Open AccessProgranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice
Author(s) -
Lim HeeYoung,
Albuquerque Boris,
Häussler Annett,
Myrczek Thekla,
Ding Aihao,
Tegeder Irmgard
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01350.x
Subject(s) - neuropathic pain , nerve injury , medicine , sciatic nerve , nociception , neurite , sciatic nerve injury , microglia , haploinsufficiency , neuroscience , peripheral nerve injury , chronic pain , anesthesia , inflammation , biology , phenotype , biochemistry , receptor , psychiatry , gene , in vitro
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.