title: The interaction between antidepressant drugs and the pain-relieving effect of spinal cord stimulation in a rat model of neuropathy.
abstract: BACKGROUND
  Spinal cord stimulation (SCS) has proven to be a valuable treatment in neuropathic pain. On the basis of our previous studies on the mode of action of SCS, intrathecal administration of subeffective doses of certain drugs has been shown to enhance the pain-relieving effect in patients with SCS. Antidepressants have a well-established beneficial effect in neuropathic pain. We performed the present study to examine potential synergistic or antagonistic effects on SCS of antidepressants: amitriptyline (tricyclic antidepressant), fluoxetine (selective serotonin reuptake inhibitor), and milnacipran (selective serotonin/noradrenaline reuptake inhibitor).
  
  
  METHODS
  In rats, the effect of SCS on mechanical hypersensitivity after peripheral nerve injury was assessed in awake, freely moving animals. Antidepressants were administered intrathecally.
  
  
  RESULTS
  When combining SCS with subeffective doses of amitriptyline or milnacipran, the suppressive effect of SCS on the mechanical hypersensitivity was enhanced in comparison with that obtained with SCS alone. There was no detectable effect of fluoxetine. No signs of an antagonistic effect of the drugs on the SCS effect were observed.
  
  
  CONCLUSIONS
  These findings suggest a possible clinical application with a combination of SCS and a tricyclic antidepressant or selective serotonin/noradrenaline reuptake inhibitor drug in cases in which SCS per se has proven inefficient.
authors.affiliation: Department of Clinical Neuroscience, Section of Clinical CNS Research, R2:02, Karolinska University Hospital, S-171 76 Stockholm, Sweden. zhiyang.song@ki.se
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Song
authors.forename: Björn A
authors.initials: BA
authors.lastname: Meyerson
authors.forename: Bengt
authors.initials: B
authors.lastname: Linderoth
mesh_terms: D000639:Amitriptyline / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003521:Cyclopropanes / Q000627:therapeutic use; D004567:Electrodes, Implanted; D005473:Fluoxetine / Q000627:therapeutic use; D008026:Ligation; D008297:Male; D000078764:Milnacipran; D010146:Pain / Q000188:drug therapy*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000628:therapy*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000628:therapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013116:Spinal Cord / Q000502:physiology*; D004561:Transcutaneous Electric Nerve Stimulation
chemical_list: D000639:Amitriptyline; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D003521:Cyclopropanes; D005473:Fluoxetine; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors