Acupuncture and pharmacopuncture are as effective as morphine or carprofen for postoperative analgesia in bitches undergoing ovariohysterectomy 1

PURPOSE: To investigate the analgesic effect of acupuncture (AP) or micro-dose pharmacopuncture (PA), using carprofen or morphine, in bitches undergoing ovariohysterectomy (OHE). METHODS: Thirty five dogs were randomly assigned to five groups after sedation with acepromazine IM: AP, 0.5 mg.kg-1 of morphine subcutaneously (SC), 4 mg.kg-1 of carprofen SC, and PA with 0.05 mg.kg-1 of morphine or 0.4 mg.kg-1 of carprofen. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed after OHE by a blind observer for 24h, by dynamic visual analogue scale (DIVAS), Glasgow (CMPS-SF), Melbourne (UMPS) and Colorado University pain scale (CSU). Animals reaching 33% of the UMPS score received rescue analgesia with morphine IM. Non parametric data were analysed by Kruskal-Wallis or Friedman tests where applicable, followed by Dunn ́s test. Parametric data were analysed by two way ANOVA, followed by Tukey test. RESULTS: There were no differences among groups in number of rescue analgesia. Except for the DIVAS score where animals treated with morphine had the lowest score compared with AP and carprofen, at 1h after surgery, there were no other differences among groups. CONCLUSION: Acupuncture or pharmacopuncture were equally effective as morphine or carprofen to control postoperative pain in bitches undergoing ovariohysterectomy.


Introduction
Non steroid anti-inflammatory drugs (NSAIDs) and opioids have been extensively used for postoperative analgesia in dogs [1][2][3] . Adverse effects of opioids may include vomiting, dosedependent respiratory depression, urinary retention, excitement/ dysphoria and histamine release 3 . NSAIDs should not be used in patients suffering hepatic, renal, gastrointestinal and coagulation dysfunctions 4 .
AP may be an alternative to avoid the adverse effects of opioids and NSAIDs in acute and chronic pain management. This technique has been successfully used in animals to treat neurological syndromes and musculoskeletal diseases which culminate in pain 5 and several studies and reviews have addressed the analgesic and antinociceptive effects of AP and AP related techniques in acute pain in man 6 and dogs [7][8][9][10][11] . Postoperative analgesia of AP is comparable or even better than opioids or antiinflammatory drugs [8][9][10][11] , showing that AP has a clinical promising effect to treat postoperative pain in dogs.
Considering that AP produces antinociception and analgesia and that in some cases NSAIDs and opioids may produce adverse effects or may be contraindicated, the replacement of analgesic drugs in pre-anaesthetic medication prior to painful procedures is a potential and attractive use of AP. This would eliminate the adverse effects of conventional analgesics and reduce treatment costs. Other beneficial effects of AP beyond analgesia, which would be relevant in the perioperative period, are reduction of postoperative nausea, vomiting and sympathoadrenal responses in man 6 . Such features make AP ideal for a great range of patients, particularly those likely to develop adverse drug reactions or when adverse effects of drugs might be risky.
Although dry needle AP or electroacupunture (EA) appears to be as effective as NSAIDs and opioid analgesics for postoperative analgesia in bitches undergoing OHE 9,11 , maintenance of needles prior to anaesthesia might be cumbersome, particularly in agitated animals. In order to overcome this disadvantage, other techniques might be used for stimulation of acupoints. The most usually used techniques for stimulation of acupoints are application of heat (moxibustion) and low power laser AP, however both are time consuming and the last one requires specific equipment. A possible alternative would be the injection of substances or micro-clinical doses of drugs into acupoints, which is known as pharmacopuncture (PA). This method combines the traditional acupoint stimulation with the local delivery of a pharmacological agent and it is supposed to potentiate and prolong the drug effect 12 . Pharmacopuncture has been successfully used to sedate horses 13 and dogs 14 .
The hypothesis of this study was that AP or micro-dose PA would be as effective as the conventional doses of NSAID or morphine to treat postoperative pain in dogs. In order to test this hypothesis this study investigated the analgesic effect of the preventive administration of AP or micro-dose PA, using carprofen or morphine, in bitches undergoing OHE. This was assessed by comparing these treatments against two positive control groups (conventional dose of carprofen or morphine).

Methods
This study was conducted under the owners´ consent and after the Institutional Animal Research Ethical Committee approval. The study was prospective, randomized, and blind for pain assessment.
Thirty-five healthy bitches from several breeds were used. They aged 24±7 months and weighed 10.1±1.7 kg. One day before surgery all animals were evaluated and maintained in individual kennels. Selection criteria included docile, unpregnant and healthy bitches based on normal clinical and laboratorial assessment (haematocrit, total protein, alanine aminotransferase, creatinine and alkaline phosphatase). Animals were fasted for 12 h and water was removed for two hours prior to surgery. Animals reaching 33% of the UMPS score (nine points) received rescue analgesia with 0.5 mg/kg -1 of morphine IM.
In these cases animals continued to be assessed and were not excluded from the statistical analysis. Seven days after surgery all bitches were clinically assessed, weighed and surgical suture was removed.

Results
There were no statistical differences between groups for age, body weight and propofol induction dose. Surgery and anaesthesia duration were 9±3 and 18±6 minutes (mean and standard deviation) respectively in all groups. Heart rate was greater in AC compared to the other groups at some time points, but values were within the normal range for the species. There were no other differences in the cardiorespiratory variables, including end tidal isoflurane concentration, during anaesthesia among groups.
Rescue analgesia was performed in 12 out of 35 bitches (34%) ( Table 1). There were no differences among groups in number of animals receiving rescue analgesia or number of times rescue analgesia was performed.

Discussion
The study was designed to standardize the control However it is generally accepted that preventive rather than A group of animals submitted to false AP points has also not been included because it has been reported that the analgesic effect of false AP is either absent or of low intensity when compared to the use of real points 7 .
The UMPS was used to determine the use of rescue analgesia, based on the fact that the evaluator was more familiarized in using the scale, as this was the scale adopted in the Veterinary Hospital routine and therefore accuracy would be improved.
Another possible limitation of the study was that sedation may increase the pain scores in dogs and might contribute to the use of rescue analgesia. This was probably not the case in this study, as although most of the rescue analgesia was performed at 1 h after the end of anaesthesia, the UMPS has been previously validated and specially developed to be used postoperatively 17 . According to that the possible effect of sedation in increasing the pain score is less pronounced in the UMPS, when compared to CMPS, and by this time dogs were responsive to stimulation due to the short period of anaesthesia and surgery.
Considering that there is no information regarding the intervention point to use rescue analgesia based on the UMPS, it was decided to use 30% from the total score because this is considered the transition between light and moderate pain. This is also close to intervention score reported for the CMPS, which is 25% from the total score, i.e. 6 16 .
Probably the main limitation of this study was the relatively small sample size in each group. It was difficult to increase the sample size as this was a clinical study and several experimental groups were studied. The number of rescue analgesia was either two or three in all groups, showing that the analgesic effect of all protocols was similar.
Dogs receiving rescue analgesia were not removed from the data, to minimize type 2 error and to investigate duration and efficacy of rescue analgesia in treating pain. Other approach like continuing to use the same value of the pain score measured at the time point rescue analgesia was firstly administered would increase type 1 error, as well as data would not be genuine.

A strong motivation for withholding systemic analgesics
in animals is the concern for their potential toxicity or adverse Further clinical studies using PA and dry AP, as a promising alternative to pharmacological pain treatments, are encouraged, especially under conditions where the use of NSAIDs and/or opioids are contra-indicated.

Conclusions
Pharmacopuncture was as effective as acupuncture, and both were equally effective as either morphine or carprofen to control postoperative pain in bitches undergoing ovariohysterectomy. The clinical relevance is that PA might produce less adverse effects when compared to the use of the conventional doses of drugs.
The advantage of PA when compared to dry needle AP is that the injections may be performed quickly without maintaining the needles into acupoints before surgery.