Changes in Neuroglial Activity in Multiple Spinal Segments after Caudal Epidural Pulsed Radiofrequency in a Rat Model of Lumbar Disc Herniation

Background: Herniated lumbar discs can induce sciatica by mechanical compression and/ or chemical irritation. It was recently reported that neuroglial cellular activity after pulsed radiofrequency (PRF) application to a single dorsal root ganglion (DRG) attenuated neuroglial activity at the corresponding spinal dorsal horn. Recently, caudal epidural PRF has been used to manage neuropathic pain, but evidence of molecular changes after the administration of caudal epidural PRF to attenuate neuropathic pain is lacking, and it has not been determined whether caudal epidural PRF affects neuroglial activity at different spinal levels. Objectives: Using immunohistochemical methods in a rat model of lumbar disc herniation, the authors investigated the effects of caudal epidural PRF administration on pain-related behavior, on the activations of microglia and astrocytes in spinal cord, and on the expressions of calcitonin gene-related peptide (CGRP) and Transient receptor potential vanilloid 1(TRPV1) in the DRG at the L3, L4, L5, L6, and S1 levels. Study Design: Controlled animal trial. Setting: University hospital laboratory. Methods: Forty-five Sprague-Dawley rats were randomly assigned to a sham-operated group (n = 10) or a nucleus pulposus (NP)-exposed group (n = 35). Rats in the NP-exposed group were further subdivided into a NP-exposed with sham stimulation group (the NP-nonPRF group; n = 13) or a NP exposed with caudal epidural PRF stimulation group (the NP-PRF group; n = 22). Pulsed radiofrequency was administered on postoperative day 10 (POD 10) by placing an electrode in the caudal epidural space through the sacral hiatus and administering 5 Hz of PRF current for 600 seconds (maximum tip temperature 42°C). Rats were tested for mechanical allodynia on POD 10 and on days 7 and 14 after caudal epidural PRF administration (post-PRF). At 14 days post-PRF, sections of the spinal cord from L3, L4, L5, L6, and S1 were immunostained for ionized calciumbinding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), and DRGs from the same levels were immunostained for CGRP and TRPV1. Results: Mechanical withdrawal thresholds increased at 7 days post-PRF (P = 0.04), and the immunohistochemical expression of Iba1 in the L5 spinal dorsal horn and of CGRP in the L5 DRG were quantitatively reduced (P < 0.001) at 14 days post-PRF. Furthermore, the upregulations of Iba1 at L3, L4, L6, and S1 dorsal horns and CGRP at L6 DRG were also attenuated by caudal epidural PRF (P < 0.001). Limitation: We examined molecular changes only in ipsilateral lumbar regions and at 14 days post-PRF. Conclusion: Caudal epidural PRF reduced mechanical allodynia and downregulated microglia activity and CGRP expression at the lumbar disc herniated level and in adjacent lumbar spinal levels in a rat model of lumbar disc herniation. Key words: Caudal, pulsed radiofrequency, multisegmental, lumbar disc herniation, microglia, calcitonin gene-related peptide