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Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.11 P.895-902

http://doi.org/10.1631/jzus.B0820039


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


Author(s):  Yong-min LIU, Sheng-mei ZHU, Kui-rong WANG, Zhi-ying FENG, Qing-lian CHEN

Affiliation(s):  Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

Corresponding email(s):   smzhu20088@yahoo.com.cn

Key Words:  Tramadol, Pain, Mechanical allodynia, Interleukin-6 (IL-6), Interleukin-2 (IL-2), Rat


Yong-min LIU, Sheng-mei ZHU, Kui-rong WANG, Zhi-ying FENG, Qing-lian CHEN. Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain[J]. Journal of Zhejiang University Science B, 2008, 9(11): 895-902.

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author="Yong-min LIU, Sheng-mei ZHU, Kui-rong WANG, Zhi-ying FENG, Qing-lian CHEN",
journal="Journal of Zhejiang University Science B",
volume="9",
number="11",
pages="895-902",
year="2008",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0820039"
}

%0 Journal Article
%T Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain
%A Yong-min LIU
%A Sheng-mei ZHU
%A Kui-rong WANG
%A Zhi-ying FENG
%A Qing-lian CHEN
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 11
%P 895-902
%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820039

TY - JOUR
T1 - Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain
A1 - Yong-min LIU
A1 - Sheng-mei ZHU
A1 - Kui-rong WANG
A1 - Zhi-ying FENG
A1 - Qing-lian CHEN
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 11
SP - 895
EP - 902
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
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 2~5 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 μg/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 μg/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.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1] Apaydin, S., Uyar, M., Karabay, N.U., Erhan, E., Yegul, I., Tuglular, I., 2000. The antinociceptive effect of tramadol on a model of neuropathic pain in rats. Life Sci., 66(17):1627-1637.

[2] Berrocoso, E., de Benito, M.D., Mico, J.A., 2007. Role of serotonin 5-HT1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats. Psychopharmacology (Berl.), 193(1):97-105.

[3] Brennan, T.J., Vandermeulen, E.P., Gebhart, G.F., 1996. Characterization of a rat model of incisional pain. Pain, 64(3):493-501.

[4] Clancy, J., Lorens, S.Jr., 1996. Subchronic and chronic exposure to D-fenfluramine dose-dependently enhances splenic immune functions in young and old male Fischer-344 rats. Behav. Brain Res., 73(1-2):355-358.

[5] Clark, J.D., Shi, X., Li, X., Qiao, Y., Liang, D., Angst, M.S., Yeomans, D.C., 2007. Morphine reduces local cytokine expression and neutrophil infiltration after incision. Mol. Pain, 3(1):28.

[6] Damas, P., Ledoux, D., Nys, M., Vrindts, Y., Groote, D.D., Franchimont, P., Lamy, M., 1992. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann. Surg., 215(4):356-362.

[7] de Sarro, G.B., Nisticò, G., 1990. Naloxone antagonizes behavioural and ECoG effects induced by systemic or intracerebral administration of some lymphokines. Ann. Ist. Super. Sanita, 26(1):99-106.

[8] El-Nour, H., Lundeberg, L., Abdel-Magid, N., Lonne-Rahm, S.B., Azmitia, E.C., Nordlind, K., 2007. Serotonergic mechanisms in human allergic contact dermatitis. Acta Derm. Venereol., 87(5):390-396.

[9] Gaspani, L., Bianchi, M., Limiroli, E., Panerai, A.E., Sacerdote, P., 2002. The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats. J. Neuroimmunol., 129(1-2):18-24.

[10] Hashioka, S., Klegeris, A., Monji, A., Kato, T., Sawada, M., McGeer, P.L., Kanba, S., 2007. Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp. Neurol., 206(1):33-42.

[11] Hensler, T., Hecker, H., Heeq, K., Heidecke, C.D., Bartels, H., Barthlen, W., Wagner, H., Siewert, J.R., Holzmann, B., 1997. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect. Immun., 65(6):2283-2291.

[12] Kayser, V., Besson, J.M., Guilbaud, G., 1992. Evidence for a noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic rat. Eur. J. Pharmacol., 224(1):83-88.

[13] Lin, E., Calvano, S.E., Lowry, S.F., 2000. Inflammatory cytokines and cell response in surgery. Surgery, 127(2):117-126.

[14] Lynch, M.E., 2001. Antidepressants as analgesics: a review of randomized controlled trials. J. Psychiatry Neurosci., 26(1):30-36.

[15] Maes, M., 2001. The immunoregulatory effects of antidepressants. Hum. Psychopharmacol. Clin. Exp., 16(1):95-103.

[16] Manfredi, B., Sacerdote, P., Bianchi, M., Locatelli, L., Veljic-Radulovic, J., Panerai, A.E., 1993. Evidence for an opioid inhibitory effect on T cell proliferation. J. Neuroimmunol., 44(1):43-48.

[17] McBride, W.T., Armstrong, M.A., McBride, S.J., 1996. Immunomodulation: an important concept in modern anaesthesia. Anaesthesia, 51(5):465-473.

[18] Nagahiro, I., Andou, A., Aoe, M., Sano, Y., Date, H., Shimizu, N., 2001. Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure. Ann. Thorac. Surg., 72(2):362-365.

[19] Niemand, C., Nimmesgern, A., Haan, S., Fischer, P., Schaper, F., Rossaint, R., Heinrich, P.C., Müller-Newen, G., 2003. Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3. J. Immunol., 170(6):3263-3272.

[20] Oliva, P., Aurilio, C., Massimo, F., Grella, A., Maione, S., Grella, E., Scafuro, M., Rossi, F., Berrino, L., 2002. The antinociceptive effect of tramadol in the formalin test is mediated by the serotonergic component. Eur. J. Pharmacol., 445(3):179-185.

[21] Panerai, A.E., Manfredi, B., Granucci, F., Sacerdote, P., 1995. The beta-endorphin inhibition of mitogen-induced splenocytes proliferation is mediated by central and peripheral paracrine/autocrine effects of the opioid. J. Neuroimmunol., 58(1):71-76.

[22] Peterson, P.K., Molitor, T.W., Chao, C.C., 1993. Mechanisms of morphine-induced immunomodulation. Biochem. Pharmacol., 46(3):343-348.

[23] Plata-Salamán, C.R., Ffrench-Mullen, J.M., 1993. Interleukin-2 modulates calcium currents in dissociated hippocampal CA1 neurons. Neuroreport, 4(5):579-581.

[24] Raeburn, C.D., Sheppard, F., Barsness, K.A., Arya, J., Harken, A.H., 2002. Cytokines for surgeons. Am. J. Surg., 183(3):268-273.

[25] Raffa, R.B., 1996. A novel approach to the pharmacology of analgesics. Am. J. Med., 101(1A):S40-S46.

[26] Raffa, R.B., Friderichs, E., Reimann, W., Shank, R.P., Codd, E.E., Vaught, J.L., 1992. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J. Pharmacol. Exp. Ther., 260(1):275-285.

[27] Reimann, W., Hennies, H.H., 1994. Inhibition of spinal noradrenaline uptake in rats by the centrally acting analgesic tramadol. Biochem. Pharmacol., 47(12):2289-2293.

[28] Sacerdote, P., Bianchi, M., Manfredi, B., Panerai, A.E., 1997. Effects of tramadol on immune responses and nociceptive thresholds in mice. Pain, 72(3):325-330.

[29] Sacerdote, P., Bianchi, M., Gaspani, L., Panerai, A.E., 1999. Effects of tramadol and its enantiomers on concanavalin-A-induced proliferation and NK activity of mouse splenocytes: involvement of serotonin. Int. J. Immunopharmacol., 21(11):727-734.

[30] Sacerdote, P., Bianchi, M., Gaspani, L., Manfredi, B., Maucione, A., Terno, G., Ammatuna, M., Panerai, A.E., 2000. The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Anesth. Analg., 90(6):1411-1414.

[31] Salo, M., 1992. Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol. Scand., 36(3):201-220.

[32] Sheeran, P., Hall, G.M., 1997. Cytokines in anaesthesia. Br. J. Anaesth., 78(2):201-219.

[33] Song, P., Zhao, Z.Q., 2000. Interleukin 2-induced antinociception partially coupled with μ-receptor. Cytokine, 12(8):1240-1242.

[34] Song, P., Lie-Cheng, W., Wang, G.D., Zhou, Z., Zhao, Z.Q., 2002a. Interleukin-2 regulates membrane potentials and calcium channels via mu opioid receptors in rat dorsal root ganglion neurons. Neuropharmacology, 43(8):1324-1329.

[35] Song, P., Liu, X.Y., Zhao, Z.Q., 2002b. Interleukin-2-induced antinociception in morphine-insensitive rats. Acta Pharmacol. Sin., 23(11):981-984.

[36] St A Stewart, L., Martin, W.J., 2003. Evaluation of postoperative analgesia in a rat model of incisional pain. Contemp. Top. Lab. Anim. Sci., 42(1):28-34.

[37] Wang, W., Danielsson, A., Svanberg, E., Lundholm, K., 2003. Lack of effects by tricyclic antidepressant and serotonin inhibitors on anorexia in MCG 101 tumor-bearing mice with eicosanoid-related cachexia. Nutrition, 19(1):47-53.

[38] Whiteside, G.T., Harrison, J., Boulet, J., Mark, L., Pearson, M., Gottshall, S., Walker, K., 2004. Pharmacological characterisation of a rat model of incisional pain. Br. J. Pharmacol., 141(1):85-91.

[39] Yim, A.P., Wan, S., Lee, T.W., Arifi, A.A., 2000. VAST lobectomy reduces cytokine responses compared with conventional surgery. Ann. Thorac. Surg., 70(1):243-247.

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