Monday, March 26, 2018

Research Review: NSAIDs reduce the effectiveness of electro-acupuncture on decreasing pain and inflammation

key words:  electro-acupuncture, ischemia reperfusion, pain gateway theory, COX-2-dependent mechanism, randomized controlled crossover trial, pilot study, celecoxib, guest post, research review, pain management, STRICT-A review, biomedicine review, biomedical pharmacology review


Bonuses (near end of post):
  • STRICT-A compliant review of article
  • Links to resources for reviewing the biochemical inflammation response, focus on the COX pathways, and the related drugs used to treat inflammation via these pathways, pharmacology review

Acronyms
COX-2 = cyclo-oxygenase 2.  A biochemical cell-signalling mechanism related to inflammation and pain.
IR = ischemia reperfusion
EA = electro-acupuncture
NSAID(s) = non-steroidal anti-inflammatory drug(s)

Reference
Lee S.M. et al. (2017). Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism:  A randomized controlled crossover trial.  Plos One12(6).  doi: 10.1371/journal.pone.0178838
link:  https://www.ncbi.nlm.nih.gov/pubmed/28591155

Introduction
The researchers are focusing on endothelial dysfunction as neutrophils and other inflammatory cytokines have been linked to ischemia reperfusion (IR).  By focusing on IR, the authors are studying the pain gateway theory albeit in a more cost-effective manner.  In the paper, the authors discuss pain control theory.

Study type:  randomized controlled crossover trial, pilot study

Category of research: Pilot study

Summary of the article
One can tell the researchers took time with the study as it follows the pain gate way theory. The first protocol demonstrates the benefits of EA by inhibiting COX-2 found in the spinal dorsal horn by decreasing inflammation and reducing neuropathic pain.  The 2nd protocol demonstrates how NSAIDs may inhibit EA full potential.

Reviewer's interpretation
The authors are interested in the reduction of tissue damage post periods of ischemia, i.e. lack of oxygen.
By definition, ischemia reperfusion may cause injury to the endothelial tissue after a time of no oxygen.  The researchers made medical assumptions in an effort to study EA in a cost effective and more independent review board (IRB) approved manner due to working with humans.
The inflammatory markers for pain are similar to the inflammatory markers in ischemic tissue.  The authors used the healthy volunteers to study blood vessel response after being constricted via a pressure cuff, no blood flow, no oxygen.  Reducing the pressure, the researchers used an ultrasound machine to see the difference of rebound in the vessel with EA vs. sham EA.
So, technically, with medical terminology and the pressure cuff, there is no blood flow nor oxygen to the artery.

The study is looking at how to slow or decrease the problem of tissue damage, particularly tissue damage due to lack of tissue oxygenation.  

The researchers hypothesize that the electro-acupuncture would be beneficial due to the pain gateway theory in COX-2 dependent mechanism.  As it is the first study on humans using this theory, this is a Pilot Study.

The study shows that electro-acupuncture is beneficial to decrease inflammation

It also suggests that NSAIDs and other pharmaceutical medication may inhibit the full benefits of electro-acupuncture. 
Therefore, acupuncture and the treatment will be more effective when the patient is not on medication.

Please give a warm welcome to 
our guest blog post author today, Liz D!
Hi, my name is Liz D.  BS, MSAOM, EAMP, LMP.  After 15 years in the healing arts, I am currently in the final stretches of earning my DAOM at Bastyr University along with participating in clinical rounds at Harborview Medical Center.

Bonus:  A STRICTA Review of this article
Apparently, I went a little overboard for the first blog and did a quick recap of the research via STRICTA (Standards for Reporting Interventions in Controlled Trials of Acupuncture) oops.  If you're still reading, enjoy...

The article is a pilot randomized crossover trial.  The hypothesis involves the response and mechanism of electro-acupuncture (EA) in ischemia-reperfusion (IR) induced endothelial dysfunction in humans compared to the effect and mechanism of COX 2-dependent medication.  The 2-part study involved twenty "healthy volunteers" in either EA or sham EA followed by 7 of twenty non-randomized/non-blinded volunteers taking a 15-day wash out from acupuncture then ingesting COX-2 inhibitor, celecoxib 200mg 2x/day for 5 days.  The original inclusion factors involved non-smoking and between the ages of twenty-five to forty years old.  The researchers excluded volunteers who had hypertension, diabetes, hepatic renal, thyroid, cerebrovascular disease, pregnancy, BMI greater than 25 kg/m and later excluded volunteers taking supplements or enrolled in another clinical trial.  The volunteers in the first protocol were blinded via computerized random allocation sequence with permutable block design.

Protocol 1 involved unilateral EA treatment at P5, P6, ST 36, ST37 (0.25mm x 40mm) low frequency ES-160, ITO at 1 cm depth at anterior forearm and 2 cm depth at anterior leg.  The practitioner rotated the filiform a few times before achieving "de qi" then connecting to ITO at 2 Hz continuous.  The non-EA points were located 10-20 mm lateral to P5, P6, St 36, St 37 but not above the median line at a depth of 0.5 cm and did  not achieve de qi.  The ES machine made similar sounds to ITO but did not stimulate frequency.

Ischemia-reperfusion (IR) and flow-mediated dilation (FMD) were used as measurement.  The volunteers rested 10 minutes in supine position prior to protocol.  IR and FMD were measured after receiving EA or sham EA.  In the sham EA as well as the active EA group, BA diameter and blood flow values were not different from baseline value before and after IR.  Instead, sham EA had a decrease in FMD after IR.  EA prevented the impairment in endothelium-dependent vasodilation induced by IR injury.  FMD was significantly shortened after IR, showing COX-2-inhibitor prevented EA induced endothelial protection against IR.  This is the first human study showing the response of EA on "endothelial pharmacological preconditioning" and further theorizes the mediation of COX-2-dependent mechanism.

PLOS ONE is a peer-reviewed non-profit 501c3 journal.  It has over 6000 academic experts on editorial board.
Limitations to the study involve small sample size, single center and the volunteers were considerably healthy.

Biomedicine Review Resources:  
Inflammation Process (COX pathways) and Pharmacology of NSAIDs




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