Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic–Pituitary–Adrenal Axis During Ethanol Withdrawal

Zhao, Zheng Lin; Kim, Sang Chan; Zhang, Jie; Liu, Hong Feng; Lee, Bong Hyo; Jang, Eun Young; Lee, Chul Won; Cho, Il Je; An, Won Gun; Yang, Chae Ha; Kim, Young Woo; Zhao, Rui; Wu, Yi

doi:10.1016/j.jams.2015.05.007

Cited by 6 publications

(5 citation statements)

References 17 publications

(23 reference statements)

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“…reported that the anti-nociceptive action of caffeine is mediated by norepinephrine signaling in the locus coeruleus and spinal cord 20 . In contrast, several studies reported that acupuncture attenuates norepinephrinergic transmission 28, 29 . Thus, acupuncture may counteract the anti-nociceptive action of caffeine, resulting in an apparent increase of mechanosensitivity.…”

Section: Discussionmentioning

confidence: 96%

Presence of caffeine reversibly interferes with efficacy of acupuncture-induced analgesia

Fujita

Feng

Takano

2017

Sci Rep

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Acupuncture is an alternative treatment for wide spectrum chronic pain. However, its validity remains controversial due to the disputed efficacy assessed in various clinical studies. Moreover, variability amongst individuals complicates the predictability of outcome, which impedes the integration of acupuncture into mainstream pain management programs. In light of our previous finding that the analgesic effect of acupuncture is mediated by adenosine A1 receptor activation at the acupuncture point, we here report that in acute and chronic animal pain models, oral intake of caffeine, a potent adenosine receptor antagonist, interferes with acupuncture analgesia, even at a low dose. Local administration of caffeine at the acupuncture point was sufficient to eliminate the analgesic effect, dismissing the systemic action of caffeine. Such interference was reversible, as caffeine withdrawal fully restored the efficacy of acupuncture by the next day, and long-term exposure to caffeine did not alter A1 receptor expression at the acupuncture point. Combined, these data indicate that a trace amount of caffeine can reversibly block the analgesic effects of acupuncture, and controlling caffeine consumption during acupuncture may improve pain management outcomes.Analgesia is one of the most widely accepted effects of acupuncture. However, acupuncture's efficacy beyond the placebo effect still remains controversial, primarily because of an incomplete understanding of its biological basis. The credibility is further diminished by the high variability of the efficacy, ranging from complete pain relief to no effect at all. Thus, acupuncture is often used as a last treatment option, even though pain reduction as a result of acupuncture has been demonstrated in many human and veterinary patients, without adverse side effects that are often present with medications.We previously showed that, in an animal model, the analgesic effect of acupuncture is mediated by a steep increase in extracellular adenosine levels at the acupuncture point and subsequent local activation of the adenosine A1 receptor 1 . The A1 receptors responsible for mediating analgesia are localized in the vicinity of the acupuncture point rather than at distant central nervous system. This is evident since local administration of the A1 receptor agonist, 2-Chloro-N6-cyclopentyladenosine (CCPA), at the acupuncture point also resulted in analgesia, while acupuncture applied to the contralateral leg to the site of pain failed to reduce pain 1 . Such a transient adenosine increase was also present with acupuncture in humans 2 .Adenosine receptor activation during acupuncture analgesia is potentially impacted by caffeine, which is a potent adenosine receptor antagonist. Caffeine is present in a wide variety of foods and drinks, and it is estimated that around 90% of the US population consumes caffeine daily 3 . Even though the average half-life of caffeine in plasma is 4-5 hours, a detectable amount of caffeine stays in the body for more than 12 hours after drinking a cu...

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Section: Discussionmentioning

confidence: 96%

Presence of caffeine reversibly interferes with efficacy of acupuncture-induced analgesia

Fujita

Feng

Takano

2017

Sci Rep

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“…Finally, acupuncture regulates the metabolism of catecholamines. Acupuncture decreases levels of norepinephrine and epinephrine in the plasma and renal tissues of spontaneously hypertensive rats 109 and levels of norepinephrine in the hypothalamus of alcoholic rats 117 . Thus, acupuncture may alleviate pain and reduce neuroinflammation, in part, by restoring deficiencies in catecholamine metabolism.…”

Section: Discussionmentioning

confidence: 96%

Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions

Kim

Zhang

O'Buckley

et al. 2018

The Journal of Pain

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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.

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“…The accumulated evidences demonstrate that the neurotransmitter systems, such as norepinephrine, glutamate, serotonin and dopamine, elicit effects on NTs . It is possible to facilitate the release of a certain transmitter in the CNS and subsequent activation of a related receptor and downstream signaling pathway by means of acupuncture or EA . Accordingly, the modulation of neurotransmitter system may be one candidate potential mechanism underlying the regulation of neural plasticity by acupuncture.…”

Section: Discussionmentioning

confidence: 99%

Applications of Acupuncture Therapy in Modulating Plasticity of Central Nervous System

Xiao

Wang

et al. 2018

Neuromodulation: Technology at the Neural Interface

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Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic–Pituitary–Adrenal Axis During Ethanol Withdrawal

Cited by 6 publications

References 17 publications

Presence of caffeine reversibly interferes with efficacy of acupuncture-induced analgesia

Presence of caffeine reversibly interferes with efficacy of acupuncture-induced analgesia

Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions

Applications of Acupuncture Therapy in Modulating Plasticity of Central Nervous System

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