TY - JOUR
T1 - Alleviation of neuropathic pain hypersensitivity by inhibiting Neuronal pentraxin 1 in the rostral ventromedial medulla
AU - Zapata, Agustin
AU - Pontis, Silvia
AU - Schepers, Raf J.
AU - Wang, Ruizhong
AU - Oh, Eric
AU - Stein, Alexandra
AU - Bäckman, Cristina M.
AU - Worley, Paul
AU - Enguita, Marta
AU - Alba Abad, M.
AU - Trullas, Ramon
AU - Shippenberg, Toni S.
N1 - Funding Information:
Funding. This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, SFB Transregio 130, Project 15).
PY - 2012/9/5
Y1 - 2012/9/5
N2 - 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.
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.
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U2 - 10.1523/JNEUROSCI.2730-12.2012
DO - 10.1523/JNEUROSCI.2730-12.2012
M3 - Article
C2 - 22956834
AN - SCOPUS:84865749288
SN - 0270-6474
VL - 32
SP - 12431
EP - 12436
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 36
ER -