Tags

Type your tag names separated by a space and hit enter

Peripheral antinociceptive effect of anandamide and drugs that affect the endocannabinoid system on the formalin test in normal and streptozotocin-diabetic rats.
Neuropharmacology. 2012 Dec; 63(8):1286-97.N

Abstract

Diabetes is often associated with painful neuropathy. The current treatments are symptomatic and ineffective. Cannabinoids have been proposed as promising drugs for chronic pain treatment and its antinociceptive effect has already been related in nerve injury models of neuropathic pain, but little has been investigated in painful diabetic neuropathy models. Thus, the current study aims to investigate the potential antinociceptive effect of drugs that alter endocannabinoid system when injected subcutaneously into the dorsal surface of the ipsilateral hind paw in chemical hyperalgesia induced by formalin in both normoglycemic (Ngl) and streptozotocin-diabetic (Dbt) rats. Diabetic rats exhibited exaggerated flinching behaviors during first and second phases of the formalin test, indicating the presence of hyperalgesia. AM404, an anandamide (AEA) re-uptake inhibitor, AEA (an agonist of CB1/CB2 receptors) or ACEA (a selective CB1 receptor agonist) induced antinociception in both phases of formalin test in Ngl and Dbt rats. In both groups, the antinociceptive effect of ACEA was prevented by AM251, a CB1 inverse agonist while the antinociceptive effect of AEA was prevented by AM251 or AM630, a CB2 receptor antagonist. In Ngl rats, the antinociceptive effect of AM404 was prevented by AM251 or capsazepine only during first phase of the formalin test while in Dbt rats, this effect was blocked by pretreatment with AM251 (both phases) or AM630 (second phase). Taken together, these results demonstrated broad-spectrum antinociceptive properties of cannabinoids in a model of painful diabetic neuropathy. Peripheral activation of both cannabinoid receptors seems to mediate the antinociceptive effect of exogenous or endogenous anandamide.

Authors+Show Affiliations

Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Curitiba 81540-990, PR, Brazil.No 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

22959964

Citation

Schreiber, Anne K., et al. "Peripheral Antinociceptive Effect of Anandamide and Drugs That Affect the Endocannabinoid System On the Formalin Test in Normal and Streptozotocin-diabetic Rats." Neuropharmacology, vol. 63, no. 8, 2012, pp. 1286-97.
Schreiber AK, Neufeld M, Jesus CH, et al. Peripheral antinociceptive effect of anandamide and drugs that affect the endocannabinoid system on the formalin test in normal and streptozotocin-diabetic rats. Neuropharmacology. 2012;63(8):1286-97.
Schreiber, A. K., Neufeld, M., Jesus, C. H., & Cunha, J. M. (2012). Peripheral antinociceptive effect of anandamide and drugs that affect the endocannabinoid system on the formalin test in normal and streptozotocin-diabetic rats. Neuropharmacology, 63(8), 1286-97. https://doi.org/10.1016/j.neuropharm.2012.08.009
Schreiber AK, et al. Peripheral Antinociceptive Effect of Anandamide and Drugs That Affect the Endocannabinoid System On the Formalin Test in Normal and Streptozotocin-diabetic Rats. Neuropharmacology. 2012;63(8):1286-97. PubMed PMID: 22959964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peripheral antinociceptive effect of anandamide and drugs that affect the endocannabinoid system on the formalin test in normal and streptozotocin-diabetic rats. AU - Schreiber,Anne K, AU - Neufeld,Manuele, AU - Jesus,Carlos H A, AU - Cunha,Joice M, Y1 - 2012/09/01/ PY - 2012/03/16/received PY - 2012/07/26/revised PY - 2012/08/14/accepted PY - 2012/9/11/entrez PY - 2012/9/11/pubmed PY - 2013/2/21/medline SP - 1286 EP - 97 JF - Neuropharmacology JO - Neuropharmacology VL - 63 IS - 8 N2 - Diabetes is often associated with painful neuropathy. The current treatments are symptomatic and ineffective. Cannabinoids have been proposed as promising drugs for chronic pain treatment and its antinociceptive effect has already been related in nerve injury models of neuropathic pain, but little has been investigated in painful diabetic neuropathy models. Thus, the current study aims to investigate the potential antinociceptive effect of drugs that alter endocannabinoid system when injected subcutaneously into the dorsal surface of the ipsilateral hind paw in chemical hyperalgesia induced by formalin in both normoglycemic (Ngl) and streptozotocin-diabetic (Dbt) rats. Diabetic rats exhibited exaggerated flinching behaviors during first and second phases of the formalin test, indicating the presence of hyperalgesia. AM404, an anandamide (AEA) re-uptake inhibitor, AEA (an agonist of CB1/CB2 receptors) or ACEA (a selective CB1 receptor agonist) induced antinociception in both phases of formalin test in Ngl and Dbt rats. In both groups, the antinociceptive effect of ACEA was prevented by AM251, a CB1 inverse agonist while the antinociceptive effect of AEA was prevented by AM251 or AM630, a CB2 receptor antagonist. In Ngl rats, the antinociceptive effect of AM404 was prevented by AM251 or capsazepine only during first phase of the formalin test while in Dbt rats, this effect was blocked by pretreatment with AM251 (both phases) or AM630 (second phase). Taken together, these results demonstrated broad-spectrum antinociceptive properties of cannabinoids in a model of painful diabetic neuropathy. Peripheral activation of both cannabinoid receptors seems to mediate the antinociceptive effect of exogenous or endogenous anandamide. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/22959964/Peripheral_antinociceptive_effect_of_anandamide_and_drugs_that_affect_the_endocannabinoid_system_on_the_formalin_test_in_normal_and_streptozotocin_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(12)00445-5 DB - PRIME DP - Unbound Medicine ER -