Multiple actions of systemic artemin in experimental neuropathy.
The clinical management of neuropathic pain is particularly challenging. Current therapies for neuropathic pain modulate nerve impulse propagation or synaptic transmission; these therapies are of limited benefit and have undesirable side effects. Injuries to peripheral nerves result in a host of pathophysiological changes associated with the sustained expression of abnormal pain. Here we show that systemic, intermittent administration of artemin produces dose- and time-related reversal of nerve injury-induced pain behavior, together with partial to complete normalization of multiple morphological and neurochemical features of the injury state. These effects of artemin were sustained for at least 28 days. Higher doses of artemin than those completely reversing experimental neuropathic pain did not elicit sensory or motor abnormalities. Our results indicate that the behavioral symptoms of neuropathic pain states can be treated successfully, and that partial to complete reversal of associated morphological and neurochemical changes is achievable with artemin.
Gardell
Luis R
LR
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA.
Wang
Ruizhong
R
Ehrenfels
Chris
C
Ossipov
Michael H
MH
Rossomando
Anthony J
AJ
Miller
Stephan
S
Buckley
Carolyn
C
Cai
Amber K
AK
Tse
Albert
A
Foley
Susan F
SF
Gong
BangJian
B
Walus
Lee
L
Carmillo
Paul
P
Worley
Dane
D
Huang
Carol
C
Engber
Thomas
T
Pepinsky
Blake
B
Cate
Richard L
RL
Vanderah
Todd W
TW
Lai
Josephine
J
Sah
Dinah W Y
DW
Porreca
Frank
F
D000818:Animals; D015415:Biomarkers; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects; D004399:Dynorphins / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries*
C490887:Artn protein, rat; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D004399:Dynorphins; D015740:Calcitonin Gene-Related Peptide