TY  - JOUR
A1  - Lim, Hee-Young
A1  - Albuquerque, Boris
A1  - Häussler, Annett
A1  - Myrczek, Thekla
A1  - Ding, Aihao
A1  - Tegeder, Irmgard
T1  - Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice
T2  - Journal of cellular and molecular medicine
N2  - Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up-regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain-like behaviour and delayed the recovery of motor functions. Compared to wild-type mice, progranulin-deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up-regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury-associated chronic pain.
KW  - nerve injury
KW  - growth factor
KW  - microglia
KW  - neuroinflammation
KW  - pain, dorsal root ganglia
KW  - spinal cord
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28626
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-286266
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822842/
SN  - 1582-4934
SN  - 1582-1838
N1  - © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an Open Access article under the terms of the Creative Commons Attribution Non Commercial License http://creativecommons.org/licenses/by-nc/3.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
VL  - 16
IS  - 4
SP  - 708
EP  - 721
PB  - Wiley-Blackwell
CY  - Hoboken, NJ
ER  -