Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity.
Brain-derived neurotrophic factor (BDNF) is expressed in nociceptive sensory neurons and transported anterogradely to the dorsal horn of the spinal cord where it is located in dense core vesicles in C-fiber terminals. Peripheral inflammation substantially up-regulates BDNF mRNA and protein in the dorsal root ganglion (DRG) in a nerve growth factor-dependent fashion and results in novel expression of BDNF by DRG neurons with myelinated axons. C-fiber 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 intraspinal TrkB-Fc fusion protein administration does not, in noninflamed animals, change 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 inflammatory 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 novel expression in A fibers, has a role as a central modulator of tactile stimulus-induced inflammatory pain hypersensitivity.
Mannion
R J
RJ
Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Costigan
M
M
Decosterd
I
I
Amaya
F
F
Ma
Q P
QP
Holstege
J C
JC
Ji
R R
RR
Acheson
A
A
Lindsay
R M
RM
Wilkinson
G A
GA
Woolf
C J
CJ
D000818:Animals; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003655:Decerebrate State; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000502:physiology / Q000503:physiopathology; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology* / Q000503:physiopathology; D013997:Time Factors; D014110:Touch; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases