Light-activated drugs for treating neuropathic pain

Light can be used to activate drugs in specific areas of the body using photopharmacology. This innovative approach involves modifying the chemical structure of a drug by adding a light-activated molecular switch, such as azobenzene. In this way, the drug can be made to activate only when exposed to a particular colour of light, and not in the dark.

Based on these principles, a research team led by the Institute for Bioengineering of Catalonia (IBEC) has developed photoswitchable derivatives of carbamazepine, an antiepileptic drug widely used in medicine, to combat some types of neuropathic pain, such as trigeminal neuralgia.

These compounds, which have an analgesic effect after being activated with light, are capable of inhibiting nerve signals locally and on demand. The derivatives synthesized by the researchers are activated at wavelengths that allow them to pass through tissue and bone.

The two synthesized compounds, carbazopine-1 and carbadiazocine, show photopharmacological activity, allowing reversible light control of the activity of hippocampal neurons and the locomotion of zebrafish larvae.

These in vivo experiments allow us to observe anxiety-related behaviours, which are reflected in sudden swimming movements. As Luisa Camerin, IBEC researcher and first author of the study, explains: “When we illuminate the larvae that have absorbed these compounds with a specific wavelength, the drug is activated and the larvae move faster. When we change the wavelength, their movement is reduced again, which demonstrates the reversible effect of the compound on the nervous system.”

Zebrafish larvae were used in the experiments. (Photo: IBEC)

Furthermore, carbadiazocine has also demonstrated analgesic properties: “We have observed, in rat models developed in the laboratory of Esther Berrocoso at the University of Cadiz, that carbadiazocine has an analgesic effect against neuropathic pain without signs of anesthesia, sedation or toxicity. These results demonstrate a simple and convincing treatment with noninvasive illumination,” explains Pau Gorostiza, ICREA research professor, principal investigator at IBEC and member of the Biomedical Research Network Center for Bioengineering, Biomaterials and Nanomedicine (CIBERBBN) in Spain.

Neuropathic pain is caused by injuries or diseases of the somatosensory system, such as lumbar radiculopathy (“sciatica”), diabetic neuropathy, and chronic post-surgical pain. Treatment of this type of pain often requires opioids, painkillers that are more potent than the usual nonsteroidal anti-inflammatory drugs such as acetaminophen and ibuprofen. However, their use is controversial due to their inconsistent efficacy, the need for high doses that can cause tolerance and addiction, and systemic side effects such as constipation, nausea, dizziness, and drowsiness.

In this context, light-based therapies are gaining importance in medicine due to their ability to target specific regions of the body, increasing the effectiveness of treatment and reducing the side effects of systemic drugs.

The team is already working on the next step planned for this project, which is to activate the drugs using infrared light that penetrates deeper into the tissues, and using portable infrared light sources such as lasers or light-emitting diodes (LEDs).

This study is part of the PHOTOTHERAPORT project, coordinated by the Institute for Bioengineering of Catalonia (IBEC).

The study is titled “Photoswitchable Carbamazepine Analogs for Non-Invasive Neuroinhibition In Vivo.” It has been published in the academic journal Angewandte Chemie. (Source: IBEC)