Abstract:
BACKGROUND:Intrathecal methylprednisolone acetate (MPA) has been used in patients with chronic pain syndromes. Its safety has been debated after reports of adverse events. No systematic preclinical evaluation of MPA has been reported. In the current study, the acute and long-term effects of intrathecal MPA on dog spinal tissue was studied with the injectate reformulated to include minimal adjuvants. METHODS:Seventeen dogs were implanted with intrathecal catheters and randomized to three groups: vehicle (lidocaine; 4 dogs), MPA 20 mg/ml (human dose; 7 dogs), and MPA 80 mg/ml (maximum deliverable dose; 6 dogs). In parallel with the human protocols, dogs received four injections at 7-day intervals. Clinical observations and plasma methylprednisolone measurements were done before and at intervals after intrathecal delivery. One week (acute) or 6 weeks (long-term) after the last injection, animals were sacrificed and spinal tissues harvested for histopathology. RESULTS:Other than a brief motor block, no adverse clinical event occurred in any animal. Group A (vehicle) showed minimal histologic changes (median histology-score; acute: 1.3, long-term: 1.0). Group B (MPA 20 mg/ml) had a diffuse inflammatory reaction (acute: 2.0, long-term: 3.0), group C (MPA 80 mg/ml) a severe inflammatory response, with large inflammatory masses (acute: 4.0, long-term: 7.0) The severity of the inflammatory reaction increased significantly with increasing dose at long-term sacrifice (acute P = 0.167, long-term P = 0.014). No neuronal injury, demyelination, or gliosis was seen in any animal. CONCLUSION:These results, showing dose-dependent intrathecal inflammatory reactions at MPA doses and injectate concentrations comparable to those used in humans, indicate that the continued use of this modality in humans is not recommended.
journal_name
Anesthesiologyjournal_title
Anesthesiologyauthors
Rijsdijk M,van Wijck AJ,Kalkman CJ,Meulenhoff PC,Grafe MR,Steinauer J,Yaksh TLdoi
10.1097/ALN.0b013e31823cf035subject
Has Abstractpub_date
2012-01-01 00:00:00pages
170-81issue
1eissn
0003-3022issn
1528-1175journal_volume
116pub_type
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