title: ARA290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain: an experimental study in rats and β-common receptor knockout mice.
abstract: BACKGROUND
  Exogenous erythropoietin inhibits development of allodynia in experimental painful neuropathy because of its antiinflammatory and neuroprotective properties at spinal, supraspinal, and possibly peripheral sites. The authors assess the effect of a nonhematopoietic erythropoietin analog, ARA290, on tactile and cold allodynia in a model of neuropathic pain (spared nerve injury) in rats and mice lacking the β-common receptor (βcR mice), a component of the receptor complex mediating tissue protection.
  
  
  METHODS
  Twenty-four hours after peripheral nerve injury, rats and mice were injected with ARA290 or vehicle (five 30-μg/kg intraperitoneal injections at 2-day intervals, followed by once/week, n = 8/group). In a separate group of eight rats, ARA290 treatment was restricted to five doses during the initial 2 weeks after surgery.
  
  
  RESULTS
  In rats, irrespective of treatment paradigm, ARA290 produced effective, long-term (as long as 15 weeks) relief of tactile and cold allodynia (P < 0.001 vs. vehicle-treated animals). ARA290 was effective in wild-type mice, producing significant relief of allodynia. In contrast, in βcR mice no effect of ARA290 was observed.
  
  
  CONCLUSIONS
  ARA290 produces long-term relief of allodynia because of activation of the β-common receptor. It is argued that relief of neuropathic pain attributable to ARA290 treatment is related to its antiinflammatory properties, possibly within the central nervous system. Because ARA290, in contrast to erythropoietin, is devoid of hematopoietic and cardiovascular side effects, ARA290 is a promising new drug in the prevention of peripheral nerve injury-induced neuropathic pain in humans.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Swartjes
authors.forename: Aurora
authors.initials: A
authors.lastname: Morariu
authors.forename: Marieke
authors.initials: M
authors.lastname: Niesters
authors.forename: Michael
authors.initials: M
authors.lastname: Brines
authors.forename: Anthony
authors.initials: A
authors.lastname: Cerami
authors.forename: Leon
authors.initials: L
authors.lastname: Aarts
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
mesh_terms: D000818:Animals; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000737:chemistry; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy; D051379:Mice; D018345:Mice, Knockout; D009437:Neuralgia / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
chemical_list: D010455:Peptides; D017467:Receptors, Erythropoietin; D004921:Erythropoietin