Neurotrophins: Peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity

Brain-derived neurotrophic factor (BDNF) is expressed in nociceptive sensor y neurons and transported anterogradely to the dorsal horn of the spinal co rd where it is located in dense core,vesicles in C-fiber terminals. Periphe ral inflammation substantially up-regulates BDNF mRNA and protein in the do rsal root ganglion (DRG) in a nerve growth factor-dependent fashion and res ults in novel expression of BDNF by DRG neurons with myelinated axons. C-fi ber electrical activity also increases BDNF expression in the DRG, and both inflammation and activity increase full-length TrkB receptor levels in the dorsal horn, Sequestration of endogenous BDNF/neurotrophin 4 by intraspina l TrkB-Fc fusion protein administration does not, in noninflamed animals, c hange basal pain sensitivity nor the mechanical hypersensitivity induced by peripheral capsaicin administration, a measure of C fiber-mediated central sensitization. TrkB-Fc administration also does not modify basal inflammat ory pain hypersensitivity, but does block the progressive hypersensitivity elicited by low-intensity tactile stimulation of inflamed tissue. BDNF, by virtue of its nerve growth factor regulation in sensory neurons including n ovel expression in A fibers, has a role as a central modulator of tactile s timulus-induced inflammatory pain hypersensitivity.