Analgesic and Antiinflammatory Effects of Cannabinoid Receptor Agonists in a Rat Model of Neuropathic Pain

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2009 Jan 20

PMID 19152053

Citations 18

Authors

Anna Leichsenring

Michael Andriske

Ingo Backer

Christine C Stichel

Hermann Lubbert

Affiliations

Soon will be listed here.

Abstract

Cannabinoid receptor (CB) agonists are known to attenuate allodynia in a range of pain models, but their long-term effects and their mechanisms of action are controversial. The present study compares the antiallodynic effects of long-term treatment with a mixed CB1/CB2 (WIN55,212-2) and a selective CB2 (GW405833) cannabinoid receptor agonist and correlates these effects with their influences on spinal cord (SC) glial activation. The substances were applied daily in a rat neuropathic pain model. Tactile allodynia was assessed, and the development of gliosis was illustrated with immunohistochemical methods. Both substances reduced mechanical allodynia. Their analgesic effect was accompanied by a significant reduction in reactive gliosis and cathepsins (CAT) X and S expression. A daily injection of either substance for 8 days was sufficient to induce a sustained antiallodynic effect, which persisted up to 6 days after the last injection. The re-appearance of mechanical allodynia after this period was associated with a breakout of a strong gliotic response in the lumbar SC. Our results emphasize the therapeutic efficacy of cannabinoid receptor agonists and their inhibitory effects on the formation of gliosis.

Citing Articles

L. Extract Alleviates Neuropathic Pain and Modulates CB1 and CB2 Receptor Expression in Rat.

Bartkowiak-Wieczorek J, Bienert A, Czora-Poczwardowska K, Kujawski R, Szulc M, Mikolajczak P Biomolecules. 2024; 14(9).

PMID: 39334832 PMC: 11430414. DOI: 10.3390/biom14091065.

Linderane Attenuates Complete Freund's Adjuvant-Induced Pain and Anxiety in Mice by Restoring Anterior Cingulate Cortex Microglia M2 Polarization through Activating Cannabinoid 2 Receptor.

Chen Y, Qin Y, Gao Y, Wang S, Wang Q, Tang X ACS Pharmacol Transl Sci. 2024; 7(3):797-808.

PMID: 38481693 PMC: 10928880. DOI: 10.1021/acsptsci.3c00321.

The Selective CB2 Agonist COR167 Reduced Symptoms in a Mice Model of Trauma-Induced Peripheral Neuropathy through HDAC-1 Inhibition.

Borgonetti V, Mugnaini C, Corelli F, Galeotti N Biomedicines. 2023; 11(6).

PMID: 37371642 PMC: 10295062. DOI: 10.3390/biomedicines11061546.

Microglial Cannabinoid CB Receptors in Pain Modulation.

Xu K, Wu Y, Tian Z, Xu Y, Wu C, Wang Z Int J Mol Sci. 2023; 24(3).

PMID: 36768668 PMC: 9917135. DOI: 10.3390/ijms24032348.

Behavioral, biochemical and histopathological toxic profiles induced by sub-chronic cannabimimetic WIN55, 212-2 administration in mice.

Omran G, Abd Allah E, Mohammed S, Shehaby D BMC Pharmacol Toxicol. 2023; 24(1):8.

PMID: 36750905 PMC: 9906926. DOI: 10.1186/s40360-023-00644-3.

References

Elmes S, Jhaveri M, Smart D, Kendall D, Chapman V . Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naïve rats and in rat models of inflammatory and neuropathic pain. Eur J Neurosci. 2004; 20(9):2311-20. DOI: 10.1111/j.1460-9568.2004.03690.x. View

Kim S, Chung J . An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992; 50(3):355-363. DOI: 10.1016/0304-3959(92)90041-9. View

Matsuda L, Bonner T, Lolait S . Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol. 1993; 327(4):535-50. DOI: 10.1002/cne.903270406. View

Sagar D, Kelly S, Millns P, OShaughnessey C, Kendall D, Chapman V . Inhibitory effects of CB1 and CB2 receptor agonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats. Eur J Neurosci. 2005; 22(2):371-9. DOI: 10.1111/j.1460-9568.2005.04206.x. View

Herkenham M, Lynn A, Little M, Johnson M, Melvin L, De Costa B . Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A. 1990; 87(5):1932-6. PMC: 53598. DOI: 10.1073/pnas.87.5.1932. View

McMahon S, Cafferty W, Marchand F . Immune and glial cell factors as pain mediators and modulators. Exp Neurol. 2005; 192(2):444-62. DOI: 10.1016/j.expneurol.2004.11.001. View

Valenzano K, Tafesse L, Lee G, Harrison J, Boulet J, Gottshall S . Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology. 2005; 48(5):658-72. DOI: 10.1016/j.neuropharm.2004.12.008. View

Pacher P, Batkai S, Kunos G . The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006; 58(3):389-462. PMC: 2241751. DOI: 10.1124/pr.58.3.2. View

Fox A, Kesingland A, Gentry C, McNair K, Patel S, Urban L . The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain. 2001; 92(1-2):91-100. DOI: 10.1016/s0304-3959(00)00474-7. View

10.

Stella N . Cannabinoid signaling in glial cells. Glia. 2004; 48(4):267-77. DOI: 10.1002/glia.20084. View

11.

Guindon J, Hohmann A . Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. Br J Pharmacol. 2007; 153(2):319-34. PMC: 2219541. DOI: 10.1038/sj.bjp.0707531. View

12.

Watkins L, Hutchinson M, Ledeboer A, Wieseler-Frank J, Milligan E, Maier S . Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids. Brain Behav Immun. 2006; 21(2):131-46. PMC: 1857294. DOI: 10.1016/j.bbi.2006.10.011. View

13.

Ashton C . Adverse effects of cannabis and cannabinoids. Br J Anaesth. 2000; 83(4):637-49. DOI: 10.1093/bja/83.4.637. View

14.

Parolaro D . Presence and functional regulation of cannabinoid receptors in immune cells. Life Sci. 1999; 65(6-7):637-44. DOI: 10.1016/s0024-3205(99)00286-6. View

15.

Bridges D, Ahmad K, Rice A . The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain. Br J Pharmacol. 2001; 133(4):586-94. PMC: 1572814. DOI: 10.1038/sj.bjp.0704110. View

16.

Beaulieu P, Ware M . Reassessment of the role of cannabinoids in the management of pain. Curr Opin Anaesthesiol. 2007; 20(5):473-7. DOI: 10.1097/ACO.0b013e3282efd175. View

17.

Lever I, Rice A . Cannabinoids and pain. Handb Exp Pharmacol. 2006; (177):265-306. DOI: 10.1007/978-3-540-33823-9_10. View

18.

Marchalant Y, Rosi S, Wenk G . Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent model of chronic brain inflammation. Neuroscience. 2006; 144(4):1516-22. PMC: 1852513. DOI: 10.1016/j.neuroscience.2006.11.016. View

19.

Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G . Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci. 2003; 23(4):1398-405. PMC: 6742252. View

20.

De Vry J, Kuhl E, Franken-Kunkel P, Eckel G . Pharmacological characterization of the chronic constriction injury model of neuropathic pain. Eur J Pharmacol. 2004; 491(2-3):137-48. DOI: 10.1016/j.ejphar.2004.03.051. View