Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain

J Zhejiang Univ Sci B. 2008 Nov;9(11):895-902. doi: 10.1631/jzus.B0820039.

Abstract

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.

Conclusion: The results suggest that tramadol could be a good choice for the treatment of pain under the conditions that immunosuppression may be particularly contraindicated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / blood
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / blood
  • Male
  • Pain Measurement / methods
  • Pain Threshold / drug effects*
  • Pain, Postoperative / blood
  • Pain, Postoperative / drug therapy*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tramadol / pharmacology*

Substances

  • Analgesics, Opioid
  • Interleukin-2
  • Interleukin-6
  • Tramadol