Systemic hypertonic saline enhances glymphatic spinal cord delivery of lumbar intrathecal morphine

The glymphatic system: Current understanding and modeling

“…The results suggest not only that hypertonicity could be used to enhance drug delivery, but also that solutes in the extracellular space are transported, at least in part, by advection, because diffusive transport would typically decrease after water moves from brain cells to ECS (Thomas, 2022). In rats, systemic hypertonic saline enhanced the delivery of morphine to the spinal cord after lumbar intrathecal administration, resulting in enhanced antinociception (Blomqvist et al, 2022).…”

SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline

“…That finding is supported by recent clinical studies demonstrating that lumbar CSF tracers attain peak cisternal and intracerebral availability within 4 to 9 hours of administration, depending on the infusion volume ( Eide et al., 2021 ; Ringstad et al., 2018 ; Verma et al., 2020 ), indicating that hyperosmotic enhancement of intrathecal drug delivery in the clinic may require that HTS administration is delayed relative to the intrathecal injection. Further support for the therapeutic benefits of HTS-enhanced drug delivery is provided by a recent preclinical study demonstrating an increased antinociceptive effect of intrathecally administered morphine, when administered in conjunction with systemic HTS ( Blomqvist et al., 2022 ). In addition to using lumbar intrathecal administration route, future studies to determine the translational benefits of HTS would also include testing the efficacy of HTS-enhanced delivery of intrathecal large-molecule therapeutics and in treatment of preclinical disease models.…”

Gene expression in the dorsal root ganglion and the cerebrospinal fluid metabolome in polyneuropathy and opioid tolerance in rats

“…We also collected CSF samples (ca 100 μl/sample) as previously described ( Nirogi et al, 2009 ), and done by our group ( Blomqvist et al, 2022 ). The procedure was carried out under 2% isoflurane anaesthesia.…”