Animal models of chronic pain. Are naturally occurring diseases a potential model for translational research?

Abstract

Despite the vast amount of molecular data obtained from classical pain studies, there is an ongoing translational pain model crisis reflected by the reduced amount of new effective and safe compounds developed to treat chronic pain in humans. Naturally occurring chronic pain in animals may offer some advantages over induced models of chronic pain, including a natural development of the condition that induces pain, the heterogenicity of the population that affects, and the chronologic age in which they develop, among others. The identification and study of naturally occurring painful diseases that resemble a particular chronic painful condition in humans has been proposed as a potential tool to investigate the molecular mechanisms and thus, accelerating drug development at the preclinical and clinical level. Currently, certain types of chronic pain in companion and large animals have gained attention as potential translational models of chronic pain. Examples of these include canine and feline osteoarthritis, neoplastic diseases as osteosarcoma and bovine and equine lameness. The present review describes the limitations of animal models of chronic pain and briefly enters in how naturally occurring pain models could represent a translational approach to chronic pain.

Glycinergic Modulation of Pain in Behavioral Animal Models

“…The translation gap between preclinical and clinical efficacy has called into question the reliability of animal models of human pain conditions. A review by Herzberg and Bustamante (2021) reported failure rates of 90–95% in the clinical phase of drug development, and in 2010, it was revealed that the likelihood of an analgesic drug progressing beyond Phase I clinical trials was 10.7% ( Hay et al, 2014 ; as cited in Herzberg and Bustamante, 2021 ). The poor translation from animal studies to humans in the clinic may be a culmination of limitations such as behavioral testing favoring the sensory over the emotional aspects of pain and insufficient diversity among study cohorts.…”

“…However, there are concerns regarding the ability of these models to reflect the emotional facets of pain ( King et al, 2009 ; Herzberg and Bustamante, 2021 ). To attain a more complete perspective of pain in animal studies, it has been suggested to analyze evoked pain outcomes, via mechanical or thermal stimulation, alongside non-evoked tests which better assess the quality of life ( Mogil, 2009 ; Burma et al, 2017 ; Herzberg and Bustamante, 2021 ). For example, conditioned place preference experiments can determine if an analgesic drug is perceived as rewarding, indicating an overall improvement in the experience of the rodent ( King et al, 2009 ).…”

“…Animal models of chronic pain are adept at producing quantifiable pain-related behaviors (e.g., limb withdrawal, spino-bulbo-spinal reflexes, vocalization, and licking of the hind paw) which have been crucial in understanding the pathophysiology of pain ( Herzberg and Bustamante, 2021 ). However, there are concerns regarding the ability of these models to reflect the emotional facets of pain ( King et al, 2009 ; Herzberg and Bustamante, 2021 ).…”

“…Animal models of chronic pain are adept at producing quantifiable pain-related behaviors (e.g., limb withdrawal, spino-bulbo-spinal reflexes, vocalization, and licking of the hind paw) which have been crucial in understanding the pathophysiology of pain ( Herzberg and Bustamante, 2021 ). However, there are concerns regarding the ability of these models to reflect the emotional facets of pain ( King et al, 2009 ; Herzberg and Bustamante, 2021 ). To attain a more complete perspective of pain in animal studies, it has been suggested to analyze evoked pain outcomes, via mechanical or thermal stimulation, alongside non-evoked tests which better assess the quality of life ( Mogil, 2009 ; Burma et al, 2017 ; Herzberg and Bustamante, 2021 ).…”

The One Medicine concept: its emergence from history as a systematic approach to re-integrate human and veterinary medicine

“…As well as impacting on humans, chronic pain also occurs naturally in livestock e.g. sheep, cattle and swine [ 115 ] and therefore could be a candidate for a One Medicine approach, whilst corneal ulcers in sea lions have seen novel treatments developed based on applications from human medicine [ 116 ].…”