PMID- 23936499
OWN - NLM
STAT- MEDLINE
DCOM- 20140318
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Ketamine does not produce relief of neuropathic pain in mice lacking the beta-common 
      receptor (CD131).
PG  - e71326
LID - 10.1371/journal.pone.0071326 [doi]
LID - e71326
AB  - Neuropathic pain (NP) is a debilitating condition associated with traumatic, 
      metabolic, autoimmune and neurological etiologies. Although the triggers for NP 
      are diverse, there are common underlying pathways, including activation of immune 
      cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor 
      (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a 
      sustained manner. Recent study has shown that the novel 11-amino acid peptide 
      erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP. 
      Here, we show that both drugs also have similar effects on the expression of mRNA 
      of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) 
      ligand 2, all-important contributors to the development of NP. Although the 
      effects of ketamine and ARA 290 on NP and its molecular mediators suggest a 
      common mechanism of action, ARA 290 has no affinity for the NMDAR and acts 
      specifically via the innate repair receptor (IRR) involved in tissue protection. 
      We speculated therefore, that the IRR might be critically involved in the action 
      of ketamine on neuropathic pain. To evaluate this, we studied the effects of 
      ketamine and ARA 290 on acute pain, side effects, and allodynia following a 
      spared nerve injury model in mice lacking the beta-common receptor (betacR), a 
      structural component of the IRR. Ketamine (50 mg/kg) and ARA 290 (30 microg/kg) 
      produced divergent effects on acute pain: ketamine produced profound 
      antinociception accompanied with psychomotor side effects, but ARA290 did not, in 
      both normal and knock out mice. In contrast, while both drugs were antiallodynic 
      in WT mice, they had no effect on NP in mice lacking the betacR. Together, these 
      results show that an intact IRR is required for the effective treatment of NP 
      with either ketamine or ARA 290, but is not involved in ketamine's analgesic and 
      side effects.
FAU - Swartjes, Maarten
AU  - Swartjes M
AD  - Department of Anesthesiology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Niesters, Marieke
AU  - Niesters M
FAU - Heij, Lara
AU  - Heij L
FAU - Dunne, Ann
AU  - Dunne A
FAU - Aarts, Leon
AU  - Aarts L
FAU - Hand, Carla Cerami
AU  - Hand CC
FAU - Kim, Hyung-Suk
AU  - Kim HS
FAU - Brines, Michael
AU  - Brines M
FAU - Cerami, Anthony
AU  - Cerami A
FAU - Dahan, Albert
AU  - Dahan A
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130801
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokine Receptor Common beta Subunit)
RN  - 0 (Oligopeptides)
RN  - 0 (RNA, Messenger)
RN  - 690G0D6V8H (Ketamine)
RN  - 9W5677JKDA (cibinetide)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Cytokine Receptor Common beta Subunit/*deficiency/*genetics
MH  - Female
MH  - *Gene Knockout Techniques
MH  - Ketamine/*pharmacology/therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuralgia/*drug therapy/genetics/metabolism
MH  - Nociception/drug effects
MH  - Oligopeptides/pharmacology/therapeutic use
MH  - RNA, Messenger/genetics/metabolism
MH  - Spinal Cord/drug effects/metabolism
PMC - PMC3731332
COIS- Competing Interests: Ann Dunne, Michael Brines and Anthony Cerami are employees 
      of Araim Pharmaceuticals Inc. (Ossining, New York), which is developing 
      nonerythropoietic tissue protective compounds for clinical use. This does not 
      alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials. The other authors declare no conflict of interest or competing 
      interests.
EDAT- 2013/08/13 06:00
MHDA- 2014/03/19 06:00
PMCR- 2013/08/01
CRDT- 2013/08/13 06:00
PHST- 2013/04/10 00:00 [received]
PHST- 2013/06/27 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - PONE-D-13-15383 [pii]
AID - 10.1371/journal.pone.0071326 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 1;8(8):e71326. doi: 10.1371/journal.pone.0071326. Print 2013.