Fibronectin inhibits chronic pain development after spinal cord injury.
Chronic pain following spinal cord injury (SCI) is a highly prevalent clinical condition that is difficult to treat. Using both von Frey filaments and radiant infrared heat to assess mechanical allodynia and thermal hyperalgesia, respectively, we have demonstrated that a one-time injection of fibronectin (50 μg/mL) into the spinal dorsal column (1 μL/min each injection for a total of 5 μL) immediately after SCI inhibits the development of mechanical allodynia (but not thermal hyperalgesia) over an 8-month observation period following spinal cord dorsal column crush (DCC). DCC will only induce mechanical Allodynia, but not thermal hyperalgesia or overt motor deficits. By applying various fibronectin fragments as well as competitive inhibitors, these effects were shown to be dependent on the connecting segment-1 (CS-1) motif of fibronectin. Furthermore, we found that acute fibronectin treatment diminished inflammation and blood-spinal cord barrier permeability, which in turn leads to enhanced fiber sparing and sprouting. In particular, the reduction of serotonin (5-HT) in the superficial dorsal horn, an important descending brainstem system in the modulation of pain, was blocked with fibronectin treatment. We conclude that treatment of SCI with fibronectin preserves sensory regulation and prevents the development of chronic allodynia, providing a potential therapeutic intervention to treat chronic pain following SCI.
Department of Neuroscience, Lerner Research Institute, Cleveland, Ohio 44195, USA. linc@ccf.org
Ching-Yi
CY
Lin
Yu-Shang
YS
Lee
Vernon W
VW
Lin
Jerry
J
Silver
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D059350:Chronic Pain / Q000209:etiology* / Q000517:prevention & control*; D005353:Fibronectins / Q000494:pharmacology*; D006614:Hindlimb / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications*
D005353:Fibronectins; D012701:Serotonin