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Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.

Guasti L, Richardson D, Jhaveri M, Eldeeb K, Barrett D, Elphick MR, Alexander SP, Kendall D, Michael GJ, Chapman V - Mol Pain (2009)

Bottom Line: Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro.Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord.Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, UK. l.guasti@qmul.ac.uk

ABSTRACT
Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states.

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Effects of chronic intraperitoneal dosing of minocycline (Mino, 30 mg/kg) or vehicle (Veh, sterile water) on the levels of endocannabinoids (A, B) and related fatty acid ethanolamides (C, D) in the ipsilateral spinal cord of spinal nerve ligated (SNL) or sham-operated rats. Data were analysed using Mann-Whitney nonparametric test and are expressed as a mean percentage of contralateral levels ± SEM (n = 5 – 6 rats/group). * P < 0.05, ** P < 0.01 vs contralateral paw. AEA, anandamide; 2-AG, 2-arachidonoylglycerol; PEA, N-palmitoylethanolamine; OEA, N-oleoylethanolamine.
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Figure 3: Effects of chronic intraperitoneal dosing of minocycline (Mino, 30 mg/kg) or vehicle (Veh, sterile water) on the levels of endocannabinoids (A, B) and related fatty acid ethanolamides (C, D) in the ipsilateral spinal cord of spinal nerve ligated (SNL) or sham-operated rats. Data were analysed using Mann-Whitney nonparametric test and are expressed as a mean percentage of contralateral levels ± SEM (n = 5 – 6 rats/group). * P < 0.05, ** P < 0.01 vs contralateral paw. AEA, anandamide; 2-AG, 2-arachidonoylglycerol; PEA, N-palmitoylethanolamine; OEA, N-oleoylethanolamine.

Mentions: In SNL rats with chronic vehicle treatment, levels of AEA were significantly increased (P < 0.01) in the ipsilateral spinal cord, compared to the contralateral spinal cord (Table 1). Following chronic minocycline treatment in SNL rats, levels of AEA in the ipsilateral spinal cord were also elevated, compared to the contralateral spinal cord (Fig 3). The elevated ipsilateral levels of AEA in minocycline-treated rats were not different from the levels in vehicle-treated SNL rats.


Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.

Guasti L, Richardson D, Jhaveri M, Eldeeb K, Barrett D, Elphick MR, Alexander SP, Kendall D, Michael GJ, Chapman V - Mol Pain (2009)

Effects of chronic intraperitoneal dosing of minocycline (Mino, 30 mg/kg) or vehicle (Veh, sterile water) on the levels of endocannabinoids (A, B) and related fatty acid ethanolamides (C, D) in the ipsilateral spinal cord of spinal nerve ligated (SNL) or sham-operated rats. Data were analysed using Mann-Whitney nonparametric test and are expressed as a mean percentage of contralateral levels ± SEM (n = 5 – 6 rats/group). * P < 0.05, ** P < 0.01 vs contralateral paw. AEA, anandamide; 2-AG, 2-arachidonoylglycerol; PEA, N-palmitoylethanolamine; OEA, N-oleoylethanolamine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719614&req=5

Figure 3: Effects of chronic intraperitoneal dosing of minocycline (Mino, 30 mg/kg) or vehicle (Veh, sterile water) on the levels of endocannabinoids (A, B) and related fatty acid ethanolamides (C, D) in the ipsilateral spinal cord of spinal nerve ligated (SNL) or sham-operated rats. Data were analysed using Mann-Whitney nonparametric test and are expressed as a mean percentage of contralateral levels ± SEM (n = 5 – 6 rats/group). * P < 0.05, ** P < 0.01 vs contralateral paw. AEA, anandamide; 2-AG, 2-arachidonoylglycerol; PEA, N-palmitoylethanolamine; OEA, N-oleoylethanolamine.
Mentions: In SNL rats with chronic vehicle treatment, levels of AEA were significantly increased (P < 0.01) in the ipsilateral spinal cord, compared to the contralateral spinal cord (Table 1). Following chronic minocycline treatment in SNL rats, levels of AEA in the ipsilateral spinal cord were also elevated, compared to the contralateral spinal cord (Fig 3). The elevated ipsilateral levels of AEA in minocycline-treated rats were not different from the levels in vehicle-treated SNL rats.

Bottom Line: Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro.Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord.Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, UK. l.guasti@qmul.ac.uk

ABSTRACT
Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states.

Show MeSH
Related in: MedlinePlus