We explored the molecular and behavioral effects of a perineural
Lipopolysaccharide (LPS)-mediated inflammatory priming on the development and maintenance of painful post-
traumatic trigeminal neuropathy (PPTTN) following infra-orbital nerve chronic constriction injury (CCI-IoN) in rats. Rats were pretreated with repetitive perineural
injections in the vicinity of the IoN of either LPS or vehicle (Vhcl) before being submitted to CCI-IoN.
Orofacial pain-like behaviors (response to Von Frey Filament testing and spontaneous isolated face grooming) were measured during the period of LPS
injections (three weeks) and following CCI-IoN surgery (two weeks). Local LPS administration induced an early
pain-like behavior (i.e. an increase in spontaneous
pain [SP] or mechanical static
allodynia [MSA]) in both conditions, and following CCI-IoN, MSA and SP developed earlier and more severely in LPS-pretreated rats than in the control group. Ipsilateral increases of key
neuropathic pain mRNA markers in the IoN parenchyma, trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) were observed in CCI-IoN injured animals as compared to controls. Although no significant molecular differences could be observed within the IoN parenchyma between LPS and Vhcl-pretreated animals, a significant increase of key inflammatory
cytokine Interleukin 1 beta (IL - 1β) could be found in the TG of LPS-pretreated CCI-injured animals versus controls. Finally, a higher increase of
inducible nitric oxide synthase (iNOS) in ipsilateral Sp5C of LPS-pretreated animals was observed as compared to Sp5C of Vhcl-pretreated animals. These results suggest a key role of inflammatory priming in the development and maintenance of PPTTN implicating IL-1β/iNOS-dependent central sensitization mechanisms.