Longitudinal Tracking of Astrocyte Reactivity During the Development of Chronic Orofacial Neuropathic Pain Using...

Chronic neuropathic pain represents a significant global health burden and is hypothesized to be maintained by an altered astrocyte-neuron interplay. Evidence of astrocyte contributions to neuropathic pain are derived from both post-mortem immunohistochemical analyses and in vivo pharmacological studies. These data cannot provide insights into dynamic changes in astrocytes within an individual as pain develops. Here, we present the first use of [¹⁸F]-SMBT-1, a radioisotope that binds monoamine oxidase-B (MAO-B) in reactive astrocytes, in a longitudinal (35 days) study of the development of orofacial neuropathic pain. We used the chronic constriction injury of the infraorbital nerve (ION-CCI) to produce orofacial neuropathic pain in adult male Sprague-Dawley rats, which we compared to both sham-injury and anesthesia controls. Between 14 and 28 days following ION-CCI, increases in SMBT-1 binding occurred in: the trigeminal nerve, ganglion and the spinal trigeminal nucleus; as well as the nucleus accumbens and dorsal striatum. Increased MAO-B expression in these regions was confirmed using immunohistochemical analysis. MAO-B expression was also confirmed in the ION, the trigeminal ganglion, and trigeminal root entry zone. These data provide evidence of regional and temporally specific increases in astrocyte reactivity, which may be critical for establishing chronic orofacial neuropathic pain. Longitudinal mapping of changes in astrocyte reactivity during the development of chronic orofacial neuropathic pain will provide an opportunity to test the potential of astrocyte specific compounds delivered at specific time points following nerve injury, to determine the key brain regions that could be targeted to prevent and/or reverse the development of chronic neuropathic pain.