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Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat.
Eur J Pharmacol. 2000 May 19; 396(2-3):85-92.EJ

Abstract

It has been suggested that administration of a cannabinoid CB(1) (SR141716A ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide) and CB(2) (SR144528 ¿N-[(1S)-endo-1, 3, 3-trimethyl bicyclo ¿2.2.1 heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyr azo le- 3-carboxamide¿) receptor antagonists to mice potentiates inflammatory hyperalgesia by removing an endogenous cannabinoid tone. We examined whether the behavioural response to s.c. formalin injection in rats is similarly enhanced. A total of 30 animals received SR141716A (0.5 or 5 mg/kg) or SR144528 (0.3 or 3 mg/kg) 30 min before 1% formalin. Pain behaviour was quantified using the composite weighted pain score technique (CPS-WST(0,1,2)). An overall CPS-WST(0,1,2) was calculated for each phase and groups were compared (analysis of variance). The results obtained in the control group confirmed the characteristic biphasic behavioural response to formalin injection. None of antagonist groups had a significant increase in overall CPS-WST(0,1,2) compared to the control. Indeed, a significant decrease in CPS-WST(0,1,2) scores for both phases was detected in most of all of the groups, except SR141716A at 5 mg/kg. Levels of endogenous cannabinoids (anandamide, palmitoylethanolamide, 2-arachidonylglycerol) were measured from rats hind-paw skin 1 h after s.c. injection of 0.9% saline (100 microl), 1% (50 microl), 2. 5% (50 microl) and 5% (100 microl) formalin. The concentration of endocannabinoids did not differ between control and formalin-induced inflammation groups. The activity of anandamide amidohydrolase in hind-paw skin also did not change after treatment with formalin. In conclusion, cannabinoid antagonists do not enhance formalin-evoked pain behaviour. These results suggest that, in this model, endogenous cannabinoids do not tonically attenuate inflammatory hyperalgesia.

Authors+Show Affiliations

Pain Research Group, Department of Anaesthetics, Imperial College School of Medicine, St. Mary's Hospital Campus, Praed Street, W2 1NY, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10822060

Citation

Beaulieu1, P, et al. "Role of the Endogenous Cannabinoid System in the Formalin Test of Persistent Pain in the Rat." European Journal of Pharmacology, vol. 396, no. 2-3, 2000, pp. 85-92.
Beaulieu1 P, Bisogno1 T, Punwar S, et al. Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat. Eur J Pharmacol. 2000;396(2-3):85-92.
Beaulieu1, P., Bisogno1, T., Punwar, S., Farquhar-Smith, W. P., Ambrosino, G., Di Marzo, V., & Rice, A. S. (2000). Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat. European Journal of Pharmacology, 396(2-3), 85-92.
Beaulieu1 P, et al. Role of the Endogenous Cannabinoid System in the Formalin Test of Persistent Pain in the Rat. Eur J Pharmacol. 2000 May 19;396(2-3):85-92. PubMed PMID: 10822060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the endogenous cannabinoid system in the formalin test of persistent pain in the rat. AU - Beaulieu1,P, AU - Bisogno1,T, AU - Punwar,S, AU - Farquhar-Smith,W P, AU - Ambrosino,G, AU - Di Marzo,V, AU - Rice,A S, PY - 2000/5/24/pubmed PY - 2000/7/8/medline PY - 2000/5/24/entrez SP - 85 EP - 92 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 396 IS - 2-3 N2 - It has been suggested that administration of a cannabinoid CB(1) (SR141716A ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide) and CB(2) (SR144528 ¿N-[(1S)-endo-1, 3, 3-trimethyl bicyclo ¿2.2.1 heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyr azo le- 3-carboxamide¿) receptor antagonists to mice potentiates inflammatory hyperalgesia by removing an endogenous cannabinoid tone. We examined whether the behavioural response to s.c. formalin injection in rats is similarly enhanced. A total of 30 animals received SR141716A (0.5 or 5 mg/kg) or SR144528 (0.3 or 3 mg/kg) 30 min before 1% formalin. Pain behaviour was quantified using the composite weighted pain score technique (CPS-WST(0,1,2)). An overall CPS-WST(0,1,2) was calculated for each phase and groups were compared (analysis of variance). The results obtained in the control group confirmed the characteristic biphasic behavioural response to formalin injection. None of antagonist groups had a significant increase in overall CPS-WST(0,1,2) compared to the control. Indeed, a significant decrease in CPS-WST(0,1,2) scores for both phases was detected in most of all of the groups, except SR141716A at 5 mg/kg. Levels of endogenous cannabinoids (anandamide, palmitoylethanolamide, 2-arachidonylglycerol) were measured from rats hind-paw skin 1 h after s.c. injection of 0.9% saline (100 microl), 1% (50 microl), 2. 5% (50 microl) and 5% (100 microl) formalin. The concentration of endocannabinoids did not differ between control and formalin-induced inflammation groups. The activity of anandamide amidohydrolase in hind-paw skin also did not change after treatment with formalin. In conclusion, cannabinoid antagonists do not enhance formalin-evoked pain behaviour. These results suggest that, in this model, endogenous cannabinoids do not tonically attenuate inflammatory hyperalgesia. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/10822060/Role_of_the_endogenous_cannabinoid_system_in_the_formalin_test_of_persistent_pain_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299900002260 DB - PRIME DP - Unbound Medicine ER -