Ketamine, an N-methyl-D-aspartate receptor antagonist, inhibits the reflex responses to distension of the rat urinary bladder.
BACKGROUND
Ketamine is analgesic in experimental and clinical studies of inflammatory, neuropathic, and postoperative pain. Its role in the treatment of visceral pain is less known. The authors investigated the effect and site of action of ketamine on reflex responses evoked by urinary bladder distension (UBD). The effects of other clinically available N-methyl-d-aspartate (NMDA) receptor antagonists on these responses were also studied.


METHODS
The effect of intravenous ketamine (1, 3, and 10 mg/kg), dextromethorphan (5 mg/kg), and memantine (16 mg/kg) on mean arterial pressure changes (Delta MAP) and abdominal electromyographic activity (EMG) evoked by UBD was measured in anesthetized rats. Ketamine was also administered intravesically and intrathecally and its effect on Delta MAP and EMG responses to UBD recorded. The effect of pretreatment with intravenous ketamine on these responses was also assessed.


RESULTS
The Delta MAP and EMG responses to UBD were reduced in a dose-dependent fashion by ketamine. Memantine and dextromethorphan also inhibited these responses. Ketamine administered intrathecally produced marked inhibition of Delta MAP and EMG responses to UBD. Pretreatment with ketamine only transiently reduced the vigor of responses to UBD.


CONCLUSIONS
Ketamine inhibited, in a dose-dependent fashion, the Delta MAP and EMG responses to UBD, an effect likely caused by actions within the spinal cord. Similar inhibition observed with systemic dextromethorphan and memantine treatments suggests that the analgesic effect of ketamine is caused by antagonism of the NMDA receptor. Pretreatment with ketamine did not have a preventive effect in this model of bladder nociception.
Castroman
Pablo J
PJ
Departmento de Fisiopatología, Faculdade de Medicina, Universidad de la República, Montevideo, Uruguay.
Ness
Timothy J
TJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003915:Dextromethorphan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D008559:Memantine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D003915:Dextromethorphan; D008559:Memantine