Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain.
OBJECTIVE
To evaluate the effects of tramadol on the proinflammatory responses in a rat model of incisional pain by investigating its effects on nociceptive thresholds and serum interleukin-6 (IL-6) and IL-2 levels.


METHODS
Forty-two male Sprague-Dawley (SD) rats scheduled for plantar incision were randomly divided into 7 groups (n=6 in each group). Rats in Group 1 receiving general anesthesia with no incision were served as control; At 30 min before skin incision, Groups 2 to approximately 5 were given 5 ml normal saline or 1, 10, and 20 mg/kg tramadol, respectively, intraperitoneally (i.p.); Group 6 received 10 mg/kg tramadol after operation; Group 7 received 10 mg/kg tramadol before incision, followed by 200 microg/kg naloxone after operation. Mechanical allodynia was measured by electronic von Frey filament to evaluate the nociceptive thresholds 1 h before incision, and 1 h and 2 h after operation. Serum IL-6 and IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA) 2 h after operation.


RESULTS
Mechanical thresholds decreased significantly and serum IL-6 level increased significantly after operation in Group 2 compared with control (P<0.01), and these changes were reversed respectively by tramadol in a dose-dependent manner (P<0.05 and P<0.01, respectively). IL-2 level remained unchanged after operation in Group 2, but decreased in Group 3 (P<0.05), then gradually returned to the normal level in Groups 4 and 5. The intraperitoneally injected tramadol (10 and 20 mg/kg) produced a potent and dose-dependent antinocicptive effect on the lesioned paw. The antinocicptive effects of tramadol were partially antagonized by naloxone (200 microg/kg), suggesting an additional non-opioid mechanism.


CONCLUSIONS
The results suggest that tramadol could be a good choice for the treatment of pain under the conditions that immunosuppression may be particularly contraindicated.
Liu
Yong-Min
YM
Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Zhu
Sheng-Mei
SM
Wang
Kui-Rong
KR
Feng
Zhi-Ying
ZY
Chen
Qing-Lian
QL
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D010149:Postoperative Pain / Q000097:blood / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000494:pharmacology*
D000701:Analgesics, Opioid; D007376:Interleukin-2; D015850:Interleukin-6; D014147:Tramadol