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Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain.
Am J Ther 2016 Nov/Dec; 23(6):e1484-e1492AJ

Abstract

The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain. Prospective randomized trial assessing the individual or combined application of intraperitoneal tramadol (10 mg/kg) and the selective cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress stimulus. Pharmacological specificity was established by antagonizing tramadol with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120) minutes after incision. Blood samples for plasma IL-6 and IL-2 level determination were obtained 2 hours after incision. Data from 42 rats were included in the final analyses. Significant augmentation of thermal threshold was observed at all time points, after administration of either tramadol or (R,S)-AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively). The combination of (R,S)-AM1241 plus tramadol promoted the induced antinociception in an important manner compared with control (P = 0.002) and (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P = 0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241 administration in a significant manner (P = 0.001) at all time points. Similarly, naloxone plus SR144528 also blocked the effects of the combination of (R,S)-AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241 plus tramadol group was significantly attenuated compared with control group (P = 0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups. It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may improve antinociceptive effects and immune responses of cannabinoids, but this effect does not seem to be superior to that of tramadol alone.

Authors+Show Affiliations

1Department of Anesthesiology, Faculty of Medicine, Aristotle University, Thessaloniki, Greece; 2Department of Microbiology and Immunology, Theagenio Cancer Hospital, Thessaloniki, Greece; and 3Department of Mathematics, Aristotle University, Thessaloniki, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

25370921

Citation

Stachtari, Chrysoula C., et al. "Interaction of a Cannabinoid-2 Agonist With Tramadol On Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain." American Journal of Therapeutics, vol. 23, no. 6, 2016, pp. e1484-e1492.
Stachtari CC, Thomareis ON, Tsaousi GG, et al. Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain. Am J Ther. 2016;23(6):e1484-e1492.
Stachtari, C. C., Thomareis, O. N., Tsaousi, G. G., Karakoulas, K. A., Chatzimanoli, F. I., Chatzopoulos, S. A., & Vasilakos, D. G. (2016). Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain. American Journal of Therapeutics, 23(6), pp. e1484-e1492.
Stachtari CC, et al. Interaction of a Cannabinoid-2 Agonist With Tramadol On Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain. Am J Ther. 2016;23(6):e1484-e1492. PubMed PMID: 25370921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain. AU - Stachtari,Chrysoula C, AU - Thomareis,Olympia N, AU - Tsaousi,Georgia G, AU - Karakoulas,Konstantinos A, AU - Chatzimanoli,Foteini I, AU - Chatzopoulos,Stavros A, AU - Vasilakos,Dimitrios G, PY - 2014/11/6/pubmed PY - 2017/2/28/medline PY - 2014/11/6/entrez SP - e1484 EP - e1492 JF - American journal of therapeutics JO - Am J Ther VL - 23 IS - 6 N2 - The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain. Prospective randomized trial assessing the individual or combined application of intraperitoneal tramadol (10 mg/kg) and the selective cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress stimulus. Pharmacological specificity was established by antagonizing tramadol with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120) minutes after incision. Blood samples for plasma IL-6 and IL-2 level determination were obtained 2 hours after incision. Data from 42 rats were included in the final analyses. Significant augmentation of thermal threshold was observed at all time points, after administration of either tramadol or (R,S)-AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively). The combination of (R,S)-AM1241 plus tramadol promoted the induced antinociception in an important manner compared with control (P = 0.002) and (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P = 0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241 administration in a significant manner (P = 0.001) at all time points. Similarly, naloxone plus SR144528 also blocked the effects of the combination of (R,S)-AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241 plus tramadol group was significantly attenuated compared with control group (P = 0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups. It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may improve antinociceptive effects and immune responses of cannabinoids, but this effect does not seem to be superior to that of tramadol alone. SN - 1536-3686 UR - https://www.unboundmedicine.com/medline/citation/25370921/Interaction_of_a_Cannabinoid_2_Agonist_With_Tramadol_on_Nociceptive_Thresholds_and_Immune_Responses_in_a_Rat_Model_of_Incisional_Pain_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1075-2765&volume=23&issue=6&spage=e1484&aulast=Stachtari DB - PRIME DP - Unbound Medicine ER -