RT Journal Article
SR Electronic
T1 Alleviation of Neuropathic Pain Hypersensitivity by Inhibiting Neuronal Pentraxin 1 in the Rostral Ventromedial Medulla
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12431
OP 12436
DO 10.1523/JNEUROSCI.2730-12.2012
VO 32
IS 36
A1 Agustin Zapata
A1 Silvia Pontis
A1 Raf J. Schepers
A1 Ruizhong Wang
A1 Eric Oh
A1 Alexandra Stein
A1 Cristina M. Bäckman
A1 Paul Worley
A1 Marta Enguita
A1 M. Alba Abad
A1 Ramon Trullas
A1 Toni S. Shippenberg
YR 2012
UL http://www.jneurosci.org/content/32/36/12431.abstract
AB Peripheral nerve injury causes spontaneous and long-lasting pain, hyperalgesia, and allodynia. Excitatory amino acid receptor-dependent increases in descending facilitatory drive from the brainstem rostral ventromedial medulla (RVM) contribute to injury-evoked hypersensitivity. Although increased excitability likely reflects changes in synaptic efficacy, the cellular mechanisms underlying injury-induced synaptic plasticity are poorly understood. Neuronal pentraxin 1 (NP1), a protein with exclusive CNS expression, is implicated in synaptogenesis and AMPA receptor recruitment to immature synapses. Its role in the adult brain and in descending pain facilitation is unknown. Here, we use the spared nerve injury (SNI) model in rodents to examine this issue. We show that SNI increases RVM NP1 expression and constitutive deletion or silencing NP1 in the RVM, before or after SNI, attenuates allodynia and hyperalgesia in rats. Selective rescue of RVM NP1 expression restores behavioral hypersensitivity of knock-out mice, demonstrating a key role of RVM NP1 in the pathogenesis of neuropathic pain.