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Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation.

Lee S, Zhao YQ, Ribeiro-da-Silva A, Zhang J - Mol Pain (2010)

Bottom Line: However, LPS induced microglial activation did not specifically occur along the pain signaling pathway.In contrast, CFA injection led to minor microglial morphological changes and an induction of IκB-α mRNA in the CVO regions; a significant increase in IL-1β and IL-6 mRNA started only at 48 hours post-injection, when the induced pain-related behavior started to resolve.Our detailed analysis of CNS glial response clearly revealed that both nerve injury and oro-facial infection/inflammation induced CNS glial activation, but in a completely different pattern, which suggests a remarkable plasticity of glial cells in response to dynamic changes in their microenvironment and different potential involvement of this non-neuronal cell population in pathological pain development.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Alan Edwards Centre for Research on Pain, McGill University, 740, Dr, Penfield Ave, Montreal, Quebec, H3A 2B2, Canada.

ABSTRACT
Oro-facial pain following injury and infection is frequently observed in dental clinics. While neuropathic pain evoked by injury associated with nerve lesion has an involvement of glia/immune cells, inflammatory hyperalgesia has an exaggerated sensitization mediated by local and circulating immune mediators. To better understand the contribution of central nervous system (CNS) glial cells in these different pathological conditions, in this study we sought to characterize functional phenotypes of glial cells in response to trigeminal nerve injury (loose ligation of the mental branch), infection (subcutaneous injection of lipopolysaccharide--LPS) and to sterile inflammation (subcutaneous injection of complete Freund's adjuvant--CFA) on the lower lip. Each of the three insults triggered a specific pattern of mechanical allodynia. In parallel with changes in sensory response, CNS glial cells reacted distinctively to the challenges. Following ligation of the mental nerve, both microglia and astrocytes in the trigeminal nuclear complex were highly activated, more prominent in the principal sensory nucleus (Pr5) and subnucleus caudalis (Sp5C) area. Microglial response was initiated early (days 3-14), followed by delayed astrocytes activation (days 7-28). Although the temporal profile of microglial and astrocyte reaction corresponded respectively to the initiation and chronic stage of neuropathic pain, these activated glial cells exhibited a low profile of cytokine expression. Local injection of LPS in the lower lip skin also triggered a microglial reaction in the brain, which started in the circumventricular organs (CVOs) at 5 hours post-injection and diffused progressively into the brain parenchyma at 48 hours. This LPS-induced microglial reaction was accompanied by a robust induction of IκB-α mRNA and pro-inflammatory cytokines within the CVOs. However, LPS induced microglial activation did not specifically occur along the pain signaling pathway. In contrast, CFA injection led to minor microglial morphological changes and an induction of IκB-α mRNA in the CVO regions; a significant increase in IL-1β and IL-6 mRNA started only at 48 hours post-injection, when the induced pain-related behavior started to resolve. Our detailed analysis of CNS glial response clearly revealed that both nerve injury and oro-facial infection/inflammation induced CNS glial activation, but in a completely different pattern, which suggests a remarkable plasticity of glial cells in response to dynamic changes in their microenvironment and different potential involvement of this non-neuronal cell population in pathological pain development.

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Astrocyte reaction in response to mental nerve ligation at 14 days post-injury. A). Immunostaining for GFAP in four trigeminal subnuclei, including the principal sensory nucleus (Pr5), spinal oralis (Sp5O), spinal interpolaris (Sp5I) and spinal caudalis (Sp5C). There was a significant increase in GFAP immunoreactivity in nerve injured rats, which was more prominent in Pr5 and Sp5C, together with remarkable changes in astrocyte cell shape (inserts). Note there are no significant changes of GFAP staining in medullar CVOs, area postrema (AP). Diagrams were adapted and modified from [59]. Orange shadowed area indicated where the pictures were taken. Scale bar: 50 μm. B). The density of GFAP+ cells in Pr5 and Sp5C areas was significant higher in injured group than that of sham-operated. Data are expressed as Mean ± SEM. ### P < 0.001, compared to sham-operated group.
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Figure 3: Astrocyte reaction in response to mental nerve ligation at 14 days post-injury. A). Immunostaining for GFAP in four trigeminal subnuclei, including the principal sensory nucleus (Pr5), spinal oralis (Sp5O), spinal interpolaris (Sp5I) and spinal caudalis (Sp5C). There was a significant increase in GFAP immunoreactivity in nerve injured rats, which was more prominent in Pr5 and Sp5C, together with remarkable changes in astrocyte cell shape (inserts). Note there are no significant changes of GFAP staining in medullar CVOs, area postrema (AP). Diagrams were adapted and modified from [59]. Orange shadowed area indicated where the pictures were taken. Scale bar: 50 μm. B). The density of GFAP+ cells in Pr5 and Sp5C areas was significant higher in injured group than that of sham-operated. Data are expressed as Mean ± SEM. ### P < 0.001, compared to sham-operated group.

Mentions: All data are presented as means ± SEM. Statistic significance was determined using: 1) Two way ANOVA analysis for behavioural data in Figure 1; 2) unpaired t-test for the difference of cell numbers between injured- and sham-operated group in Figure 2 and Figure 3; and unpaired t-test for the difference of cytokine expression in each challenged group vs. naive in Figure 10. The criterion for statistical significance was p < 0.05.


Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation.

Lee S, Zhao YQ, Ribeiro-da-Silva A, Zhang J - Mol Pain (2010)

Astrocyte reaction in response to mental nerve ligation at 14 days post-injury. A). Immunostaining for GFAP in four trigeminal subnuclei, including the principal sensory nucleus (Pr5), spinal oralis (Sp5O), spinal interpolaris (Sp5I) and spinal caudalis (Sp5C). There was a significant increase in GFAP immunoreactivity in nerve injured rats, which was more prominent in Pr5 and Sp5C, together with remarkable changes in astrocyte cell shape (inserts). Note there are no significant changes of GFAP staining in medullar CVOs, area postrema (AP). Diagrams were adapted and modified from [59]. Orange shadowed area indicated where the pictures were taken. Scale bar: 50 μm. B). The density of GFAP+ cells in Pr5 and Sp5C areas was significant higher in injured group than that of sham-operated. Data are expressed as Mean ± SEM. ### P < 0.001, compared to sham-operated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992508&req=5

Figure 3: Astrocyte reaction in response to mental nerve ligation at 14 days post-injury. A). Immunostaining for GFAP in four trigeminal subnuclei, including the principal sensory nucleus (Pr5), spinal oralis (Sp5O), spinal interpolaris (Sp5I) and spinal caudalis (Sp5C). There was a significant increase in GFAP immunoreactivity in nerve injured rats, which was more prominent in Pr5 and Sp5C, together with remarkable changes in astrocyte cell shape (inserts). Note there are no significant changes of GFAP staining in medullar CVOs, area postrema (AP). Diagrams were adapted and modified from [59]. Orange shadowed area indicated where the pictures were taken. Scale bar: 50 μm. B). The density of GFAP+ cells in Pr5 and Sp5C areas was significant higher in injured group than that of sham-operated. Data are expressed as Mean ± SEM. ### P < 0.001, compared to sham-operated group.
Mentions: All data are presented as means ± SEM. Statistic significance was determined using: 1) Two way ANOVA analysis for behavioural data in Figure 1; 2) unpaired t-test for the difference of cell numbers between injured- and sham-operated group in Figure 2 and Figure 3; and unpaired t-test for the difference of cytokine expression in each challenged group vs. naive in Figure 10. The criterion for statistical significance was p < 0.05.

Bottom Line: However, LPS induced microglial activation did not specifically occur along the pain signaling pathway.In contrast, CFA injection led to minor microglial morphological changes and an induction of IκB-α mRNA in the CVO regions; a significant increase in IL-1β and IL-6 mRNA started only at 48 hours post-injection, when the induced pain-related behavior started to resolve.Our detailed analysis of CNS glial response clearly revealed that both nerve injury and oro-facial infection/inflammation induced CNS glial activation, but in a completely different pattern, which suggests a remarkable plasticity of glial cells in response to dynamic changes in their microenvironment and different potential involvement of this non-neuronal cell population in pathological pain development.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Alan Edwards Centre for Research on Pain, McGill University, 740, Dr, Penfield Ave, Montreal, Quebec, H3A 2B2, Canada.

ABSTRACT
Oro-facial pain following injury and infection is frequently observed in dental clinics. While neuropathic pain evoked by injury associated with nerve lesion has an involvement of glia/immune cells, inflammatory hyperalgesia has an exaggerated sensitization mediated by local and circulating immune mediators. To better understand the contribution of central nervous system (CNS) glial cells in these different pathological conditions, in this study we sought to characterize functional phenotypes of glial cells in response to trigeminal nerve injury (loose ligation of the mental branch), infection (subcutaneous injection of lipopolysaccharide--LPS) and to sterile inflammation (subcutaneous injection of complete Freund's adjuvant--CFA) on the lower lip. Each of the three insults triggered a specific pattern of mechanical allodynia. In parallel with changes in sensory response, CNS glial cells reacted distinctively to the challenges. Following ligation of the mental nerve, both microglia and astrocytes in the trigeminal nuclear complex were highly activated, more prominent in the principal sensory nucleus (Pr5) and subnucleus caudalis (Sp5C) area. Microglial response was initiated early (days 3-14), followed by delayed astrocytes activation (days 7-28). Although the temporal profile of microglial and astrocyte reaction corresponded respectively to the initiation and chronic stage of neuropathic pain, these activated glial cells exhibited a low profile of cytokine expression. Local injection of LPS in the lower lip skin also triggered a microglial reaction in the brain, which started in the circumventricular organs (CVOs) at 5 hours post-injection and diffused progressively into the brain parenchyma at 48 hours. This LPS-induced microglial reaction was accompanied by a robust induction of IκB-α mRNA and pro-inflammatory cytokines within the CVOs. However, LPS induced microglial activation did not specifically occur along the pain signaling pathway. In contrast, CFA injection led to minor microglial morphological changes and an induction of IκB-α mRNA in the CVO regions; a significant increase in IL-1β and IL-6 mRNA started only at 48 hours post-injection, when the induced pain-related behavior started to resolve. Our detailed analysis of CNS glial response clearly revealed that both nerve injury and oro-facial infection/inflammation induced CNS glial activation, but in a completely different pattern, which suggests a remarkable plasticity of glial cells in response to dynamic changes in their microenvironment and different potential involvement of this non-neuronal cell population in pathological pain development.

Show MeSH
Related in: MedlinePlus