Pathophysiology and Related Studies of the No Reflow Phenomenon in Skeletal Muscle

Allen, Diane M.; Chen, Long‐En; Seaber, Anthony V.; Urbaniak, James R.

doi:10.1097/00003086-199505000-00016

Cited by 33 publications

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Section: Discussionmentioning

confidence: 99%

“…The temporal reduction in effectiveness may depend partly on a shift in the reliance of persistent ischemia on arterial vasospasms to no-reflow, a phenomenon that develops quickly after prolonged ischemia or repeated I-R injury. 2,38,49 In CRPS-I patients, a slower development of no-reflow may also result in chronic tissue ischemia and pain that is more resistant to relief by sympathetic blockers.In conclusion, CPIP rats show evidence of SMP (as defined clinically), since their mechanical allodynia is relieved by both sympathetic block and systemic phentolamine treatment. Furthermore, the responses to prazosin, clonidine, and the nitric oxide donor SIN-1 demonstrates that pain relief in CPIP rats can be produced by agents that decrease sympathetic vasoconstriction or enhance vasodilatation.…”

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confidence: 99%

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Sympathetic Vasoconstrictor Antagonism and Vasodilatation Relieve Mechanical Allodynia in Rats With Chronic Postischemia Pain

Xanthos

Coderre

2008

The Journal of Pain

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Chronic pain that responds to antisympathetic treatments and α-adrenergic antagonists is clinically referred to as sympathetically maintained pain. Animal models of neuropathic pain have shown mixed results in terms of antinociceptive effectiveness of antisympathetic agents. The effectiveness of these agents have not been yet investigated in animal models of complex regional pain syndrome-type 1 (CRPS-I). In this study, we examined the effectiveness of antisympathetic agents and sympathetic vasoconstrictor antagonists, as well as agents that are vasodilators, in relieving mechanical allodynia in a recently developed animal model of CRPS-I (chronic postischemia pain or CPIP) produced by three hours of hind paw ischemia-reperfusion injury. Systemic guanethidine, phentolamine, clonidine, and prazosin are effective in reducing mechanical allodynia particularly at 2 days after reperfusion, and less so at 7 days after reperfusion. A nitric oxide donor vasodilator, SIN-1, also reduces mechanical allodynia more effectively at 2 days after reperfusion, but not at 7 days after reperfusion. These results suggest that the pain of CPIP, and possibly also CRPS-I, is relieved by reducing sympathetically mediated vasoconstriction, or enhancing vasodilatation. KeywordsComplex regional pain syndrome; ischemia-reperfusion injury; neuropathic pain; allodynia; sympathetic block; adrenergic receptors Complex regional pain syndrome-type I (CRPS-I) is a disorder that occurs after fracture, soft tissue or crush injury. 16 Symptoms of CRPS-I include spontaneous burning (cutaneous) and aching (deep) pain, hyperalgesia, allodynia, and disorders of vasomotor and sudomotor regulation. 27,57 CRPS-II is similar but also exhibits a clinically verified nerve injury. CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptAlthough controversial, sympathetic blocks are often reported to relieve CRPS pain. 10,29,68 CRPS pain is also relieved with α-adrenergic antagonists such as phentolamine or phenoxybenzamine, 48,52 agents that have been used as diagnostic tools for identifying socalled sympathetically maintained pain (SMP We recently introduced chronic postischemia pain (CPIP) as an animal model of CRPS-I produced after hind paw ischemia-reperfusion (I-R) injury.14 This animal model shows signs of I-R injury such as no-reflow and vascular abnormalities, as well as nociceptive and vascular hypersensitivity to norepinephrine. 38,78 The pain-relieving effects of antisympathetic agents have not previously been tested in animal models of CRPS-I. 21,22,71 In this report, we examine whether antisympathetic drugs, and agents that are vasodilators, are effective in reducing painful symptoms in this model. Thus, we test the effectiveness of sympathetic block with guanethidine, or systemic treatments with the α1-and α2-adrenergic antagonists prazosin and yohimbine, the α2-adrenergic agonist clonidine, and a nitric oxide donor, in relieving mechanical allodynia in CPIP rats at 2 and 7 days after reperfusion. Materials and Methods Animal...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Sympathetic Vasoconstrictor Antagonism and Vasodilatation Relieve Mechanical Allodynia in Rats With Chronic Postischemia Pain

Xanthos

Coderre

2008

The Journal of Pain

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“…Early derangements of calcium regulation may also contribute. 45,46 Alternatively, NO production from eNOS, which is upregulated during early reperfusion, may preserve blood flow more so than contractility. 47 The finding that 1400W treatment significantly reduced iNOS gene expression to a quarter and protein expression to half of that seen in controls after 3-h reperfusion, but had no significant effect on the expression of nNOS and eNOS protein and eNOS mRNA when compared to controls (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle

Patel

Allen

et al. 2004

Microsurgery

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This study examined the effects of 1400W, an inhibitor of inducible nitric oxide (iNOS), on contractile function and iNOS expression in reperfused skeletal muscle. The right extensor digitorum longus (EDL) muscle of 104 rats underwent a sham operation or 3-h ischemia followed by 3-h or 24-h reperfusion (I/R). Rats received 3 mg/kg 1400W, 10 mg/kg 1400W, or water subcutaneously. Results showed that EDL contractile function in both 1400W-treated groups significantly outperformed the controls at 24-h but not at 3-h reperfusion. Although iNOS expression increased in all three I/R groups during reperfusion, a significantly smaller increase was found in 1400W-treated muscles after 3-h reperfusion, and more dramatically so after 24-h reperfusion. Our results indicate that inhibition of iNOS preserved the contractile function in reperfused skeletal muscle, perhaps via downregulating iNOS expression. Protection by 1400W at 24-h reperfusion suggests that the role of iNOS in exaggerating reperfusion injury is more prominent in the later stages of injury.

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“…The existence of this phenomenon was confirmed in a variety of animal models of brain ischemia. [3][4][5][6] It was also shown in a variety of other organs, including skin, 7,8 skeletal muscle, 9 and the kidney. 10 -12 Kloner et al 13 sought to find out whether the no-reflow phenomenon would be observed in ischemic canine hearts and whether it was related to microvascular damage.…”

Section: Historical Perspectivementioning

confidence: 99%

No-Reflow Phenomenon

2002

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Pathophysiology and Related Studies of the No Reflow Phenomenon in Skeletal Muscle

Cited by 33 publications

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Sympathetic Vasoconstrictor Antagonism and Vasodilatation Relieve Mechanical Allodynia in Rats With Chronic Postischemia Pain

Sympathetic Vasoconstrictor Antagonism and Vasodilatation Relieve Mechanical Allodynia in Rats With Chronic Postischemia Pain

Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle

No-Reflow Phenomenon

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