Katarzyna Popiołek - Barczyk
-
Pharmacological modulation of histamine H3 and H4 receptors - a new perspective in the treatment of neuropathic pain - 2020-06-25 - 2023-06-23
Neuropathic pain is a chronic pain condition, which can develop when the nerves of the somatosensory nervous system become injured in consequence of various diseases, including tumours, diabetes, multiple sclerosis, HIV infections, or after surgeries. It is estimated that this type of chronic pain affects 6.9-10% of the general population and its pathology is more frequent in women (8%) compared to men (5.7%). Epidemiological studies demonstrate a higher occurrence of pain-related disorders (including migraine, fibromyalgia, arthritis) in women, which is connected with a frequent use of analgesics. Moreover, neuropathic pain is relatively less responsive to opioids than other types of pain, which is possibly due to a disrupted opioid system partially caused by a profound glial cells activation and neuroinflammation. Chronicity of symptoms and not fully understood development mechanisms make neuropathic pain a burning problem for the worldwide healthcare and represent a significant, yet unmet medical need. The results of our recent studies suggest that pharmacological modulation of histamine receptors H3 (H3R) and H4 (H4R) is particularly interesting direction for research on novel therapeutic targets for the management of neuropathic pain.
In the frame of our project we are planning a series of studies designed to investigate the mechanism of H3R and H4R antagonists-induced analgesia during neuropathic pain. The project proposes an innovative and comprehensive series of experiments, including the use of novel H3R and H4R antagonists. Moreover,
keeping in mind that increasing the efficacy of drugs is an important strategy for improving the management of chronic pain, the research tasks proposed in this project focus on the problem of the loss of opioids effectiveness in neuropathy. Our preliminary data show that H3R and H4R antagonists potentiate morphine
analgesia. This important implication of opioid effectiveness raises great hopes for future pain therapy. Therefore, in the present project we are planning to combine clinically used drugs (such as buprenorphine, oxycodone) with H3R and H4R antagonists to improve opioids effectiveness and minimalize therapeutic doses. An important aspect of neuropathic pain is gender-related pain prevalence, which still remains an
unexplored issue. Therefore
