Alleviation of neuropathic pain hypersensitivity by inhibiting Neuronal pentraxin 1 in the rostral ventromedial medulla

Agustin Zapata, Silvia Pontis, Raf J. Schepers, Ruizhong Wang, Eric Oh, Alexandra Stein, Cristina M. Bäckman, Paul F Worley, Marta Enguita, M. Alba Abad, Ramon Trullas, Toni S. Shippenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)12431-12436
Number of pages6
JournalJournal of Neuroscience
Volume32
Issue number36
DOIs
StatePublished - Sep 5 2012

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Neuralgia
Hyperalgesia
Hypersensitivity
Wounds and Injuries
Pain
Peripheral Nerve Injuries
Neuronal Plasticity
AMPA Receptors
Glutamate Receptors
Knockout Mice
Synapses
Brain Stem
Rodentia
neuronal pentraxin
Brain
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zapata, A., Pontis, S., Schepers, R. J., Wang, R., Oh, E., Stein, A., ... Shippenberg, T. S. (2012). Alleviation of neuropathic pain hypersensitivity by inhibiting Neuronal pentraxin 1 in the rostral ventromedial medulla. Journal of Neuroscience, 32(36), 12431-12436. https://doi.org/10.1523/JNEUROSCI.2730-12.2012

Alleviation of neuropathic pain hypersensitivity by inhibiting Neuronal pentraxin 1 in the rostral ventromedial medulla. / Zapata, Agustin; Pontis, Silvia; Schepers, Raf J.; Wang, Ruizhong; Oh, Eric; Stein, Alexandra; Bäckman, Cristina M.; Worley, Paul F; Enguita, Marta; Alba Abad, M.; Trullas, Ramon; Shippenberg, Toni S.

In: Journal of Neuroscience, Vol. 32, No. 36, 05.09.2012, p. 12431-12436.

Research output: Contribution to journalArticle

Zapata, A, Pontis, S, Schepers, RJ, Wang, R, Oh, E, Stein, A, Bäckman, CM, Worley, PF, Enguita, M, Alba Abad, M, Trullas, R & Shippenberg, TS 2012, 'Alleviation of neuropathic pain hypersensitivity by inhibiting Neuronal pentraxin 1 in the rostral ventromedial medulla', Journal of Neuroscience, vol. 32, no. 36, pp. 12431-12436. https://doi.org/10.1523/JNEUROSCI.2730-12.2012
Zapata, Agustin ; Pontis, Silvia ; Schepers, Raf J. ; Wang, Ruizhong ; Oh, Eric ; Stein, Alexandra ; Bäckman, Cristina M. ; Worley, Paul F ; Enguita, Marta ; Alba Abad, M. ; Trullas, Ramon ; Shippenberg, Toni S. / Alleviation of neuropathic pain hypersensitivity by inhibiting Neuronal pentraxin 1 in the rostral ventromedial medulla. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 36. pp. 12431-12436.
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