title: Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats.
abstract: OBJECTIVE
  Neuropathic pain is difficult to manage and treat. Spinal cord stimulation (SCS) has become an established procedure for treating chronic neuropathic pain that is refractory to pharmacological therapy. In order to achieve better analgesia, a number of studies have evaluated the effectiveness of combining drug therapy with SCS. Cholecystokinin antagonists, such as proglumide, enhance the analgesic efficacy of endogenous opioids in animal models of pain. We previously reported that both systemic and spinal administration of proglumide enhances analgesia produced by both low- and high-frequency transcutaneous electrical nerve stimulation (TENS). Since SCS produces analgesia through endogenous opioids, we hypothesized that the analgesic effect of SCS would be enhanced through co-administration with proglumide in animals with neuropathic pain.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 40) with spared nerve injury were given proglumide (20 mg/kg, i.p.) or saline prior to treatment with SCS (sham, 4 Hz, and 60 Hz). Mechanical withdrawal thresholds of the paw were measured before and after induction of nerve injury, and after SCS. Physical activity levels were measured after SCS.
  
  
  RESULTS
  Both proglumide and SCS when given independently significantly increased withdrawal thresholds two weeks after nerve injury. However, there was no additional effect of combining proglumide and SCS on mechanical withdrawal thresholds or activity levels in animals with nerve injury.
  
  
  CONCLUSIONS
  Proglumide may be a candidate for achieving analgesia for patients with refractory neuropathic pain conditions, but does not enhance analgesia produced by SCS.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, the University of Iowa, Iowa City, Iowa, USA.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Medtronic Neuromodulation, Medtronic, Inc, Minneapolis, Minnesota, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Johanek
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, the University of Iowa, Iowa City, Iowa, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
mesh_terms: D000698:Analgesia / Q000379:methods*; D000818:Animals; D003131:Combined Modality Therapy / Q000379:methods; D008297:Male; D009437:Neuralgia / Q000473:pathology / Q000628:therapy*; D010147:Pain Measurement / Q000379:methods*; D011377:Proglumide / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D062187:Spinal Cord Stimulation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D011949:Receptors, Cholecystokinin; D011377:Proglumide
keywords: Combination therapy; neuropathic pain; neurostimulation; proglumide; spinal cord stimulation