Limits...
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.

Show MeSH

Related in: MedlinePlus

Chronic treatment with minocycline significantly attenuates spinal nerve ligation-induced reduction in mechanical paw withdrawal threshold. Minocycline (Mino, 30 mg/kg, ip) or vehicle (Veh, sterile water) was injected daily for 14 days and paw withdrawal threshold of the ipsilateral (Ipsi) and contralateral (Contra) hindpaw were measured using von Frey filaments (sham data not shown for clarity of figure). Data were analysed using 2-way ANOVA followed by Bonferroni's post-hoc tests, and are expressed as mean (± SEM, n = 6 rats/group). ** P < 0.01, *** P < 0.001 vs contralateral paw; δ P < 0.05, δδ P < 0.01, δδδ P < 0.001 vs vehicle-ipsilateral paw.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2719614&req=5

Figure 1: Chronic treatment with minocycline significantly attenuates spinal nerve ligation-induced reduction in mechanical paw withdrawal threshold. Minocycline (Mino, 30 mg/kg, ip) or vehicle (Veh, sterile water) was injected daily for 14 days and paw withdrawal threshold of the ipsilateral (Ipsi) and contralateral (Contra) hindpaw were measured using von Frey filaments (sham data not shown for clarity of figure). Data were analysed using 2-way ANOVA followed by Bonferroni's post-hoc tests, and are expressed as mean (± SEM, n = 6 rats/group). ** P < 0.01, *** P < 0.001 vs contralateral paw; δ P < 0.05, δδ P < 0.01, δδδ P < 0.001 vs vehicle-ipsilateral paw.

Mentions: Chronic vehicle treatment did not alter the ipsilateral or contralateral paw withdrawal thresholds (PWTs) in sham-operated rats (data not shown). By contrast, SNL rats chronically treated with vehicle had a significantly (P < 0.001) lower ipsilateral PWT, compared to the PWT of the contralateral hindpaw of SNL rats and ipsilateral hindpaw of sham-operated rats (data not shown), consistent with the development of mechanical allodynia in these rats (Fig 1). Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) starting at 1 hr before SNL surgery significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-surgery compared to vehicle-treated SNL rats (Fig 1). Chronic minocycline treatment (30 mg/kg, ip) in sham-operated rats did not alter ipsilateral or contralateral PWT (data not shown).


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)

Chronic treatment with minocycline significantly attenuates spinal nerve ligation-induced reduction in mechanical paw withdrawal threshold. Minocycline (Mino, 30 mg/kg, ip) or vehicle (Veh, sterile water) was injected daily for 14 days and paw withdrawal threshold of the ipsilateral (Ipsi) and contralateral (Contra) hindpaw were measured using von Frey filaments (sham data not shown for clarity of figure). Data were analysed using 2-way ANOVA followed by Bonferroni's post-hoc tests, and are expressed as mean (± SEM, n = 6 rats/group). ** P < 0.01, *** P < 0.001 vs contralateral paw; δ P < 0.05, δδ P < 0.01, δδδ P < 0.001 vs vehicle-ipsilateral paw.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Chronic treatment with minocycline significantly attenuates spinal nerve ligation-induced reduction in mechanical paw withdrawal threshold. Minocycline (Mino, 30 mg/kg, ip) or vehicle (Veh, sterile water) was injected daily for 14 days and paw withdrawal threshold of the ipsilateral (Ipsi) and contralateral (Contra) hindpaw were measured using von Frey filaments (sham data not shown for clarity of figure). Data were analysed using 2-way ANOVA followed by Bonferroni's post-hoc tests, and are expressed as mean (± SEM, n = 6 rats/group). ** P < 0.01, *** P < 0.001 vs contralateral paw; δ P < 0.05, δδ P < 0.01, δδδ P < 0.001 vs vehicle-ipsilateral paw.
Mentions: Chronic vehicle treatment did not alter the ipsilateral or contralateral paw withdrawal thresholds (PWTs) in sham-operated rats (data not shown). By contrast, SNL rats chronically treated with vehicle had a significantly (P < 0.001) lower ipsilateral PWT, compared to the PWT of the contralateral hindpaw of SNL rats and ipsilateral hindpaw of sham-operated rats (data not shown), consistent with the development of mechanical allodynia in these rats (Fig 1). Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) starting at 1 hr before SNL surgery significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-surgery compared to vehicle-treated SNL rats (Fig 1). Chronic minocycline treatment (30 mg/kg, ip) in sham-operated rats did not alter ipsilateral or contralateral PWT (data not shown).

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