Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model.
OBJECTIVE
Ketamine is an N-Methyl-D-Aspartate (NMDA) receptor antagonist, which has been found to effectively treat somatic and neuropathic pain. This study examines the effect (on neuropathic pain) of preemptive ketamine using different routes of administration (intrathecal versus intraperitoneal).


METHODS
The Institutional Animal Care and Use Committee approved the study. Thirty male Sprague-Dawley rats (250-275 g) were divided into three treatment groups [intrathecal saline/intraperitoneal saline or Control (CTL), intrathecal ketamine/intraperitoneal saline (ITK), and intrathecal saline/intraperitoneal ketamine (IPK)] prior to undergoing surgery to induce neuropathic pain by tight ligation of the left L5 and L6 spinal nerves. All drugs were given 15 minutes before nerve ligation. The ITK group received intrathecal ketamine (0.5% solution, 1 mg/kg), the IPK group received intraperitoneal ketamine (0.5% solution, 1 mg/kg), saline was given in equal volume (approximately 0.05 mL). Mechanical allodynia, cold allodynia, and ongoing pain behaviors indicative of neuropathic pain were assessed on postoperative days 1, 3, 7, and 14 using validated methods.


RESULTS
Compared with the CTL group, the ITK group showed a state of decreased mechanical allodynia, cold allodynia, and ongoing pain as revealed by the von Frey hair, acetone, and cold plate testing, respectively. Further, this decrease was sustained for at least 2 weeks. The IPK group showed intermediate results between the CTL and ITK.


CONCLUSIONS
Neuropathic pain behaviors were significantly reduced for at least 2 weeks after intrathecal ketamine was preemptively administered to animals undergoing surgery to induce neuropathic pain. The mechanism of action is thought to be prevention of spinal cord sensitization.
Burton
A W
AW
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0591, USA.
Lee
D H
DH
Saab
C
C
Chung
J M
JM
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D007649:Ketamine / Q000627:therapeutic use*; D008026:Ligation; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D013127:Spinal Nerves / Q000601:surgery
D000700:Analgesics; D012965:Sodium Chloride; D007649:Ketamine