Challenges with Assessing and Treating Pain in Research Primates: A Focused Survey and Literature Review

Abstract

Research primates may undergo surgical procedures making effective pain management essential to ensure good animal welfare and unbiased scientific data. Adequate pain mitigation is dependent on whether veterinarians, technicians, researchers, and caregivers can recognize and assess pain, as well as the availability of efficacious therapeutics. A survey was conducted to evaluate primate veterinary approaches to pain assessment and alleviation, as well as expressed challenges for adequately managing primate pain. The survey (n = 93 respondents) collected information regarding institutional policies and procedures for pain recognition, methods used for pain relief, and perceived levels of confidence in primate pain assessment. Results indicated that 71% (n = 60) of respondents worked at institutions that were without formal experimental pain assessment policies. Pain assessment methods were consistent across respondents with the majority evaluating pain based on changes in general activity levels (100%, n = 86) and food consumption (97%, n = 84). Self-reported confidence in recognizing and managing pain ranged from slightly confident to highly confident, and there was a commonly expressed concern about the lack of objective pain assessment tools and science-based evidence regarding therapeutic recommendations of analgesics for research primates. These opinions correspond with significant gaps in the primate pain management literature, including limited specific pharmacokinetic data and efficacy testing for commonly used analgesics in research primate species as well as limited research on objective and specific measures of pain in research primates. These results demonstrate that there are inconsistencies in institutional policies and procedures surrounding pain management in research primates and a lack of objective pain assessment methods. Demonstrating the gaps and challenges in primate pain management can inform guideline development and suggest areas for future research.

Development and validation of a cynomolgus macaque grimace scale for acute pain assessment

“…It would also be interesting to evaluate the interspecies utility of the CMGS across other macaque and primate species. Despite the importance of managing and treating pain 4 , there is a lack of evidence of therapeutic analgesic efficacy in primates with dosages often extrapolated from other species 6 , 7 . Other analgesic regimens should be compared using the CMGS to ensure clinical relevance.…”

“…However, there are very few pharmacokinetic and efficacy studies demonstrating therapeutic analgesic blood drug levels in nonhuman primates, and none for which analgesic agents are combined, a technique used to provide greater analgesic coverage in other species 4 – 7 . Most analgesic recommendations for nonhuman primates are extrapolated from other species and it has been demonstrated that these extrapolations are not always accurate due to factors such as species-specific metabolism 7 . Further, analgesic protocols are often poorly reported, in part, due to the lack of pain assessment tools that would justify pain treatment 8 .…”

“…Further, analgesic protocols are often poorly reported, in part, due to the lack of pain assessment tools that would justify pain treatment 8 . Thus there are challenges in treating pain in nonhuman primates due to difficulties with interpretation of observations, a lack of validated pain assessment methods, unknown species-specific pharmacokinetic data, and no specific analgesia efficacy testing 7 . Cynomolgus macaques are widely worked with in research 9 , making development of a pain grimace score in this species highly impactful.…”

“…For example, during development of the feline grimace scale, grimace scores obtained in presumed painful cats were compared to pain scores obtained with the ‘Glasgow composite measure acute pain scale-feline’, a validated pain assessment instrument in cats 32 . Primates do not have a validated pain assessment tool and behavior is frequently used for pain assessment, for example, evaluating decreased activity or guarding of limbs in painful animals 7 , 26 , 39 , 40 . However, assessing behavior can be labor intensive, is challenging to conduct with a large group of animals in a research setting, and requires specific training and oversight to do well.…”

“…However, timepoints can be estimated for when breakthrough pain might occur, for example, just prior to scheduled readministration of analgesia when blood drug levels are waning. The timing for these assessments can be based on the pharmacokinetics of the analgesic agents being administered[see for example 7 , 26 , 40 . This approach was used in a recent study that attempted to correlate pain-associated behaviors (e.g., slumped posture, decreased activity) with facial expressions (e.g., orbital tightening) in rhesus macaques that had undergone painful procedures before subsequent doses of analgesics were administered 26 .…”