Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain

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 t...

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Published in:	American journal of therapeutics Vol. 23; no. 6; pp. e1484 - e1492
Main Authors:	Stachtari, Chrysoula C, Thomareis, Olympia N, Tsaousi, Georgia G, Karakoulas, Konstantinos A, Chatzimanoli, Foteini I, Chatzopoulos, Stavros A, Vasilakos, Dimitrios G
Format:	Journal Article
Language:	English
Published:	United States 01-11-2016
Subjects:	Analgesics - administration & dosage Analgesics - pharmacology Animals Bornanes - administration & dosage Bornanes - pharmacology Cannabinoids - administration & dosage Cannabinoids - pharmacology Disease Models, Animal Drug Interactions Hot Temperature Inflammation - drug therapy Inflammation - pathology Interleukin-2 - blood Interleukin-6 - blood Male Naloxone - pharmacology Pain Threshold Pain, Postoperative - drug therapy Pain, Postoperative - pathology Pyrazoles - administration & dosage Pyrazoles - pharmacology Random Allocation Rats Rats, Wistar Receptor, Cannabinoid, CB2 - agonists Time Factors Tramadol - administration & dosage Tramadol - pharmacology
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1075-2765 1536-3686
DOI:	10.1097/MJT.0000000000000131