Abstract
Varicella zoster virus (VZV) infects the face and can result in chronic, debilitating pain. The mechanism for this pain is unknown and current treatment is often not effective, thus investigations into the pain pathway become vital. Pain itself is multidimensional, consisting of sensory and affective experiences. One of the primary brain substrates for transmitting sensory signals in the face is the ventral posterior medial/posterior lateral thalamus (VPM/VPL). In addition, the anterior cingulate cortex (ACC) has been shown to be vital in the affective experience of pain, so investigating both of these areas in freely behaving animals was completed to address the role of the brain in VZV-induced pain. Our lab has developed a place escape avoidance paradigm (PEAP) to measure VZV-induced affective pain in the orofacial region of the rat. Using this assay as a measure of the affective pain experience a significant response was observed after VZV injection into the whisker pad and after VZV infusion into the trigeminal ganglion. Local field potentials (LFPs) are the summed electrical current from a group of neurons. LFP in both the VPM/VPL and ACC was attenuated in VZV injected rats after inhibition of neuronal activity. This inhibition of VPM/VPL neurons was accomplished using a designer receptor exclusively activated by a designer drug (DREADD). Immunostaining showed that cells within the VPM/VPL expressed thalamic glutamatergic vesicle transporter-2, NeuN and DREADD suggesting inhibition occurred primarily in excitable neurons. From these results we conclude: (1) that VZV associated pain does not involve a mechanism exclusive to the peripheral nerve terminals, and (2) can be controlled, in part, by excitatory neurons within the VPM/VPL that potentially modulate the affective experience by altering activity in the ACC.
Highlights
Varicella zoster virus (VZV) causes chickenpox and shingles resulting in acute and chronic pain
Knowing that peripheral neurites show damage it was necessary to determine if the mechanism for VZV pain had an exclusive origin in the peripheral nerve. We address this question by measuring affective pain responses following infusion of VZV directly into the trigeminal ganglion and circumventing peripheral nerve terminal infection
Neurite retraction within the whisker pad and paw can be observed after VZV injection (Guedon et al, 2015; Stinson et al, 2017), consistent with humans that have VZV-induced neuralgia (Guedon et al, 2015)
Summary
Varicella zoster virus (VZV) causes chickenpox and shingles resulting in acute and chronic pain. Orofacial zoster and post-herpetic neuralgia is common in the facial region, with greater than 13% of HZ cases having facial involvement (Ragozzino et al, 1982; Pavan-Langston, 1995; Pevenstein et al, 1999) This includes HZ opthalmicus (HZO), in which there is head and facial pain, and ocular pain. To address the role of central processing in VZV-induced pain and to determine if the mechanism for VZV pain is exclusive to the peripheral nerves a place escape avoidance paradigm (PEAP) was used to measure VZV-induced affective pain in the orofacial region of the rat. Immunostaining was completed to identify the cell type controlled by the DREADD constructs These studies were completed to determine a role for the central nervous system in VZV-induced affective pain in an awake animal
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