Neurotrophic factors, such as nerve growth factorand brain-derived neurotrophic factor, are members of thestructurally related neurotrophin family that play importantroles in pain modulation. Although there are also indicationsfor the involvement of glial cell line-derived neurotrophicfactor (GDNF), it is unclear whether and how GDNF is involvedin inflammatory pain. In the present study, we studiedthe expression pattern of GDNF in dorsal root ganglia (DRG)and spinal cord, using confocal microscopy. We demonstratethat GDNF is well associated with nonpeptidergic pain pathwayand that GDNF could possibly be anterogradely transportedfrom DRG neurons to superficial spinal cord dorsalhorn. We also studied the dynamic changes of GDNF expressionin rats during chronic inflammation using injection ofcomplete Freund's adjuvant as a model of chronic pain. Wefound that GDNF was down-regulated in both dorsal rootganglia and spinal cords 2 weeks after arthritis induction. Toassess the impact of this down-regulation on pain transmission,we used a function-blocking antibody against GDNFdelivered intrathecally in the same chronic-pain animal models.Injection of this antibody to GDNF produced no immediateeffect, but decreased the delayed, bilateral hyperalgesiainduced from a unilateral injection of complete Freund’s adjuvant.The effect of this antibody coincided with the downregulationof GDNF immunoreactivity in response to inflammation,suggesting that GDNF supports biochemicalchanges that contribute to hyperalgesia. © 2003 IBRO. Publishedby Elsevier Science Ltd. All rights reserved.