Controlled release of GDNF reduces nerve root-mediated behavioral hypersensitivity.
Nerve root compression produces persistent behavioral sensitivity in models of painful neck injury. This study utilized degradable poly(ethylene glycol) hydrogels to deliver glial cell line-derived neurotrophic factor (GDNF) to an injured nerve root. Hydrogels delivered approximately 98% of encapsulated GDNF over 7 days in an in vitro release assay without the presence of neurons and produced enhanced outgrowth of processes in cortical neural cell primary cultures. The efficacy of a GDNF hydrogel placed on the root immediately after injury was assessed in a rat pain model of C7 dorsal root compression. Control groups included painful injury followed by: (1) vehicle hydrogel treatment (no GDNF), (2) a bolus injection of GDNF, or (3) no treatment. After injury, mechanical allodynia (n = 6/group) was significantly decreased with GDNF delivered by the hydrogel compared to the three injury control groups (p < 0.03). The bolus GDNF treatment did not reduce allodynia at any time point. The GDNF receptor (GFRalpha-1) decreased in small, nociceptive neurons of the affected dorsal root ganglion, suggesting a decrease in receptor expression following injury. GDNF receptor immunoreactivity was significantly greater in these neurons following GDNF hydrogel treatment relative to GDNF bolus treated and untreated rats (p < 0.05). These data suggest efficacy for degradable hydrogel delivery of GDNF and support this treatment approach for nerve root-mediated pain.
Hubbard
Raymond D
RD
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321, USA.
Martínez
Joan J
JJ
Burdick
Jason A
JA
Winkelstein
Beth A
BA
D000818:Animals; D001522:Behavior, Animal; D001681:Biological Assay; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical; D013997:Time Factors
D051100:Glial Cell Line-Derived Neurotrophic Factor; D020100:Hydrogels; D009414:Nerve Growth Factors; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate