title: A translational study of the effects of ketamine and pregabalin on temporal summation of experimental pain.
abstract: OBJECTIVE
  Central sensitization is often seen in chronic pain. A relevant and potent mechanism of central sensitization is the central integration of nociceptive impulses. Temporal summation in humans and the wind-up process in animals share common features of central integration. This preclinical and clinical translational study investigated the effect of ketamine and pregabalin on temporal summation (TS) and wind-up of wide dynamic range (WDR) neurons of nociceptive electrical stimuli in healthy volunteers and rats.
  
  
  METHODS
  This 3-way crossover study included healthy male volunteers (n = 18) receiving 3 doses of 300 mg pregabalin (orally) over 2 days, ketamine (intravenous loading dose 0.5 mg/kg followed by 9 μg/kg per minute for 20 mins) on the first day, or placebo. The pain detection thresholds to repetitive electrical cutaneous and suprathreshold responses stimulation were assessed.In male Sprague-Dawley rats (n = 30), WDR neuron recordings after electrical stimulation were obtained before and after 15 minutes of intravenous infusion pregabalin (0.127, 0.42, and 1.27 mg/kg per minute) and ketamine (0.006, 0.02, 0.06, and 0.2 mg/kg per minute).
  
  
  RESULTS
  In the human study, ketamine compared with placebo significantly increased the TS pain detection threshold (P < 0.001) and significantly reduced suprathreshold pain responses (P < 0.001). In rats, the highest dose of ketamine significantly inhibited the wind-up response of the WDR neurons (P = 0.014). Pregabalin affected neither of the parameters in TS and WDR responses.
  
  
  CONCLUSIONS
  It was shown that TS shares common features with wind-up of WDR neurons and that pregabalin does not affect this component of central sensitization.
authors.affiliation: Center for Sensory-Motor Interactions, Department of Health Science and Technology, Aalborg University, Denmark. LAN@hst.aau.dk
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: Heikki
authors.initials: H
authors.lastname: Mansikka
authors.forename: Camilla
authors.initials: C
authors.lastname: Staahl
authors.forename: Huw
authors.initials: H
authors.lastname: Rees
authors.forename: Keith
authors.initials: K
authors.lastname: Tan
authors.forename: Trevor S
authors.initials: TS
authors.lastname: Smart
authors.forename: Russell
authors.initials: R
authors.lastname: Monhemius
authors.forename: Rie
authors.initials: R
authors.lastname: Suzuki
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000818:Animals; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D057170:Translational Research, Biomedical / Q000379:methods*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D007649:Ketamine