Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal cord injury.
Spinal cord injury (SCI) pain in humans is difficult to treat, and the lack of valid methods to measure behavior comparable to the complex human pain experience preclinically represents an important obstacle to finding better treatments for this type of central pain. The place escape/avoidance paradigm (PEAP) relies on the active choice of an animal between its natural preference for a dark environment or pain relief, and it has been suggested to measure the affective-motivational component of pain. We have modified the method to a T10 spinal cord contusion model (SCC) of at-level central neuropathic pain in Sprague-Dawley rats. In order to demonstrate sensitivity to change in escape/avoidance behavior and thus the applicability of the PEAP method to predict drug efficacy, we investigated the effect of pregabalin (30 mg/kg) treatment in a randomized design. SCC animals displayed increased escape/avoidance behavior postinjury, indicating at-level mechanical hypersensitivity. Second, we found no correlation between state anxiety levels in SCC animals (elevated plus maze) and PEAP behavior, suggesting that the PEAP measurement is not biased by differences in anxiety levels. Third, we demonstrated a decrease in escape/avoidance behavior in response to treatment with the analgesic drug pregabalin. Thus, the PEAP may be applicable as a surrogate correlate of human pain. In conclusion, the primary finding in this study was a sensitivity to change in escape/avoidance behavior induced by pharmacological modulation with analgesics, supporting the use of the PEAP as a central outcome measure in preclinical SCI pain research.
Danish Pain Research Center, Aarhus University Hospital, Noerrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark. cathrine.baastrup@ki.au.dk
Cathrine
C
Baastrup
Troels Staehelin
TS
Jensen
Nanna Brix
NB
Finnerup
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects / Q000502:physiology; D005260:Female; D009483:Neuropsychological Tests / Q000592:standards; D017063:Outcome Assessment, Health Care / Q000379:methods; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid