Persistent restoration of sensory function by immediate or delayed systemic artemin after dorsal root injury.
Dorsal root injury results in substantial and often irreversible loss of sensory functions as a result of the limited regenerative capacity of sensory axons and the inhibitory barriers that prevent both axonal entry into and regeneration in the spinal cord. Here, we describe previously unknown effects of the growth factor artemin after crush injury of the dorsal spinal nerve roots in rats. Artemin not only promoted re-entry of multiple classes of sensory fibers into the spinal cord and re-establishment of synaptic function and simple behavior, but it also, surprisingly, promoted the recovery of complex behavior. These effects occurred after a 2-week schedule of intermittent, systemic administration of artemin and persisted for at least 6 months following treatment, suggesting a substantial translational advantage. Systemic artemin administration produced essentially complete and persistent restoration of nociceptive and sensorimotor functions, and could represent a promising therapy that may effectively promote sensory neuronal regeneration and functional recovery after injury.
Wang
Ruizhong
R
Department of Pharmacology, University of Arizona, College of Medicine, 1501 N Campbell Avenue, Tucson, Arizona 85724-5050, USA.
King
Tamara
T
Ossipov
Michael H
MH
Rossomando
Anthony J
AJ
Vanderah
Todd W
TW
Harvey
Pamela
P
Cariani
Peter
P
Frank
Eric
E
Sah
Dinah W Y
DW
Porreca
Frank
F
D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D008297:Male; D009408:Nerve Compression Syndromes / Q000188:drug therapy / Q000517:prevention & control*; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D013997:Time Factors
C490887:Artn protein, rat; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins