RESUMO
BACKGROUND: Spinal cord atrophy provides a clinically relevant metric for monitoring MS. However, the spinal cord is imaged far less frequently than brain due to artefacts and acquisition time, whereas MRI of the brain is routinely performed. OBJECTIVE: To validate spinal cord cross-sectional area measurements from routine 3DT1 whole-brain MRI versus those from dedicated cord MRI in healthy controls and people with MS. METHODS: We calculated cross-sectional area at C1 and C2/3 using T2*-weighted spinal cord images and 3DT1 brain images, for 28 healthy controls and 73 people with MS. Correlations for both groups were assessed between: (1) C1 and C2/3 using cord images; (2) C1 from brain and C1 from cord; and (3) C1 from brain and C2/3 from cord. RESULTS AND CONCLUSION: C1 and C2/3 from cord were strongly correlated in controls (r = 0.94, p<0.0001) and MS (r = 0.85, p<0.0001). There was strong agreement between C1 from brain and C2/3 from cord in controls (r = 0.84, p<0.0001) and MS (r = 0.81, p<0.0001). This supports the use of C1 cross-sectional area calculated from brain imaging as a surrogate for the traditional C2/3 cross-sectional area measure for spinal cord atrophy.
RESUMO
BACKGROUND: Neuraxial opioids are widely used for intraoperative and post-operative analgesia. The risk of severe adverse effects including respiratory depression accompanies this analgesia, prompting the need for effective non-opioid alternatives. Systemic 1-amino-1-cyclobutanecarboxylic acid showed promise in preliminary studies to produce antinociception without observable toxicity. However, the effects of 1-amino-1-cyclobutanecarboxylic acid after intrathecal administration are unknown. The aim of this study was to determine whether intrathecal administration of 1-amino-1-cyclobutanecarboxylic acid produces antinociceptive effects in murine models and to elucidate its site and receptor mechanism of action. METHODS: Female CD-1 mice were randomized to receive intrathecal, intraperitoneal and intraplantar injections of 1-amino-1-cyclobutanecarboxylic acid. Animals receiving intrathecal injections were anaesthetized and injected between L5 and L6. Animals then received an intraplantar injection of 10% hypertonic saline into the right hindpaw and were video-recorded for 30 min. Videos were analyzed by a blinded observer who determined the duration that animals exhibited nocifensive responses. RESULTS: Intrathecal or intraperitoneal administration of 1-amino-1-cyclobutanecarboxylic acid reduced the time that animals exhibited nocifensive behaviour, whereas intraplantar administration produced no effect. The effects of intrathecal 1-amino-1-cyclobutanecarboxylic acid were restricted in dermatomal distribution, reversible and produced little or no depression of respiratory rate. An NMDA antagonist blocked antinociception, while mu-opioid or GABAB antagonists did not prevent ACBC antinociception. CONCLUSIONS: Intrathecal 1-amino-1-cyclobutanecarboxylic acid in mice produces robust, brief antinociceptive effects with a dermatomal distribution corresponding to the lumbar site of administration. This amino acid merits further exploration as a non-opioid neuraxial analgesic with little or no respiratory side effects. SIGNIFICANCE: The novel, non-opioid analgesic, 1-amino-1-cyclobutanecarboxylic acid, produced robust, reversible and localized antinociception in murine models of pain. This study provides evidence supporting further investigation and development of 1-amino-1-cyclobutanecarboxylic acid as a non-opioid spinal analgesic.
