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Eun Joo Choi,1 Dong-Hyun Kim,1 Woong Ki Han,1 Ho-Jin Lee,2 Imhong Kang,3 Francis Sahngun Nahm,1,4 Pyung-Bok Lee1,4 1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Korea; 3Department of Anesthesiology and Pain Medicine, Bundang Chuk Hospital, Seongnam, Korea; 4Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of KoreaCorrespondence: Pyung-Bok LeeDepartment of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro 173 Beon-Gil, Bundang-Gu, Seongnam, 13620, KoreaTel +82-31- 787-7499Fax +82-31- 787-4063Email painfree@snubh.orgPurpose: Particulate steroids used in epidural steroid injections have been suspected as a cause of post-procedural embolic events. Some particulate steroids have been suspended only when the transforaminal approach is used for an epidural block of the spine. In contrast, non-particulate steroids are generally accepted for safety during epidural steroid injections. However, the safety of using a mixture of non-particulate steroids and local anesthetics is unknown. This study analyzed whether mixtures of commonly used non-particulate steroids and local anesthetics form crystals in solution.Methods: We mixed non-particulate steroids (betamethasone sodium phosphate, dexamethasone sodium phosphate, and dexamethasone palmitate) and local anesthetics (ropivacaine, levobupivacaine, bupivacaine, and lidocaine) at different ratios. We used fluorescence microscopy to observe whether crystals formed in mixed solutions; we also measured the pH of each steroid, local anesthetic, and the mixtures.Results: Ropivacaine or levobupivacaine and betamethasone sodium phosphate produced large crystals (> 50 μm). Ropivacaine or levobupivacaine and dexamethasone sodium phosphate produced small crystals (< 10 μm). Lidocaine and all non-particulate steroids produced no identifiable crystals; dexamethasone palmitate and all local anesthetics did not form significant particulates. Betamethasone sodium phosphate and dexamethasone sodium phosphate demonstrated basic pH, while all local anesthetics demonstrated acidic pH. Mixtures showed a wide pH range.Conclusion: Non-particulate steroids can form crystals upon combination with local anesthetics. Crystal formation may be caused by alkalinization of steroids. The mixing of ropivacaine or levobupivacaine and betamethasone sodium phosphate may require caution during an epidural steroid injection. Lidocaine or bupivacaine is recommended as a local anesthetic. Dexamethasone palmitate is a candidate for a mixture, but additional studies on its safety and effectiveness are needed.Keywords: epidural space, injections, lidocaine, local anesthetics, particle size, steroids

Francis Sahngun Nahm,1,2 Sang-Soep Nahm,3 Woong Ki Han,1 Ho Young Gil,4 Eunjoo Choi,1 Pyung Bok Lee1,2 1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; 2College of Medicine, Seoul National University, Seoul, South Korea; 3Laboratory of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 4Department of Anesthesiology and Pain Medicine, Ajou University Hospital, Suwon, South Korea Purpose: Complex regional pain syndrome (CRPS) is a rare but refractory pain disorder. Recent advanced information retrieval studies using text-mining and network analysis have suggested nuclear factor kappa B (NFκB) as a possible central mediator of CRPS. The brain is also known to play important roles in CRPS. The aim of this study was to evaluate changes in cerebral NFκB in rats with CRPS. Materials and methods: The chronic post-ischemia perfusion (CPIP) model was used as the CRPS animal model. O-rings were applied to the left hind paws of the rats. The rats were categorized into three groups according to the results of behavioral tests: the CPIP-positive (A) group, the CPIP-negative (B) group, and the control (C) group. Three weeks after the CPIP procedure, the right cerebrums of the animals were harvested to measure NFkB levels using an ELISA. Results: Animals in group A had significantly decreased mechanical pain thresholds (P