Angiotensin receptors and neuropathic pain

Mihály Balogh, Clarissa Aguilar, Nicholas T. Nguyen, Andrew J. Shepherd*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)


Growing evidence implicates the renin–angiotensin system (RAS) in multiple facets of neuropathic pain (NP). This narrative review
focuses primarily on the major bioactive RAS peptide, Angiotensin II (Ang II), and its receptors, namely type 1 (AT1R) and type 2
(AT2R). Both receptors are involved in the development of NP and represent potential therapeutic targets. We first discuss the
potential role of Ang II receptors in modulation of NP in the central nervous system. Ang II receptor expression is widespread in
circuits associated with the perception and modulation of pain, but more studies are required to fully characterize receptor
distribution, downstream signaling, and therapeutic potential of targeting the central nervous system RAS in NP. We then describe
the peripheral neuronal and nonneuronal distribution of the RAS, and its contribution to NP. Other RAS modulators (such as Ang (1-
7)) are briefly reviewed as well. AT1R antagonists are analgesic across different pain models, including NP. Several studies show
neuronal protection and outgrowth downstream of AT2R activation, which may lead to the use of AT2R agonists in NP. However,
blockade of AT2R results in analgesia. Furthermore, expression of the RAS in the immune system and a growing appreciation of
neuroimmune crosstalk in NP add another layer of complexity and therapeutic potential of targeting this pathway. A growing number
of human studies also hint at the analgesic potential of targeting Ang II signaling. Altogether, Ang II receptor signaling represents a
promising, far-reaching, and novel strategy to treat NP.
Original languageEnglish
Article numbere869
Number of pages13
Issue number1
Publication statusPublished - Jan-2021
Externally publishedYes

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