Acupuncure vs Opioids for Post-Surgical Pain in Dogs: Who Wins?

My attention was recently drawn to a veterinary acupuncture study which appears, superficially, to show acupuncture to be equivalent to opioid analgesia for post-operative pain in dogs. Unfortunately, especially for the research subjects, the design of the study was deeply flawed, and the conclusions the data support are far weaker.

D. Groppetti, A. M. Pecile, P. Sacerdote, V. Bronzo and G. Ravasio. Effectiveness of electroacupuncture analgesia compared with opioid administration in a dog model: a pilot study. British Journal of Anaesthesia 107 (4): 612–18 (2011).

What They Did
The investigators randomly assigned six healthy dogs to each of two groups. One group was sedated with the anesthetic propofol while needles were inserted into purported acupuncture points as determined by Traditional Chinese Medicine (TCM) principles. (Which is a bit misleading since traditional acupuncture was applied only to humans and the translation of the principles to dogs is a modern invention of the West). After 40 min of intermittent stimulation of these needles with electrical current, the animals were fully anesthetized and surgically neutered.

The other group was also sedated with propofol for the same period of time and also received the narcotic pain medication butorphanol at a dose of 0.2mg/kg 15 minutes before surgery.

The surgery was done routinely (though the average length of time in surgery was about 35min for both groups, which is about twice as long as the procedure typically takes an experienced surgeon. Such studies often involve surgery by veterinary students, but it is not clear from the paper who performed the operations in these subjects). The dogs were monitored and assessed up to 24 hours after surgery for signs of pain according to a subjective pain scale by observers blinded to the treatment category. Heart rate, respiratory rate, and amount of anesthetic gas needed to keep patients asleep during the surgery were measured and compared between groups. Measurements of a chemical in the blood called beta endorphin were also taken from the beginning of the procedure until 24 hours after surgery.

What They Found
There was no difference in the objective measurements of heart rate and respiratory rate during the surgery between the two groups. There was a difference in the more subjective measurement of amount of anesthetic gas needed to keep the patient at a proper plane of anesthesia, but this difference was significant at only 1 of 5 points measured.

The beta endorphin levels measured were highly variable, and differed significantly between the two groups at only 2 of 10 points measured, the end of surgery and 3 hours after surgery.

Subjective pain scores were higher for the control group than for the acupuncture group at all points measured, and this difference was significant at 12 of 14 points measured, continuously from 30min after surgery until 10 hours after surgery.

None of the dogs in the acupuncture group required additional pain medication as determined by pain score, but 4 of 6 dogs in the control group did.

No apparent side-effects were seen in the opioid group, but interestingly 4 of 6 dogs in the acupuncture group vomited after surgery.

Major Problems
There are serious problems with this study, and these undermine the conclusions of the authors that the study, “ demonstrated the ability of electroacupuncture to decrease anaesthetic and analgesic requirements in dogs during and after surgical neutering.”

1. Was the intervention studied actually acupuncture?
Obviously, electrical stimulation of needles in the skin is not a traditional Chinese therapy dating back thousands of years. Apart from the selection of locations for the needles, it bears less resemblance to TCM than to TENS, Transcutaneous Electrical Nerve Stimulation. This is a conventional therapy dating from about the 1970s that has reasonably good evidence of benefit for post-surgical pain, and which appears to work, at least partly, through general stimulation of opioid pain receptors via beta endorphin.

One could argue that despite the use of electrical stimulation, this intervention counts as acupuncture because traditional TCM principles dictated where the electrodes were placed. However, extensive evidence shows that sham acupuncture, involving placing needles in random locations or even not piercing the skin at all, is just as effective for pain as using traditional TCM acupuncture points. The authors of this study even stipulate this when explaining why no sham acupuncture control was included:

In clinical trials, sham acupuncture is considered necessary to demonstrate how a treatment is effective. However, it was argued that every penetration of a needle through the skin, be it at an acupuncture point or not, produces physiological effects, partly due to activation of a pain-suppressing system in the spinal cord (diffuse noxious inhibitory controls).

So if TENS achieves pain control through non-specific activation of opioid receptors via beta endorphin by electrical stimulation of the skin regardless of the location, and if the intervention in this study consisted of achieving pain control through non-specific activation of opioid receptors via beta endorphin by electrical stimulation of the skin, and the effect did not depend on the location of needle placement, in what sense is this “acupuncture” at all rather than TENS? How does it validate the principles or practices of TCM?

2. Butorphanol Sucks!
The choice of comparator was wholly inappropriate in this study. Butorphanol is widely recognized as a weak analgesic inadequate to control surgical pain. Numerous studies have shown it to be weak and to have a duration of action of 20-45minutes (1-3). In one study, butorphanol was statistically no better than placebo as an analgesic.

In this study, a low dose of the butorphanol was given 15 minutes before surgery. This would likely have provided limited pain control, and would have worn off by the end of the 35-minute procedure. So the control dogs had weak analgesia during the procedure and essentially none afterwards. Apart from the fact that this choice of comparison can only serve to make the test intervention look far better than it would compared to effective, standard-of-care pain control, it seems a questionable ethical choice given the clear evidence that butorphanol is not an adequate analgesic for this sort of procedure. Fortunately, at least the dogs were given rescue analgesia with more effective drugs when the pain scale seemed to indicate it was necessary.

3. Statistics
Though it is not clear from the paper, and is a less significant problem, the authors made multiple statistical comparisons, and there is no indication of whether or not they adjusted the level of statistical significance to account for this. This is perhaps the most common statistical error in the veterinary literature. Given the small numbers of subjects in the two groups, such an error could easily create the impression of difference greater than chance where non actually exist.

What Does it Really Mean?
This paper confirms the conclusion supported by much prior research: sticking needles into the skin and running electrical current through them results in a non-specific response that elevates beta endorphin levels and can suppress pain. The same phenomenon occurs with any trauma, so one could conceivably suppress post-surgical pain by banging on the patient’s toe with a hammer. While the effects of TENS has real potential value for pain control, it has nothing to do with the traditional theoretical constructs of TCM or acupuncture, and it is misleading to refer to it as “electroacupuncture” at all.

During the time the butorphanol would be expected to be active (while the dogs were anesthetized and undergoing surgery), there were no differences in objective measures that one would expect to reflect pain, such as heart rate and respiratory rate. So the electrical simulation appears to have been as effective as the lousy opioid analgesic while the dogs were anesthetized. Similarly, there were few significant differences in beta endorphin levels between the groups (or possibly none, depending on the appropriateness of the statistical methods), which suggests that the “trauma” of the needle insertion and stimulation had only a modest non-specific effect on the opioid receptor system. Since the butorphanol likely had worn off by the end of the surgery, this small effect was clearly better than complete lack of analgesic therapy the control dogs received. But this is hardly relevant to a patient population treated properly with effective, multimodal analgesia. And given that most of the dogs in the treatment group experienced post-operative vomiting, likely due to the stimulation of the opioid receptor system, it cannot even be argued that this approach lacks significant side effects.

If the conclusions of this paper had been limited to those justified by the data, the study would be a useful bit of data to consider in investigating the role of TENS in post-operative pain control. Unfortunately, the title, abstract, and discussion sections all create the unjustified impression that somehow TCM and traditional acupuncture are as effective as opioid analgesics in controlling post-operative pain, or perhaps even better. This will only perpetuate the myths and misunderstanding surrounding acupuncture and encourage the use of traditional practices that have not, in fact, been shown to be appropriate for this purpose.

References
1. K A Grimm; W J Tranquilli; J C Thurmon; G J Benson.Duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs Am J Vet Res. January 2000;61(1):42-7.

2. K A Mathews; G Pettifer; R Foster; W McDonell. Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. Am J Vet Res. June 2001;62(6):882-8.

3. D C Sawyer1; R H Rech; R A Durham; T Adams; M A Richter; E L Striler. Dose response to butorphanol administered subcutaneously to increase visceral nociceptive threshold in dogs. Am J Vet Res. November 1991;52(11):1826-30.

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