engleski

Lidocaine injection into the Sprague-Dawley rat dorsal root ganglion causes neuroinflammation and pain-related behavior

Background & Aims: Injury of a spinal nerve or dorsal root ganglion (DRG) during selective spinal nerve blocks (SSNB) 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: All experimental protocols were approved by the Ethics Committee of the University of Split, School of Medicine. A total of 56 Sprague-Dawley rats weighing 150-200 g were used. Rats underwent minimal laminectomy and injection of 4 uL lidocaine into the L5 spinal nerve or L5 DRG. The control group received injection of 0.9% NaCl. The injections were made using a 29-gauge needle with a slightly bent beveled tip. We performed extensive methodological research regarding targeted delivery of substances into the DRGs because of the various methods reported in the literature. The DRG injection following minimal laminectomy proved to be the most successful approach in terms of precision. Before and after surgery, behavioral testing was performed to determine the response to nociceptive mechanical stimulation of the rat paw. DRGs were harvested, stained, and rings of immunoreactive satellite cells around neurons were counted. We did not try to superfuse the DRGs with non-invasive methods. 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 GFAP immunopositive glial cell rings, which represent an activation of satellite cells, significantly increased in DRGs after injection of lidocaine into either the DRG or the spinal nerve. 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 is producing hyperalgesia, possibly as a consequence of an early neurinflammation that will later become evident through activation of resident satellite glial cells. In addition, we showed that the optimal method for targeted DRG delivery in the rat was injection after minimal laminectomy, which may be useful for further animal studies. The clinical implications are that an effort should be made to minimize risk of neural injuries while performing SSNBs. Acknowledgments: Supported by the Croatian Ministry of Science, Education and Sports (grant No. 216-2160528-0522).

lidocaine; rat; dorsal root ganglion; neuroinflammation; pain

nije evidentirano