A Translational Study of the Effects of Ketamine and Pregabalin on Temporal Summation of Experimental Pain. Issue 6 (1st October 2011)

• Record Type: Journal Article
• Authors: Arendt-Nielsen, Lars; Mansikka, Heikki; Staahl, Camilla; Rees, Huw; Tan, Keith; Smart, Trevor S.; Monhemius, Russell; Suzuki, Rie; Drewes, Asbjørn M.
• Is Part Of: Regional anesthesia and pain medicine. Volume 36:Issue 6(2011)
• Page Start: 585-591
• Page End: 585-591
• Publication Date: 2011-10-01
• Subjects: Conduction anesthesia -- Periodicals; Pain medicine -- Periodicals; 617.964
• DOI: 10.1097/AAP.0b013e31822b0db0
• Languages: English
• ISSNs: 1098-7339

Abstract

Abstract : Background and Objectives: 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.