Histamine, acting through all four types of histamine H1-H4 receptors, is arguably the most pleiotropic molecule in the human body. Since the cloning of H3R in 1999, there has been an increased interest within the pharmaceutical industry to discover and develop ligands to this receptor to target several diseases including neuropathic pain. However, while evidence supporting H3Rs expression in nociceptive pathways, including our earlier studies showing H3R on a population of A delta fibres that regulate pain sensitivity, and a role for H3R in the modulation of mechanical pathological pain is continuously increasing, many of the findings reporting the functional implication of H3R in chronic pain have been somewhat contradictory. This discrepancy led us to a hypothesis that this is due to both the central and peripheral nervous system access of the drugs tested thus far. Recent development of a selective and peripherally acting/centrally-sparing H3R ligands has provided an interesting tool for validation of peripheral H3R as a potential target for therapeutic intervention in chronic pain, particularly in peripheral neuropathies where pharmacological effectiveness would be desired, but not limited to, peripheral nervous system and pain-related peripheral sensitization.
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Investigating the role of the histamine system in chronic pain
