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Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that is upregulated following peripheral nerve injury. Following synthesis in small- to medium-sized dorsal root ganglion (DRG) neurones,BDNF is anterogradely transported to the dorsal horn where released upon noxious stimulation in an activity-dependent manner. The physiological actions of BDNF are mediated via interaction with two receptors, the high affinity tyrosine receptor kinase B (TrkB) and p75NTR, also known as low-affinity nerve growth factor receptor (LNGFR). BDNF engagement of TrkB results in receptor dimerization, leading to autophosphorylation of tyrosine residues in the cytoplasmic domain. Agents that specifically recognize BDNF, and inhibit BDNF signaling through its receptor, may provide a novel approach for the treatment of certain chronic pain conditions. However, a key consideration in the design of a potential therapeutic is the restriction of drug access to the brain to ensure there is minimal interference of BDNF function in the CNS.