title: Controlling the activation of the Bv8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals.
abstract: OBJECTIVE
  Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2 ) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain.
  
  
  METHODS
  Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (CCI). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI, following treatment for 1 week with saline or PC1. IL-1β and IL-10 levels, along with glia activation, were evaluated.
  
  
  RESULTS
  Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI-induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR2 were up-regulated in nociceptors, in Schwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury-induced overexpression of PROK2, significantly blunted nerve injury-induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti-inflammatory cytokines in periphery and in spinal cord.
  
  
  CONCLUSIONS
  The prokineticin system contributes to pain modulation via neuron-glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.
authors.affiliation: Department of Physiology and Pharmacology 'Vittorio Erspamer', University of Rome, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Maftei
authors.forename: V
authors.initials: V
authors.lastname: Marconi
authors.forename: F
authors.initials: F
authors.lastname: Florenzano
authors.forename: L A
authors.initials: LA
authors.lastname: Giancotti
authors.forename: M
authors.initials: M
authors.lastname: Castelli
authors.forename: S
authors.initials: S
authors.lastname: Moretti
authors.forename: E
authors.initials: E
authors.lastname: Borsani
authors.forename: L F
authors.initials: LF
authors.lastname: Rodella
authors.forename: G
authors.initials: G
authors.lastname: Balboni
authors.forename: L
authors.initials: L
authors.lastname: Luongo
authors.forename: S
authors.initials: S
authors.lastname: Maione
authors.forename: P
authors.initials: P
authors.lastname: Sacerdote
authors.forename: L
authors.initials: L
authors.lastname: Negri
authors.forename: R
authors.initials: R
authors.lastname: Lattanzi
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D005768:Gastrointestinal Hormones; C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D009479:Neuropeptides; C525015:PKR1 protein, mouse; C525016:PKR2 protein, mouse; C486586:Prok2 protein, mouse; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D016753:Interleukin-10