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 similar to 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 (GFR alpha-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 bolustreated 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. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:120-127, 2009