The Non-psychoactive Phytocannabinoid Cannabidiol (CBD) Attenuates Pro-inflammatory Mediators, T Cell Infiltration, and Thermal Sensitivity Following Spinal Cord Injury in Mice

Overview

Journal Cell Immunol

Publisher Elsevier

Specialties Allergy & Immunology
Cell Biology

Date 2018 May 23

PMID 29784129

Citations 28

Authors

Hongbo Li

Weimin Kong

Christina R Chambers

Daohai Yu

Doina Ganea

Ronald F Tuma

Sara Jane Ward

Affiliations

Soon will be listed here.

Abstract

We evaluated the effects of the non-psychoactive cannabinoid cannabidiol (CBD) on the inflammatory response and recovery of function following spinal cord injury (SCI). Female C57Bl/6 mice were exposed to spinal cord contusion injury (T9-10) and received vehicle or CBD (1.5 mg/kg IP) injections for 10 weeks following injury. The effect of SCI and CBD treatment on inflammation was assessed via microarray, qRT-PCR and flow cytometry. Locomotor and bladder function and changes in thermal and mechanical hind paw sensitivity were also evaluated. There was a significant decrease in pro-inflammatory cytokines and chemokines associated with T-cell differentiation and invasion in the SCI-CBD group as well as a decrease in T cell invasion into the injured cord. A higher percentage of SCI mice in the vehicle-treated group (SCI-VEH) went on to develop moderate to severe (0-65.9% baseline thermal threshold) thermal sensitivity as compared with CBD-treated (SCI-CBD) mice. CBD did not affect recovery of locomotor or bladder function following SCI. Taken together, CBD treatment attenuated the development of thermal sensitivity following spinal cord injury and this effect may be related to protection against pathological T-cell invasion.

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References

Yezierski P, Liu S, Ruenes L, Kajander J, Brewer L . Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model. Pain. 1998; 75(1):141-155. DOI: 10.1016/S0304-3959(97)00216-9. View

Chang H . Subacute human spinal cord contusion: few lymphocytes and many macrophages. Spinal Cord. 2006; 45(2):174-82. DOI: 10.1038/sj.sc.3101910. View

Adhikary S, Li H, Heller J, Skarica M, Zhang M, Ganea D . Modulation of inflammatory responses by a cannabinoid-2-selective agonist after spinal cord injury. J Neurotrauma. 2011; 28(12):2417-27. PMC: 3235339. DOI: 10.1089/neu.2011.1853. View

Ward S, McAllister S, Kawamura R, Murase R, Neelakantan H, Walker E . Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT(1A) receptors without diminishing nervous system function or chemotherapy efficacy. Br J Pharmacol. 2013; 171(3):636-45. PMC: 3969077. DOI: 10.1111/bph.12439. View

Costigan M, Moss A, Latremoliere A, Johnston C, Verma-Gandhu M, Herbert T . T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci. 2009; 29(46):14415-22. PMC: 2813708. DOI: 10.1523/JNEUROSCI.4569-09.2009. View

Carrier E, Auchampach J, Hillard C . Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A. 2006; 103(20):7895-900. PMC: 1472541. DOI: 10.1073/pnas.0511232103. View

Popovich P, Wei P, Stokes B . Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol. 1997; 377(3):443-64. DOI: 10.1002/(sici)1096-9861(19970120)377:3<443::aid-cne10>3.0.co;2-s. View

Sroga J, Jones T, Kigerl K, McGaughy V, Popovich P . Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol. 2003; 462(2):223-40. DOI: 10.1002/cne.10736. View

Hoschouer E, Yin F, Jakeman L . L1 cell adhesion molecule is essential for the maintenance of hyperalgesia after spinal cord injury. Exp Neurol. 2008; 216(1):22-34. PMC: 3691996. DOI: 10.1016/j.expneurol.2008.10.025. View

10.

Toth C, Jedrzejewski N, Ellis C, Frey 2nd W . Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol Pain. 2010; 6:16. PMC: 2845559. DOI: 10.1186/1744-8069-6-16. View

11.

Murakami T, Kanchiku T, Suzuki H, Imajo Y, Yoshida Y, Nomura H . Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice. Exp Ther Med. 2013; 6(5):1194-1198. PMC: 3820708. DOI: 10.3892/etm.2013.1296. View

12.

Detloff M, Fisher L, McGaughy V, Longbrake E, Popovich P, Basso D . Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol. 2008; 212(2):337-47. PMC: 2600773. DOI: 10.1016/j.expneurol.2008.04.009. View

13.

Chen M, Kress B, Han X, Moll K, Peng W, Ji R . Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury. Glia. 2012; 60(11):1660-70. PMC: 3604747. DOI: 10.1002/glia.22384. View

14.

Kwiatkoski M, Guimaraes F, Del-Bel E . Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury. Neurotox Res. 2011; 21(3):271-80. DOI: 10.1007/s12640-011-9273-8. View

15.

Nesic O, Lee J, Johnson K, Ye Z, Xu G, Unabia G . Transcriptional profiling of spinal cord injury-induced central neuropathic pain. J Neurochem. 2005; 95(4):998-1014. DOI: 10.1111/j.1471-4159.2005.03462.x. View

16.

Gal P, Kravcukova P, Mokry M, Kluchova D . Chemokines as possible targets in modulation of the secondary damage after acute spinal cord injury: a review. Cell Mol Neurobiol. 2009; 29(6-7):1025-35. PMC: 11506275. DOI: 10.1007/s10571-009-9392-4. View

17.

Coleman W, Benzel D, Cahill D, Ducker T, Geisler F, Green B . A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury. J Spinal Disord. 2000; 13(3):185-99. DOI: 10.1097/00002517-200006000-00001. View

18.

Ward S, Ramirez M, Neelakantan H, Walker E . Cannabidiol prevents the development of cold and mechanical allodynia in paclitaxel-treated female C57Bl6 mice. Anesth Analg. 2011; 113(4):947-50. PMC: 3249239. DOI: 10.1213/ANE.0b013e3182283486. View

19.

Qian T, Campagnolo D, Kirshblum S . High-dose methylprednisolone may do more harm for spinal cord injury. Med Hypotheses. 2000; 55(5):452-3. DOI: 10.1054/mehy.2000.1165. View

20.

Booz G . Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011; 51(5):1054-61. PMC: 3085542. DOI: 10.1016/j.freeradbiomed.2011.01.007. View