Blood Pressure Drugs (ACE Inhibitors) May Cause Pain by Increasing Substance P
ACE inhibitors captopril and enalapril increased substance P levels in spinal cord and nerve tissue, inducing mechanical pain sensitivity (allodynia) in mice through NK-1 receptor signaling.
Quick Facts
What This Study Found
ACE inhibitors increase substance P levels in spinal cord and DRG, causing mechanical allodynia through NK-1R signaling. ACE normally degrades substance P, revealing a previously underappreciated pain-related side effect mechanism.
Key Numbers
10-day treatment; increased SP in DRG + spinal dorsal horn; allodynia reversed by L-733,060; intraplantar SP for 3 days caused allodynia; exogenous ACE blocked SP effect
How They Did This
Mouse model with 10-day captopril or enalapril treatment (IP or intrathecal). Paw withdrawal frequency to mechanical stimuli. Substance P immunohistochemistry in lumbar DRG and spinal dorsal horn. NK-1R antagonist (L-733,060) rescue. Exogenous ACE and SP injection experiments.
Why This Research Matters
ACE inhibitors are among the most prescribed drugs worldwide. Understanding that they can cause pain sensitivity through substance P accumulation may explain unexplained pain complaints in patients taking these medications.
The Bigger Picture
This study reveals an unexpected connection between blood pressure regulation and pain processing through the shared substrate substance P. ACE degrades substance P along with angiotensin I, meaning that ACE inhibitor therapy may inadvertently affect pain pathways — a finding with broad clinical implications.
What This Study Doesn't Tell Us
Mouse study — may not directly translate to human pain experiences. 10-day treatment may not reflect chronic clinical use. Only mechanical allodynia tested, not other pain types.
Questions This Raises
- ?Do ACE inhibitor users experience more pain sensitivity than people on other blood pressure medications?
- ?Could NK-1R antagonists help manage ACE inhibitor-related pain?
- ?Is this mechanism relevant to the cough side effect of ACE inhibitors?
Trust & Context
- Key Stat:
- ACE normally degrades substance P Blocking ACE with blood pressure drugs allows pain-signaling substance P to accumulate in spinal cord tissue
- Evidence Grade:
- Well-designed preclinical study with multiple routes of administration and pharmacological confirmation. Pre-clinical evidence requiring human validation.
- Study Age:
- Published in 2021, revealing a novel pain-related side effect mechanism for one of the most commonly prescribed drug classes.
- Original Title:
- Inhibition of angiotensin converting enzyme induces mechanical allodynia through increasing substance P expression in mice.
- Published In:
- Neurochemistry international, 146, 105020 (2021)
- Authors:
- Choi, Jae-Gyun, Choi, Sheu-Ran, Kang, Dong-Wook, Kim, Jaehyuk, Park, Jin Bong, Kim, Hyun-Woo
- Database ID:
- RPEP-05320
Evidence Hierarchy
Frequently Asked Questions
Can blood pressure medication cause pain?
This mouse study suggests yes — ACE inhibitors like captopril and enalapril increased levels of substance P (a pain-signaling molecule) in the spinal cord, causing heightened sensitivity to touch. ACE normally breaks down substance P, so blocking ACE lets this pain molecule accumulate.
Should I stop taking my ACE inhibitor if I have pain?
Don't stop medications without consulting your doctor. This is a mouse study and may not directly apply to humans. However, if you've developed unexplained pain since starting an ACE inhibitor, discussing this research with your doctor could be worthwhile — alternative blood pressure medications exist.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-05320APA
Choi, Jae-Gyun; Choi, Sheu-Ran; Kang, Dong-Wook; Kim, Jaehyuk; Park, Jin Bong; Kim, Hyun-Woo. (2021). Inhibition of angiotensin converting enzyme induces mechanical allodynia through increasing substance P expression in mice.. Neurochemistry international, 146, 105020. https://doi.org/10.1016/j.neuint.2021.105020
MLA
Choi, Jae-Gyun, et al. "Inhibition of angiotensin converting enzyme induces mechanical allodynia through increasing substance P expression in mice.." Neurochemistry international, 2021. https://doi.org/10.1016/j.neuint.2021.105020
RethinkPeptides
RethinkPeptides Research Database. "Inhibition of angiotensin converting enzyme induces mechanic..." RPEP-05320. Retrieved from https://rethinkpeptides.com/research/choi-2021-inhibition-of-angiotensin-converting
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.