title: Alleviation of neuropathic pain hypersensitivity by inhibiting neuronal pentraxin 1 in the rostral ventromedial medulla.
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.
authors.affiliation: Integrative Neuroscience Branch, National Institute on Drug Abuse, NIH, Baltimore, Maryland 21224, USA. Azapata@mail.nih.gov
authors.forename: Agustin
authors.initials: A
authors.lastname: Zapata
authors.forename: Silvia
authors.initials: S
authors.lastname: Pontis
authors.forename: Raf J
authors.initials: RJ
authors.lastname: Schepers
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Wang
authors.forename: Eric
authors.initials: E
authors.lastname: Oh
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stein
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Bäckman
authors.forename: Paul
authors.initials: P
authors.lastname: Worley
authors.forename: Marta
authors.initials: M
authors.lastname: Enguita
authors.forename: M Alba
authors.initials: MA
authors.lastname: Abad
authors.forename: Ramon
authors.initials: R
authors.lastname: Trullas
authors.forename: Toni S
authors.initials: TS
authors.lastname: Shippenberg
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D009474:Neurons / Q000378:metabolism; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D000099153:Pentraxins