A collaborative research effort between the Indian Institute of Science (IISc) in Bengaluru and TCG-CREST in Kolkata has led to the identification of a specific “brain circuit” linked to a side effect of chemotherapy known as “cold allodynia.” This significant finding was documented in the peer-reviewed journal Cell Reports, in a study entitled “Parabrachial inputs to the parafascicular thalamus drive sensory and affective-motivational responses to cold-allodynia in mice.”
Cold allodynia is a condition characterized by pain or discomfort triggered by cold temperatures that would typically be considered innocuous. It is classified as one of the symptoms of “chemotherapy-induced peripheral neuropathy,” which encompasses various neural side effects from chemotherapy, including heightened sensitivity to temperature, sensations akin to pins and needles, and generalized pain.
This particular condition is notably associated with oxaliplatin, a widely prescribed chemotherapy agent that contains platinum.
How did the researchers pinpoint and confirm the cause of cold allodynia?
Professor Arnab Barik from IISc, who co-authored the study, explained to The Indian Express that cold allodynia presents a unique challenge; it involves sensitivity to cold without a corresponding sensitivity to heat. While predominantly a result of platinum-based chemotherapy drugs, it can also stem from viral infections, injuries, or diabetes. Furthermore, although nerve damage may heal over time, the underlying cause can linger, potentially leading to chronic pain.
The research team conducted experiments using mice to investigate the origins of cold allodynia. “Our findings indicate that there is a specific ‘circuitry’ that undergoes alteration following chemotherapy exposure. Even after stopping the treatment and allowing for recovery, the pain persists, signifying changes in the brain that do not readily revert to baseline conditions,” Barik remarked.
The researchers focused on the neural pathways in the affected regions, determining how they connect to the brain. They discovered that the link between the lateral parabrachial nucleus and the parafascicular region of the thalamus undergoes significant modifications post-chemotherapy.
The lateral parabrachial nucleus comprises nerve cells situated in the upper brainstem responsible for processing signals related to pain, taste, respiration, and fluid balance. In contrast, the parafascicular region of the thalamus contains vital nerve cells that play essential roles in motor control and pain management.
Are these findings relevant to humans?
It is important to note that the invasive nature of the experiments conducted on laboratory mice prevents direct application to human subjects. Barik stated, “In the long term, we aim to explore pharmacological solutions to address this issue, followed by testing those solutions in mice. This approach could facilitate easier translation to human applications.”
“We are also investigating whether this discovery is limited to chemotherapy-induced pain or if it can be applied to other types, such as pain resulting from injuries. We are in the process of testing this hypothesis, with plans to work on reversing these effects over the next five years,” he added.
