Lidocaine Injection into the Rat Dorsal Root Ganglion Causes Neuroinflammation

Abstract

BACKGROUND Injury of a spinal nerve or dorsal root ganglion (DRG) during selective spinal nerve blocks is a potentially serious complication that has not been adequately investigated. Our hypothesis was that local anesthetic injection into these structures may result in an inflammatory response and hyperalgesia. METHODS We evaluated inflammatory and behavioral responses after injection of 4 μL lidocaine or saline into the L5 spinal nerve or DRG of rats after partial laminectomy. Behavioral testing was performed before and after surgery to examine hyperalgesia in response to nociceptive mechanical stimulation of the foot. DRGs were harvested and stained, and rings of immunoreactive glial cells around neurons were counted. RESULTS Animals demonstrated hyperalgesia on the ipsilateral paw up to 4 days after lidocaine injection into the DRG but not after injection into the spinal nerve. The number of glial fibrillary acid protein immunopositive glial cell rings, which represent activation of satellite cells, significantly increased in DRGs after injection of lidocaine into either the DRG or the spinal nerve. The number of glial fibrillary acid protein-positive cells in the lidocaine-injected group was significantly larger than in the saline-injected group. Sporadic OX-42 immunopositive cells, which represent activated microglia, were also seen in lidocaine-injected DRGs. Testing for Pan-T expression, which labels activated T lymphocytes, showed no positive cells. CONCLUSIONS Lidocaine injection into the DRG may produce hyperalgesia, possibly due to activation of resident satellite glial cells. In a clinical setting, local anesthetic injection into the DRG should be avoided during selective spinal nerve blocks.

Dorsal root ganglion – a potential new therapeutic target for neuropathic pain

“…In the experimental setting it has been reported that topical application of local anesthetic to the DRG induces mechanical hyperalgesia in the rat,29 but possible morphological changes in the DRG have not been studied. We have found that the injection of lidocaine into a DRG induced pain-related behavior and a marked inflammatory response in the DRG 37. It is important that we also identified an inflammatory response in saline-injected rats, but this was not accompanied with marked hyperalgesia, perhaps because this inflammatory response was significantly lower than after the lidocaine injection suggesting that DRG injection can be a secure procedure 37…”

“…Our group evaluated the neuroinflammatory response following a lidocaine or saline injection into the DRG or the adjacent spinal nerve 37. We hypothesized that an inflammatory response may follow local anesthetic injection into the DRG and produce hyperalgesia.…”

Targeted delivery of pharmacological agents into rat dorsal root ganglion

“…We have also found that injection per se (e.g. saline) into spinal nerve or DRG does not cause neuroinflammation (Puljak et al, in press). Thus, this approach using direct exposure of the DRG offers the greatest accuracy and produces minimal unintended effects.…”

Glial fibrillary acidic protein promoter determines transgene expression in satellite glial cells following intraganglionic adeno‐associated virus delivery in adult rats

“…Quantification of transgene expression in neurons or SGCs was determined as reported previously (Puljak, Kojundzic, Hogan, & Sapunar, ; Yu et al, ). Immunostaining of Tubb3 (a pan‐neuronal marker) and GFAP or GS (SGC markers) was used to distinguish neurons and SGCs, respectively.…”