 = Rosenthal | first3 = Alan D. | last4 = Schneider | first4=Steven J. | date = 1993-02-01 | title = A Preliminary Report on the Use of Laser-Doppler Flowmetry during Tethered Spinal Cord Release|url=https://academic.oup.com/neurosurgery/article/32/2/214/2804055|journal=Neurosurgery|language=en|volume=32|issue=2|pages=214–218|doi=10.1227/00006123-199302000-00010|issn=0148-396X}}</ref>
In a study of five children undergoing surgery for tethered cord syndrome group, spinal cord blood flow prior to untethering was a mean of 12.6 ml/min per 100 g of tissue. It increased in all cases after release to a mean of 29.4 ml/min per 100 g of tissue.<ref>{{Cite journal | last = Danto | first = Joseph | last2 = Greenberg | first2 = Burt M. | last3 = Rosenthal | first3 = Alan D. | last4 = Schneider | first4 = Steven J. | date = 1993-02-01 | title = A Preliminary Report on the Use of Laser-Doppler Flowmetry during Tethered Spinal Cord Release|url=https://academic.oup.com/neurosurgery/article/32/2/214/2804055|journal=Neurosurgery|language=en|volume=32|issue=2|pages=214–218|doi=10.1227/00006123-199302000-00010|issn=0148-396X}}</ref>


=== Compression ===
=== Compression ===
Compression of nerves can result in low blood flow;<ref>{{Cite journal | last = Rydevik | first = B. | last2 = Lundborg | first2 = G. | last3 = Bagge | first3=U. | date = 1981-01-01 | title = Effects of graded compression on intraneural blood flow: An in vivo study on rabbit tibial nerve|url=http://www.sciencedirect.com/science/article/pii/S0363502381800032|journal=The Journal of Hand Surgery|volume=6|issue=1|pages=3–12|doi=10.1016/S0363-5023(81)80003-2|issn=0363-5023}}</ref> changes in microcirculation and ischemia;<ref>{{Cite journal | last = Rydevik | first = B. | last2 = Lundborg | first2 = G. | last3 = Bagge | first3=U. | date = 1981-01-01 | title = Effects of graded compression on intraneural blood flow: An in vivo study on rabbit tibial nerve|url=http://www.sciencedirect.com/science/article/pii/S0363502381800032|journal=The Journal of Hand Surgery|volume=6|issue=1|pages=3–12|doi=10.1016/S0363-5023(81)80003-2|issn=0363-5023}}</ref> changes in vascular permeability, edema,<ref>{{Cite journal | last = Powell | first = H. | last2 = Myers | first2 = R. | last3 = Lundborg | first3 = G. | date = 1983-12-01 | title = Nerve compression injury and increased endoneurial fluid pressure: a "miniature compartment syndrome".|url=https://jnnp.bmj.com/content/46/12/1119|journal=Journal of Neurology, Neurosurgery & Psychiatry|language=en|volume=46|issue=12|pages=1119–1124|doi=10.1136/jnnp.46.12.1119|issn=0022-3050|pmid=6663311}}</ref> axonal damage; and has been associated with demyelination.<ref name=":0" /><ref>{{Cite journal | last = Myers | first = R.R. | last2 = Powell | first2 = H.C. | date = Jul 1986 | title = Pathology of experimental nerve compression.|url=http://europepmc.org/abstract/med/3724067|journal=Laboratory investigation; a journal of technical methods and pathology|volume=55|issue=1 | pages = 91–100|issn=0023-6837|pmid=3724067}}</ref><ref>{{Cite journal | last = Dahlin | first = L.B. | last2 = Lundborg | first2 = G. | date = Jun 1992 | title = The pathophysiology of nerve compression.|url=http://europepmc.org/abstract/med/1613031|journal=Hand clinics|volume=8|issue=2|pages=215–227|issn=0749-0712|pmid=1613031}}</ref><ref>{{Cite journal | last = Dahlin | first = L.B. | last2 = Lundborg | first2 = G. | date = May 1996 | title = Anatomy, function, and pathophysiology of peripheral nerves and nerve compression.|url=http://europepmc.org/abstract/med/8724572|journal=Hand clinics|volume=12|issue=2|pages=185–193|issn=0749-0712|pmid=8724572}}</ref>
Compression of nerves can result in low blood flow;<ref>{{Cite journal | last = Rydevik | first = B. | last2 = Lundborg | first2 = G. | last3 = Bagge | first3 = U. | date = 1981-01-01 | title = Effects of graded compression on intraneural blood flow: An in vivo study on rabbit tibial nerve|url=http://www.sciencedirect.com/science/article/pii/S0363502381800032|journal=The Journal of Hand Surgery|volume=6|issue=1|pages=3–12|doi=10.1016/S0363-5023(81)80003-2|issn=0363-5023}}</ref> changes in microcirculation and ischemia;<ref>{{Cite journal | last = Rydevik | first = B. | last2 = Lundborg | first2 = G. | last3 = Bagge | first3 = U. | date = 1981-01-01 | title = Effects of graded compression on intraneural blood flow: An in vivo study on rabbit tibial nerve|url=http://www.sciencedirect.com/science/article/pii/S0363502381800032|journal=The Journal of Hand Surgery|volume=6|issue=1|pages=3–12|doi=10.1016/S0363-5023(81)80003-2|issn=0363-5023}}</ref> changes in vascular permeability, edema,<ref>{{Cite journal | last = Powell | first = H. | last2 = Myers | first2 = R. | last3 = Lundborg | first3 = G. | date = 1983-12-01 | title = Nerve compression injury and increased endoneurial fluid pressure: a "miniature compartment syndrome".|url=https://jnnp.bmj.com/content/46/12/1119|journal=Journal of Neurology, Neurosurgery & Psychiatry|language=en|volume=46|issue=12|pages=1119–1124|doi=10.1136/jnnp.46.12.1119|issn=0022-3050|pmid=6663311}}</ref> axonal damage; and has been associated with demyelination.<ref name=":0" /><ref>{{Cite journal | last = Myers | first = R.R. | last2 = Powell | first2 = H.C. | date = Jul 1986 | title = Pathology of experimental nerve compression.|url=http://europepmc.org/abstract/med/3724067|journal=Laboratory investigation; a journal of technical methods and pathology|volume=55|issue=1 | pages = 91–100|issn=0023-6837|pmid=3724067}}</ref><ref>{{Cite journal | last = Dahlin | first = L.B. | last2 = Lundborg | first2 = G. | date = Jun 1992 | title = The pathophysiology of nerve compression.|url=http://europepmc.org/abstract/med/1613031|journal=Hand clinics|volume=8|issue=2|pages=215–227|issn=0749-0712|pmid=1613031}}</ref><ref>{{Cite journal | last = Dahlin | first = L.B. | last2 = Lundborg | first2 = G. | date = May 1996 | title = Anatomy, function, and pathophysiology of peripheral nerves and nerve compression.|url=http://europepmc.org/abstract/med/8724572|journal=Hand clinics|volume=12|issue=2|pages=185–193|issn=0749-0712|pmid=8724572}}</ref>


Prologned compression can result in [[inflammation]] and activation of endoneurial fibroblasts, mast cells, and macrophages.<ref>{{Cite journal | last = Powell | first = H.C. | last2 = Myers | first2 = R.R. | date = Jul 1986 | title = Pathology of experimental nerve compression | url =https://www.ncbi.nlm.nih.gov/pubmed/3724067|journal=Laboratory Investigation; a Journal of Technical Methods and Pathology|volume=55|issue=1 | pages = 91–100|issn=0023-6837|pmid=3724067}}</ref>
Prologned compression can result in [[inflammation]] and activation of endoneurial fibroblasts, mast cells, and macrophages.<ref>{{Cite journal | last = Powell | first = H.C. | last2 = Myers | first2 = R.R. | date = Jul 1986 | title = Pathology of experimental nerve compression | url =https://www.ncbi.nlm.nih.gov/pubmed/3724067|journal=Laboratory Investigation; a Journal of Technical Methods and Pathology|volume=55|issue=1 | pages = 91–100|issn=0023-6837|pmid=3724067}}</ref>


== Diagnoses ==
== Diagnoses ==
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{{Main article|page_name=Myalgic encephalomyelitis}}
{{Main article|page_name=Myalgic encephalomyelitis}}


In a study of neuromuscular strain in ME/CFS, 60 people with ME/CFS and 20 healthy controls randomly were assigned to undergo a neuromuscular strain maneuver (“straight leg test”) or sham maneuver. Those with ME/CFS in the strain condition group had significantly increased symptoms for up to 24 hours.<ref>{{Cite journal | last = Violand | first = Richard L. | last2 = Thompson | first2=Carol B. | last3 = Moni | first3 = Malini | last4 = Marden | first4=Colleen L. | last5 = Jasion | first5=Samantha E. | last6 = Lauver | first6 = Megan | last7 = Fontaine | first7 = Kevin R. | last8 = Rowe | first8 = Peter C. | date = 2016-07-18 | title = Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159386|journal=PLOS ONE|language=en|volume=11|issue=7| pages = e0159386|doi=10.1371/journal.pone.0159386|issn=1932-6203}}</ref>
In a study of neuromuscular strain in ME/CFS, 60 people with ME/CFS and 20 healthy controls randomly were assigned to undergo a neuromuscular strain maneuver (“straight leg test”) or sham maneuver. Those with ME/CFS in the strain condition group had significantly increased symptoms for up to 24 hours.<ref>{{Cite journal | last = Violand | first = Richard L. | last2 = Thompson | first2 = Carol B. | last3 = Moni | first3 = Malini | last4 = Marden | first4 = Colleen L. | last5 = Jasion | first5 = Samantha E. | last6 = Lauver | first6 = Megan | last7 = Fontaine | first7 = Kevin R. | last8 = Rowe | first8 = Peter C. | date = 2016-07-18 | title = Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159386|journal=PLOS ONE|language=en|volume=11|issue=7| pages = e0159386|doi=10.1371/journal.pone.0159386|issn=1932-6203}}</ref>


== Mast cell activation syndrome ==
== Mast cell activation syndrome ==
{{Main article|page_name=Mast cell activation syndrome}}
{{Main article|page_name=Mast cell activation syndrome}}


[[Mast cell|Mast cells]] are distributed throughout the nervous system, including in the dura, and are known to degranulate when nervous tissue is stretched.<ref>{{Cite journal | last = Skaper | first = Stephen D. | last2 = Facci | first2 = Laura|last3 = Giusti | first3 = Pietro | date = Mar 2014 | title = Mast cells, glia and neuroinflammation: partners in crime?|url=https://www.ncbi.nlm.nih.gov/pubmed/24032675|journal=Immunology|volume=141|issue=3|pages=314–327|doi=10.1111/imm.12170|issn=1365-2567|pmc=3930370|pmid=24032675|quote=|access-date=|via=}}</ref><ref>{{Cite journal | last = Hu | first = Kenneth K. | last2 = Bruce | first2 = Marc A. | last3 = Butte | first3=Manish J. | date = 2014-05-01 | title = Spatiotemporally and mechanically controlled triggering of mast cells using atomic force microscopy|url=https://doi.org/10.1007/s12026-014-8510-7|journal=Immunologic Research|language=en|volume=58|issue=2|pages=211–217|doi=10.1007/s12026-014-8510-7|issn=1559-0755|pmc =  4154250|pmid=24777418}}</ref>
[[Mast cell|Mast cells]] are distributed throughout the nervous system, including in the dura, and are known to degranulate when nervous tissue is stretched.<ref>{{Cite journal | last = Skaper | first = Stephen D. | last2 = Facci | first2 = Laura | last3 = Giusti | first3 = Pietro | date = Mar 2014 | title = Mast cells, glia and neuroinflammation: partners in crime?|url=https://www.ncbi.nlm.nih.gov/pubmed/24032675|journal=Immunology|volume=141|issue=3|pages=314–327|doi=10.1111/imm.12170|issn=1365-2567|pmc=3930370|pmid=24032675|quote=|access-date=|via=}}</ref><ref>{{Cite journal | last = Hu | first = Kenneth K. | last2 = Bruce | first2 = Marc A. | last3 = Butte | first3 = Manish J. | date = 2014-05-01 | title = Spatiotemporally and mechanically controlled triggering of mast cells using atomic force microscopy|url=https://doi.org/10.1007/s12026-014-8510-7|journal=Immunologic Research|language=en|volume=58|issue=2|pages=211–217|doi=10.1007/s12026-014-8510-7|issn=1559-0755|pmc =  4154250|pmid=24777418}}</ref>


== See also ==
== See also ==

Latest revision as of 15:18, April 3, 2023

Neural strain from biomechanical stress can cause profound metabolic changes in the affected tissue due to alterations in the morphology of the cell membrane and decreased blood flow[1][2][3][4][5][6][7] causing hypoxia. Injury can result from tensile, compressive, or shear stress or as a combination of stresses.[1] Metabolic changes include a shift to anaerobic metabolism, resulting in increased lactate dehydrogenase[8] and reduced ATP production,[9] and changes in electrolyte balance, including an increase in intracellular calcium in a dose-dependent manner.[10][11][8]

Tension[edit | edit source]

In animal models, stretching or tension of nerves results in substantially reduced blood flow.[1][2][3][4][5][6][7][12] Tension impairs nerve regeneration.[13]

Tethered cord syndrome[edit | edit source]

Tethered cord syndrome, a condition where tissue attachments limit the movement of the spinal cord within the spinal column, is associated with impaired glucose metabolism in spinal cord tissue,[14] changes in the reduction/oxidation ratio of cytochrome oxidase.[15] and reduced ATP production.[9] People with tethered cord syndrome have reduced blood flow to the spinal cord.[16]

A study of energy cost of walking in adolescents with tethered cord, as measured by oxygen uptake (VO2), found that “energy cost per metre during walking at preferred speed and physical strain were higher than in peers without disability.”[17]

“Traction on the caudal cord results in decreased blood flow causing metabolic derangements that culminate in motor, sensory, and urinary neurological deficits. The untethering operation restores blood flow and reverses the clinical picture in most symptomatic cases.”[18]

In a study of five children undergoing surgery for tethered cord syndrome group, spinal cord blood flow prior to untethering was a mean of 12.6 ml/min per 100 g of tissue. It increased in all cases after release to a mean of 29.4 ml/min per 100 g of tissue.[19]

Compression[edit | edit source]

Compression of nerves can result in low blood flow;[20] changes in microcirculation and ischemia;[21] changes in vascular permeability, edema,[22] axonal damage; and has been associated with demyelination.[1][23][24][25]

Prologned compression can result in inflammation and activation of endoneurial fibroblasts, mast cells, and macrophages.[26]

Diagnoses[edit | edit source]

Diagnoses associated with tension, compressive and shear stress:

ME/CFS[edit | edit source]

In a study of neuromuscular strain in ME/CFS, 60 people with ME/CFS and 20 healthy controls randomly were assigned to undergo a neuromuscular strain maneuver (“straight leg test”) or sham maneuver. Those with ME/CFS in the strain condition group had significantly increased symptoms for up to 24 hours.[27]

Mast cell activation syndrome[edit | edit source]

Mast cells are distributed throughout the nervous system, including in the dura, and are known to degranulate when nervous tissue is stretched.[28][29]

See also[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 Boyd, Benjamin S.; Topp, Kimberly S. (January 1, 2006). "Structure and Biomechanics of Peripheral Nerves: Nerve Responses to Physical Stresses and Implications for Physical Therapist Practice". Physical Therapy. 86 (1): 92–109. doi:10.1093/ptj/86.1.92. ISSN 0031-9023.
  2. 2.0 2.1 Clark, William L.; Trumble, Thomas E.; Swiontkowski, Mark F.; Tencer, Allan F. (July 1, 1992). "Nerve tension and blood flow in a rat model of immediate and delayed repairs". The Journal of Hand Surgery. 17 (4): 677–687. doi:10.1016/0363-5023(92)90316-H. ISSN 0363-5023.
  3. 3.0 3.1 Clark, William L.; Trumble, Thomas E.; Swiontkowski, Mark F.; Tencer, Allan F. (July 1, 1992). "Nerve tension and blood flow in a rat model of immediate and delayed repairs". The Journal of Hand Surgery. 17 (4): 677–687. doi:10.1016/0363-5023(92)90316-H. ISSN 0363-5023.
  4. 4.0 4.1 Driscoll, Peter J.; Glasby, Michael A.; Lawson, Graham M. (2002). "An in vivo study of peripheral nerves in continuity: biomechanical and physiological responses to elongation". Journal of Orthopaedic Research. 20 (2): 370–375. doi:10.1016/S0736-0266(01)00104-8. ISSN 1554-527X.
  5. 5.0 5.1 Tanoue, M.; Yamaga, M.; Ide, J.; Takagi, K. (June 1996). "Acute stretching of peripheral nerves inhibits retrograde axonal transport". Journal of Hand Surgery (Edinburgh, Scotland). 21 (3): 358–363. ISSN 0266-7681. PMID 8771477.
  6. 6.0 6.1 Ogata, K.; Naito, M. (February 1986). "Blood flow of peripheral nerve effects of dissection, stretching and compression". Journal of Hand Surgery (Edinburgh, Scotland). 11 (1): 10–14. ISSN 0266-7681. PMID 3958526.
  7. 7.0 7.1 Jou, I.M.; Lai, K.A.; Shen, C.L.; Yamano, Y. (January 2000). "Changes in conduction, blood flow, histology, and neurological status following acute nerve-stretch injury induced by femoral lengthening". Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society. 18 (1): 149–155. doi:10.1002/jor.1100180121. ISSN 0736-0266. PMID 10716291.
  8. 8.0 8.1 Laplaca, Michelle C.; Lee, Virginia M.-Y.; Thibault, Lawrence E. (June 1, 1997). "An In Vitro Model of Traumatic Neuronal Injury: Loading Rate-Dependent Changes in Acute Cytosolic Calcium and Lactate Dehydrogenase Release". Journal of Neurotrauma. 14 (6): 355–368. doi:10.1089/neu.1997.14.355. ISSN 0897-7151.
  9. 9.0 9.1 Sullivan, Stephen; Park, Paul; Stetler, William R. (July 1, 2010). "Pathophysiology of adult tethered cord syndrome: review of the literature". Neurosurgical Focus. 29 (1): E2. doi:10.3171/2010.3.FOCUS1080. ISSN 1092-0684.
  10. Cargill, Robert S.; Geddes, Donna M. (June 1, 2001). "An in Vitro Model of Neural Trauma: Device Characterization and Calcium Response to Mechanical Stretch". Journal of Biomechanical Engineering. 123 (3): 247–255. doi:10.1115/1.1374201. ISSN 0148-0731.
  11. Cargill, Robert S.; Thibault, Lawrence E. (July 1, 1996). "Acute Alterations in [Ca2+]i in NG108-15 Cells Subjected to High Strain Rate Deformation and Chemical Hypoxia: An in Vitro Model for Neural Trauma". Journal of Neurotrauma. 13 (7): 395–407. doi:10.1089/neu.1996.13.395. ISSN 0897-7151.
  12. Ogata, Kosuke; Naito, Masatoshi (February 1, 1986). "Blood flow of peripheral nerve effects of dissection stretching and compression". The Journal of Hand Surgery: British & European Volume. 11 (1): 10–14. doi:10.1016/0266-7681(86)90003-3. ISSN 0266-7681.
  13. Sunderland, Ian R.P.; Brenner, Michael J.; Singham, Janakie; Rickman, Susan R.; Hunter, Daniel A.; Mackinnon, Susan E. (October 2004). "Effect of Tension on Nerve Regeneration in Rat Sciatic Nerve Transection Model". Annals of Plastic Surgery. 53 (4): 382. doi:10.1097/01.sap.0000125502.63302.47. ISSN 0148-7043.
  14. Colohan, Austin R.T.; Zouros, Alexander; Siddiqi, Javed; Yamada, Shoko M.; Yamada, Brian S.; Pezeshkpour, Gholam; Won, Daniel J.; Yamada, Shokei (August 1, 2007). "Pathophysiology of tethered cord syndrome and similar complex disorders". Neurosurgical Focus. 23 (2): 1–10. doi:10.3171/FOC-07/08/E6. ISSN 1092-0684.
  15. Yamada, Shoko M.; Won, Daniel J.; Yamada, Shokei (February 1, 2004). "Pathophysiology of tethered cord syndrome: correlation with symptomatology". Neurosurgical Focus. 16 (2): 1–5. doi:10.3171/foc.2004.16.2.7. ISSN 1092-0684.
  16. Colohan, Austin R.T.; Zouros, Alexander; Siddiqi, Javed; Yamada, Shoko M.; Yamada, Brian S.; Pezeshkpour, Gholam; Won, Daniel J.; Yamada, Shokei (August 1, 2007). "Pathophysiology of tethered cord syndrome and similar complex disorders". Neurosurgical Focus. 23 (2): 1–10. doi:10.3171/FOC-07/08/E6. ISSN 1092-0684.
  17. Bruinings, A.L.; Berg‐Emons, H. J. G. Van Den; Buffart, L.M.; Heijden‐Maessen, H. C.M. Van Der; Roebroeck, M.E.; Stam, H.J. (2007). "Energy cost and physical strain of daily activities in adolescents and young adults with myelomeningocele". Developmental Medicine & Child Neurology. 49 (9): 672–677. doi:10.1111/j.1469-8749.2007.00672.x. ISSN 1469-8749.
  18. Rekate, Harold L.; Theodore, Nicholas; Kalani, M. Yashar; Filippidis, Aristotelis S. (July 1, 2010). "Spinal cord traction, vascular compromise, hypoxia, and metabolic derangements in the pathophysiology of tethered cord syndrome". Neurosurgical Focus. 29 (1): E9. doi:10.3171/2010.3.FOCUS1085. ISSN 1092-0684.
  19. Danto, Joseph; Greenberg, Burt M.; Rosenthal, Alan D.; Schneider, Steven J. (February 1, 1993). "A Preliminary Report on the Use of Laser-Doppler Flowmetry during Tethered Spinal Cord Release". Neurosurgery. 32 (2): 214–218. doi:10.1227/00006123-199302000-00010. ISSN 0148-396X.
  20. Rydevik, B.; Lundborg, G.; Bagge, U. (January 1, 1981). "Effects of graded compression on intraneural blood flow: An in vivo study on rabbit tibial nerve". The Journal of Hand Surgery. 6 (1): 3–12. doi:10.1016/S0363-5023(81)80003-2. ISSN 0363-5023.
  21. Rydevik, B.; Lundborg, G.; Bagge, U. (January 1, 1981). "Effects of graded compression on intraneural blood flow: An in vivo study on rabbit tibial nerve". The Journal of Hand Surgery. 6 (1): 3–12. doi:10.1016/S0363-5023(81)80003-2. ISSN 0363-5023.
  22. Powell, H.; Myers, R.; Lundborg, G. (December 1, 1983). "Nerve compression injury and increased endoneurial fluid pressure: a "miniature compartment syndrome"". Journal of Neurology, Neurosurgery & Psychiatry. 46 (12): 1119–1124. doi:10.1136/jnnp.46.12.1119. ISSN 0022-3050. PMID 6663311.
  23. Myers, R.R.; Powell, H.C. (July 1986). "Pathology of experimental nerve compression". Laboratory investigation; a journal of technical methods and pathology. 55 (1): 91–100. ISSN 0023-6837. PMID 3724067.
  24. Dahlin, L.B.; Lundborg, G. (June 1992). "The pathophysiology of nerve compression". Hand clinics. 8 (2): 215–227. ISSN 0749-0712. PMID 1613031.
  25. Dahlin, L.B.; Lundborg, G. (May 1996). "Anatomy, function, and pathophysiology of peripheral nerves and nerve compression". Hand clinics. 12 (2): 185–193. ISSN 0749-0712. PMID 8724572.
  26. Powell, H.C.; Myers, R.R. (July 1986). "Pathology of experimental nerve compression". Laboratory Investigation; a Journal of Technical Methods and Pathology. 55 (1): 91–100. ISSN 0023-6837. PMID 3724067.
  27. Violand, Richard L.; Thompson, Carol B.; Moni, Malini; Marden, Colleen L.; Jasion, Samantha E.; Lauver, Megan; Fontaine, Kevin R.; Rowe, Peter C. (July 18, 2016). "Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome". PLOS ONE. 11 (7): e0159386. doi:10.1371/journal.pone.0159386. ISSN 1932-6203.
  28. Skaper, Stephen D.; Facci, Laura; Giusti, Pietro (March 2014). "Mast cells, glia and neuroinflammation: partners in crime?". Immunology. 141 (3): 314–327. doi:10.1111/imm.12170. ISSN 1365-2567. PMC 3930370. PMID 24032675.
  29. Hu, Kenneth K.; Bruce, Marc A.; Butte, Manish J. (May 1, 2014). "Spatiotemporally and mechanically controlled triggering of mast cells using atomic force microscopy". Immunologic Research. 58 (2): 211–217. doi:10.1007/s12026-014-8510-7. ISSN 1559-0755. PMC 4154250. PMID 24777418.