title: Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain.
abstract: BACKGROUND
  The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve.
  
  
  METHODS
  Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device.
  
  
  RESULTS
  Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg).
  
  
  CONCLUSIONS
  These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA.
authors.affiliation: Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: A S
authors.initials: AS
authors.lastname: Bura
authors.forename: T
authors.initials: T
authors.lastname: Guegan
authors.forename: D
authors.initials: D
authors.lastname: Zamanillo
authors.forename: J M
authors.initials: JM
authors.lastname: Vela
authors.forename: R
authors.initials: R
authors.lastname: Maldonado
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004644:Emotions; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*; D012646:Self Administration; D000097605:Sigma-1 Receptor
chemical_list: D000700:Analgesics; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor