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Br J Pharmacol. 2019 May 2. doi: 10.1111/bph.14696. [Epub ahead of print]

Histamine, histamine receptors, and neuropathic pain relief.

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School of Pharmacy, Newcastle University, Newcastle upon Tyne, UK.
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
School of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK.
Department of Biosciences, Durham University, Durham, UK.


Histamine, acting via distinct histamine H1 , H2 , H3 , and H4 receptors, regulates various physiological and pathological processes, including pain. In the last two decades, there has been a particular increase in evidence to support the involvement of H3 receptor and H4 receptor in the modulation of neuropathic pain, which remains challenging in terms of management. However, recent data show contrasting effects on neuropathic pain due to multiple factors that determine the pharmacological responses of histamine receptors and their underlying signal transduction properties (e.g., localization on either the presynaptic or postsynaptic neuronal membranes). This review summarizes the most recent findings on the role of histamine and the effects mediated by the four histamine receptors in response to the various stimuli associated with and promoting neuropathic pain. We particularly focus on mechanisms underlying histamine-mediated analgesia, as we aim to clarify the analgesic potential of histamine receptor ligands in neuropathic pain.


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