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Neurotrophic factors, which support neuronal survival and growth during development of the nervous system, have been shown to play significant roles in the transmission of physiologic and pathologic pain. Brain-derived neurotrophic factor (BDNF), synthesized in the primary sensory neurons, is anterogradely transported to the central terminals of the primary afferents in the spinal dorsal horn, where it is involved in the modulation of painful stimuli. In models of inflammatory and neuropathic pain, BDNF synthesis is greatly increased in different populations of dorsal root ganglion (DRG) neurons. Furthermore, it is now known that the activation of mitogen-activated protein kinases occurs in these sensory neurons and contributes to persistent inflammatory and neuropathic pain by regulating BDNF expression. The recent discovery that BDNF upregulation in the DRG and spinal cord contributes to chronic pain hypersensitivity indicates that blocking BDNF in sensory neurons could provide a fruitful strategy for the development of novel analgesics.