Highlights
- •Sustained inhibition of catechol-O-methyltransferase led to persistent pain and neuroinflammation in mice.
- •ST36, but not sham, acupuncture alleviated pain.
- •ST36 acupuncture reduced spinal phosphorylated p38 expression and astrocyte activation.
- •The magnitude of the analgesic response was greater in rapid-healing MRL/MpJ mice.
Abstract
Patients with chronic overlapping pain conditions have decreased levels of catechol-O-methyltransferase
(COMT), an enzyme that metabolizes catecholamines. Consistent with clinical syndromes,
we previously demonstrated that COMT inhibition in rodents produces persistent pain
and heightened immune responses. Here, we sought to determine the efficacy of manual
acupuncture in resolving persistent pain and neuroinflammation in the classic inbred
C57BL/6 strain and the rapid-wound healing MRL/MpJ strain. Mice received subcutaneous
osmotic minipumps to deliver the COMT inhibitor OR486 or vehicle for 13 days. On day
7 after pump implantation, acupuncture was performed at the Zusanli (ST36) point or
a non-acupoint for 6 consecutive days. Behavioral responses to mechanical stimuli
were measured throughout the experiment. Immunohistochemical analysis of spinal phosphorylated
p38 mitogen-activated protein kinase, a marker of inflammation, and glial fibrillary
acidic protein, a marker of astrogliosis, was performed on day 13. Results demonstrated
that ST36, but not sham, acupuncture resolved mechanical hypersensitivity and reduced
OR486-dependent increases in phosphorylated p38 and glial fibrillary acidic protein
in both strains. The magnitude of the analgesic response was greater in MRL/MpJ mice.
These findings indicate acupuncture as an effective treatment for persistent pain
linked to abnormalities in catecholamine signaling and, furthermore, that analgesic
efficacy may be influenced by genetic differences.
Perspective
Chronic overlapping pain conditions remain ineffectively managed by conventional pharmacotherapies.
Here, we demonstrate that acupuncture alleviates persistent pain and neuroinflammation
linked to heightened catecholaminergic tone. Mice with superior healing capacity exhibit
greater analgesic efficacy. Findings indicate acupuncture as an effective treatment
for chronic overlapping pain conditions and provide insight into treatment response
variability.
Keywords
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Article info
Publication history
Published online: July 04, 2018
Accepted:
May 28,
2018
Received in revised form:
May 24,
2018
Received:
December 4,
2017
Footnotes
This work was funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke grants R01 NS072205 and P01 NS045685 and National Institutes of Health/National Institute of Dental and Craniofacial Research grant R56 DE025296 (A.G.N.), and National Research Foundation of Korea (the Korean Government [MSIP] grant 2014R1A5A2009936 (S.K). The funding sources had no influence on the experimental design, data analysis, or in the preparation of the manuscript.
J.J.P. has shared ownership of Meridius Medical Ltd, DongBang AcuPrime Ltd, and Meridius Medical LLC.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
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© 2018 by the American Pain Society
