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Hydrogels delivered \u223c98% 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 (<jats:italic>n<\/jats:italic>\u2009=\u20096\/group) was significantly decreased with GDNF delivered by the hydrogel compared to the three injury control groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.03). The bolus GDNF treatment did not reduce allodynia at any time point. The GDNF receptor (GFR\u03b1\u20101) 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 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). These data suggest efficacy for degradable hydrogel delivery of GDNF and support this treatment approach for nerve root\u2010mediated pain. \u00a9 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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