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. 2011 Dec;32(36):9738-46.
doi: 10.1016/j.biomaterials.2011.09.021. Epub 2011 Sep 22.

The Potential for Salmon Fibrin and Thrombin to Mitigate Pain Subsequent to Cervical Nerve Root Injury

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Free PMC article

The Potential for Salmon Fibrin and Thrombin to Mitigate Pain Subsequent to Cervical Nerve Root Injury

Christine L Weisshaar et al. Biomaterials. .
Free PMC article

Abstract

Nerve root compression is a common cause of radiculopathy and induces persistent pain. Mammalian fibrin is used clinically as a coagulant but presents a variety of risks. Fish fibrin is a potential biomaterial for neural injury treatment because it promotes neurite outgrowth, is non-toxic, and clots readily at lower temperatures. This study administered salmon fibrin and thrombin following nerve root compression and measured behavioral sensitivity and glial activation in a rat pain model. Fibrin and thrombin each significantly reduced mechanical allodynia compared to injury alone (p < 0.02). Painful compression with fibrin exhibited allodynia that was not different from sham for any day using stimulation by a 2 g filament; allodynia was only significantly different (p < 0.043) from sham using the 4 g filament on days 1 and 3. By day 5, responses for fibrin treatment decreased to sham levels. Allodynia following compression with thrombin treatment were unchanged from sham at any time point. Macrophage infiltration at the nerve root and spinal microglial activation were only mildly modified by salmon treatments. Spinal astrocytic expression decreased significantly with fibrin (p < 0.0001) but was unchanged from injury responses for thrombin treatment. Results suggest that salmon fibrin and thrombin may be suitable biomaterials to mitigate pain.

Figures

Figure 1
Figure 1
Mechanical allodynia in the ipsilateral forepaw for injury, NB media, fibrin, thrombin, and sham for testing with the 2 g and 4 g von Frey filaments. Injury significantly increased the number of paw withdrawals relative to sham (#p<0.001) for testing with both filaments. Responses following treatment with fibrin were significantly reduced relative to injury (*p<0.02) for both filaments. Fibrin responses were not different from sham for any day of testing with the 2 g filament, and were only different on days 1 and 3 (‡p<0.043) using the 4 g filament. Treatment with thrombin significantly reduced allodynia compared to injury (φp<0.02) for testing with both filaments. Thrombin and sham responses were not different at any day for either filament. Data shown as average±standard deviation.
Figure 2
Figure 2
Representative images of ED1 immunostaining at the C7 nerve root at day 7. Intense macrophage infiltration was observed in the nerve root after (A) injury, but roots that had treatment with (B) fibrin or (C) thrombin displayed only mild reactivity. (D) NB media treatment and (E) sham procedures resulted in little-to-no ED1 staining. Scale bar shown is 50 μm and applies to all.
Figure 3
Figure 3
Representative C6 spinal cord sections on the side ipsilateral to the nerve root compression showing staining against GFAP (A–E) and Iba1 (F–J) at day 7 for injury, fibrin, thrombin, NB media, and sham. GFAP expression increased following injury and thrombin procedures; Iba1 expression was not significantly different between any group. Scale bar shown is 50 μm and applies to all.
Figure 4
Figure 4
Automated densitometry quantifying the percentage of positive pixels in the spinal cord reactive for (A) GFAP and (B) Iba1 staining at day 7. GFAP reactivity increased following injury relative to fibrin (p<0.0001) and NB media (p<0.027). Injury with thrombin treatment also exhibited increased GFAP reactivity compared to fibrin (p<0.0001), NB media (p<0.0001) and sham (p<0.002). Iba1 expression was elevated after injury and decreased with treatment of fibrin, thrombin, NB media, and for sham procedures, but was not significant. Asterisk (*) indicates a significant increase over fibrin, plus sign (+) indicates a significant increase over NB media, and pound sign (#) indicates a significant increase over sham. Data shown as average±standard deviation.

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