Comparison of different tools for pain assessment following ovariohysterectomy in bitches

Introducction

Definition of pain in human is an unpleasant sensory and emotional experience associated with actual or potential tissue damage (Wright and Aydede, 2017) and the definition of animal pain is an aversive, sensory experience representing awareness by the animal of damage or threat to the integrity of its tissues; (note that there might not be any damage)  (Heuberger et al, 2016; Molony, 1997).

Postoperative pain is classified as acute and associated with actual or potential tissue damage (Duthie, 1998; Stessel et al., 2017; Yazbek and Fantoni, 2005;). Although accurate identification and assessment of the degree of pain being suffered by an animal can be a challenge (Landa, 2012; Sharkey, 2013), control of painful condition is becoming an increasingly important part of veterinary medicine (Jirkof, 2017; McMillan et al., 2008). Because of the lack of verbal communication, the level of postoperative pain in dogs is difficult to assess. Therefore, the assessment of pain in veterinary medicine relies on temperament, vocalization, posture, activity level, locomotion, reaction to palpation, and other behavioral changes and it should be considered that threshold and response to pain varies according to species, breed, healthy status and age (McMillan, 2016; Vedpathak et al., 2009). All those criteria are subjective and prone to numerous external factors. The objective indicators of pain are physiological and biochemical responses and pain threshold. The purpose of multimodal assessment of pain is to achieve objectiveness and credibility of results (Matičić et al., 2010). An important issue regarding pain management is familiarity with the personality of the animal subject to evaluation. In this instance the pet owner may be the best person to evaluate, for example, the level of anxiety or pain that the patient may be experiencing (Bufalari et al., 2007; Mathews, 2000). Pain assessment in animals is the mandatory step in the successful management of pain. For successful assessment, a number of scales have been used such as Simple Descriptive Scale (SDS), Visual Analogue Scale (VAS), and University of Melbourne Pain Scale (UMPS) (Bufalari et al., 2007; Hielm-Björkman et al 2011).

The SDS as the simplest of the three scales usually consists of four or five expressions used to describe various values of pain intensity, e.g. no pain, mild, moderate, or severe pain. Each expression is assigned a number, which becomes the pain score for that animal (Leonardi et al., 2006).

 VAS is a measurement that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot be directly measured. For example, the amount of pain that a patient feels ranges across a continuum from none to an extreme amount of pain (Elfving et al, 2016). VAS has been used by human patients to evaluate their own severity of pain, it includes the use of a line in which the left end of the line represents no pain and the right end of the line represents the most pain possible. Patients then indicate the intensity of the pain by placing a mark on the line (Elfving et al 2016; Lawrence et al., 1993). When a VAS is used for estimating pain in animals, the animals are observed, and the location at which  the mark is placed is determined by an observer (Hielm-Björkman et al., 2011).

The University of Melbourne Pain Scale (UMPS) is one of the multiparametric scales used to assess postoperative pain in dogs which also considers interaction between the animal and the evaluator. UMPS is a scale based on specific behavioral and physiological responses and includes multiple descriptors in six categories of parameters or behaviors related to pain (Matičić et al., 2010).

Various agents can be used for pain relief, including centrally acting analgesics and non-steroidal anti-inflammatory agents (Yazbek and Fantoni, 2005). Some researchers showed that preoperatively administration of carprofen could alleviate pain in dogs (Welsh et al., 1997) and the same results were obtained with morphine and buprenorphine by the others (Brodbelt et al., 1997; Snyder et al, 2016). The analgesic properties of tramadol result from mixed opioid and nonopioid mechanisms (Manne and. Gondi, 2017; Monteiro et al., 2009). The nonopioid mechanism was shown to inhibit the reuptake of noreepinephrine and serotonine (Beakley et al 2015; Duthie, 1998) and possibly displacement of stored 5 hydroxytryptamine from nerve endings in spinal and supraspinal pathways (Driessen and Reimann,1992; Raffa et al., 1992), therefore preventing impulses reaching the brain (Beakley et al 2015; Duthie, 1998). Tramadol has low affinity for µ receptors and an analgesic potency of one-tenth that of morphine (Monteiro et al., 2009), however, tramadol produced similar analgesia to morphine in the early postoperative period following ovariohysterectomy in dogs (Mastrocinque and Fantoni, 2003). In human beings it has been reported that the incidence of nausea and vomiting of tramadol was lower than that of other opioids (Duthie, 1998). Human field investigations showed tramadol in comparison with morphine produces less respiratory depression, does not release histamine and when used in therapeutic dosages does not have any effect on heart rate, ventricular function and blood pressure (Houmes et al., 1992). On the other hand, some side effects such as the decrease in prostacycline and prostaglandins synthesis which have been seen by non-steroidal anti-inflammatory drugs, do not occur with tramadol (Allegaert, 2016; Raffa et al., 1992).

The aim of this study was to compare different tools that would facilitate clinical evaluation of postoperative pain in dogs and to seek a simple and practical way to assess pain in this species.

Materials and Methods

This experimental study was carried out in ten adult mixed breed bitches weighing between 15 and 25 kg and aged between 1.5 and 3 years. Physical examination and complete blood count and biochemical serum analysis were performed in all dogs. Dogs were randomly divided into two equal treatment and control groups. Food and water was withheld from all dogs for 12 and two hours, respectively.

Ovariohysterectomy was performed under general anesthesia. Dogs were premedicated with intramuscular acepromazine 0.03mg/kg (Acepromazine 2%, Kela laboratoria NV., Belgium), administered 20 minutes before anaesthetic induction. Anesthesia was induced with Sodium thiopental (Biochemic GmbH, Vienna- Austria), 6-10 mg/kg intravenously. After endotracheal intubation, anesthesia was maintained using halothane (Pacegrove LTD., England)) at a concentration of 1 to 1.5% delivered in oxygen by using a closed circuit. Anesthetic was kept constant by the use of classical signs of anesthetic depth. All ovariohysterectomies were performed by a single trained surgeon. Duration of anesthesia and duration of surgery were recorded.

Treatment group received 3 mg/kg of tramadol (MS Pharma, USA) intramuscularly and control group received normal saline (equal volume with tramadol, i.m.) before the anesthetic induction. The injections of tramadol or normal saline were repeated four times a day with 6 hour intervals in 7 days. The animals were monitored at hour 2, 3 and 4 after each injection. Dogs were scored for signs of pain by two trained assessors who were blinded to the groups. The assessors were a general veterinary practitioner with minimum 5 years’ experience in the field of small animal practice. If a dog appeared uncomfortable at any time during the postoperative period, or if the total score of UMPS scale was higher than 8, tramadol was administered at 3mg/kg, i.m. as a rescue analgesic.

The variables measured were pain assessment with different methods including Simple Descriptive Scale (SDS) (Table 1), Visual Analogue Scale (VAS) (Table 2), and University Melbourne Pain Scale (UMPS) (Table 3). Statistical analysis of collected data was done using the SPSS 16 program. Parametric variables were analyzed using Student’s t-test or repeated measures ANOVA as appropriate. Non-parametric variables were analyzed by chi-square test (χ2 test). The minimum level of significance was defined as p<0.05

Table 1: Simple Descriptive Scale (SDS) for scoring of abdominal pain in dogs (according to Mastrocinque and Fantoni, 2003)

Table 2: Visual analogue scale, for assessment of abdominal pain in dogs.

Table 3: University Melbourne Pain Scale (UMPS) for scoring of abdominal pain in dogs (according to Firth and Haldane, 1999 )

* Includes turning head toward affected area; biting, licking, or scratching at the wound; snapping at the handler; or tense muscles and a protective (guarding) posture. ** Does not include alert barking. Minimum total score=0, maximum total score=27

Table 4 - Body weight, age, duration of anesthesia and duration of surgery in dogs undergoing ovariohysterectomy. (Mean ± SD) *

*No significant differences were seen between these criteria in two groups

Results

There were no significant differences among groups for body weight, age, duration of anesthesia and duration of surgery (p>0.05) (Table 4).

With regard to analgesia that was measured with VAS, SDS and UMPS methods, only UMPS  showed highly significant analgesia in treatment group (p<0.01) (Fig. 1) and VAS and SDS did not reveal any significant changes between groups (p>0.05) (Table 5 and 6). One dog in the control group was treated with supplemental tramadol.

In comparison with before surgery, heart rate decreased in treatment group significantly at day 1, 3, 4, 5, 6 and 7, and in control group significant increase of heart rate was seen on the first day after surgery (p<0.05) (Table 7).

Rectal temperature and respiratory rate did not show any significant changes in both groups.

Table 4 - Body weight, age, duration of anesthesia and duration of surgery in dogs undergoing ovariohysterectomy. (Mean ± SD) *

*No significant differences were seen between these criteria in two groups

Table 5: Visual Analogue Scale (VAS) in both groups after ovariohysterectomy (Mean ± SD) *

*No statistically significant changes were seen between groups (P>0.05)

Table 6: Simple Descriptive Scale (SDS) in both groups after ovariohysterectomy (Mean ± SD) *

*No statistically significant changes were seen be

tween groups (P>0.05)

Table 7: Heart rate
(beat/minute) in both groups after ovariohysterectomy (Mean ± SD) (Mean±SD)

*The changes were significant in compare with before surgery in each group (P<0.05).

Discussion

Pain is an individual experience and there is no objective method of measuring it today. In order to increase sensitivity and decrease bias while measuring the pain parameters, multiple objective and subjective pain assessment methods have been used (Matičić et al., 2010; Sharkey, 2013).

In the present study ovariohysterectomy was used as a model of surgical trauma for evaluation of three methods used for assessment of pain in dogs. Much of the animal pain research has focused on acute pain, and the most common model used for this purpose is ovariohysterectomy of dogs. Ovariohysterectomy is a relatively standardized source of soft tissue pain which makes it suitable for clinical studies of analgesia (Hansen, 2003; Tsai et al., 2013). It is generally accepted that this surgical procedure causes some degree of moderate pain (Caulkett et al., 2003; Fox et al., 1994; Mastrocinque and Fantoni, 2003) while in the present study two subjective pain scales (VAS and SDS) did not show any significant changes between control and treatment groups.

 Simple descriptive scales have  initially been used for humans since 1975, but the application of these methods in animals is a relatively complex task to perform. This scale is easy to apply but its sensibility is weak (Holton et al., 2001). SDS is a scale based on observation of the animal and not the nature of the procedure performed. The main disadvantages of the SDS are that it is not a sensitive scale for assessment of pain because it consists of only four or five categories and observer bias may play a key role in determining the pain scale. On the one hand, some researchers believe that SDS in not adaptable to animals since it is not precise and specific (Bufalari etal., 2007). On the other hand, VAS like SDS is a scoring system that is used extensively for people and is generally completed by the patient experiencing the pain. The scale avoids the use of imprecise descriptive terms and provides many points from which to choose.

In veterinary medicine, VAS is used for the evaluation of acute (Holton et al., 1998), postoperative pain in dogs (Firth and Haldane, 1999) and cats (Cambridge et al, 2000). To avoid possible mistakes, it is necessary that the observer be well trained to recognize animal behavior during pain status and to discriminate species differences. Key disadvantages of the VAS in veterinary medicine occur primarily because the scale relies on an observer to identify and interpret pain behaviors. Observer bias may play a key role in assessment of pain, leading to the possibly of overdiagnosing or underdiagnosing pain. The most obvious limitation of VAS scale is that it simply places a numerical value on a subjective judgment, and indeed  significant variability exists among observers with this device (Hansen, 2003; Holton et al., 1998).

There is no universal or self-sufficient pain assessment system. The comparison of clinical findings and behavioural parameters increase the objectivity of the results and help to explain their relationships, thus making the overall pain response clearer for the observer (Matičić et al., 2010). Some studies showed that UMPS is a reliable method of clinical pain assessment in dogs (Firth and Haldane, 1999; Matičić et al., 2010). The UMPS is regarded as more sensitive and more accurate than many descriptive and numerical rating scales (Firth and Haldane, 1999; Grant, 2006; Mich and Hellyer, 2008).The UMPS recognizes the importance of specific behavioural patterns, thereby eliminating the observers’ bias. The behavioural and physiological parameters are taken into account and divided into six categories: physiologic data, response to palpation, activity, mental status, posture, and vocalization. The application of multiple parameters results in better accuracy and sensibility. The limitations of the system are the incapability of detecting subtle behavioural changes, the exclusive use for postoperative patients and the requirement of broad knowledge of manifestations of pain in animals (Matičić et al., 2010; Mich and Hellyer, 2008).

Clinical parameters used for the assessment of acute pain are heart rate, respiratory rate, temperature, arterial pressure and mydriasis (Matičić et al., 2010). The first reaction to painful stimulus is the increase of these parameters, but it seems after stabilization of the circulatory system these criteria lose their significance (Mich and Hellyer, 2008). Clinical parameters by themselves are not specific enough to differentiate pain from anxiety or fear, but these conditions can influence the circulation. The analgesic agents, like opioids, can decrease the clinical response, even in the case of insufficient analgesia (Hansen, 2000).

In our study significant increase in  heart rate in control group was only seen on the first day after operation and surgical trauma and probably pain might be a logical reason for this change, although some researchers showed low correlation between clinical and behavioral parameters of pain in animals (Conzemius et al., 1997). Opioid-like effect of tramadol can explain the decrease inheart rate in most of the days after surgery in treatment group and this phenomenon may happen even in the case of insufficient analgesia (Hansen, 2000).

Comparison of the clinical and behavioral indices increases the objectivity of the results and helps to explain their relationships, thus making the overall pain response clearer for the assessors. Although our study did not demonstrate concordance of the dynamics of pain measured by the SDS, VAS and UMPS, indicate the greater reliability of UMPS method of pain assessment in dogs.

Acknowledgements

The authors would like to sincerely thank Shahid Chamran University of Ahvaz  for the use of their facilities and the financial support.