Millions of people live with chronic pain, which makes improving treatment a major challenge for health professionals. At the moment, traditional painkillers such as opiates and local anaesthetics come with certain side-effects, including sedation and damage to the heart muscle. Furthermore, when treatment of a persistently painful area involves repeated injections, this has the added consequences of possible discomfort for the patient, increased risk of infection and potentially high costs.
Prompted by recent advances in nanotechnology, a team of researchers led by Dmitri Rusakov of University College London set out to discover whether an alternative pain relief system could be found that would deliver medicine to a target site and release it over a prolonged period of time. Their findings were published in the repository ‘Europe PMC’
With partial support from two EU grants for the projects NETSIGNAL and NEUROCLOUD, the scientists exploited layer-by-layer technology
to insert a nerve-blocking drug in tiny, multilayer capsules invisible to the naked eye.
Multilayer microcapsules and the nerve-blocking power of QX-314
Tests on animals have shown that the drug called sodium-channel blocker QX-314 provides stronger and longer-lasting pain relief than standard painkillers. It enters the nerve cells through two proteins, TRPV1 and TRPA1, which are found in heat- and pain-signalling neurons. To determine its effectiveness as a nerve block for persistent inflammatory pain, the team encapsulated QX-314 in biodegradable microcapsules.
The microcapsules were first injected into individual nerve cells in vitro. Just 4-10 picogrammes of the nerve-blocking drug were found to make the neurons progressively less responsive to pain.
Next, the researchers used tissue taken from the hind paws of rats to test how the encapsulated drug behaved when it was injected in an affected tissue area. Adjustments were then made to microcapsule properties so that the medication would be released slowly and over a long period of time.
In the in vivo experiments that followed, 50-100 microlitres of complete Freund’s adjuvant – an emulsion that causes inflammation and sensitivity to heat and pain – were injected into one hind paw of each rat. Once the rodents began showing signs of pain and inflammation, the team injected the QX-314-containing microcapsules into the affected area. Results showed that a single local injection provided strong pain relief that lasted over a week! Additionally, the microcapsules began to biodegrade five weeks after being injected into the body.
The rats’ movement and anxiety levels were also monitored during the experiments. Observations showed that when they were injected with the inflammatory substance, the animals moved more slowly and hid in the corners of the arena they were placed in. However, within two to four days after treatment with encapsulated QX-314, they demonstrated improved speed and less anxious behaviour, spending more time in the centre of the arena.
While nano-engineered microcapsules are a promising development in pain relief, further enhancements are needed to ensure long-lasting and efficient results. At the next stage, current achievements in the NETSIGNAL (Signal Formation in Synaptic Circuits with Astroglia) and NEUROCLOUD (A neural network builder with remotely controlled parallel computing) projects will be used to develop injection methods that provide more precise, remote-controlled drug delivery to the target site. Future goals also include the development of microcapsules with properties that can help to recognise target tissues or cells, for more focused pain relief.
For more information, please see: NETSIGNALNEUROCLOUD