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.