A MULTIDIMENSIONAL PRECLINICAL INVESTIGATION OF FIBROMYALGIA MODELS: SUBCHRONIC SWIM AND BIOGENIC AMINE DEPLETION

Abstract

Pain is a multidimensional phenomenon, comprised of affective-motivational, cognitive-evaluative, and sensory-discriminative domains. In the presence of pain with no single determinable etiology, such as fibromyalgia, understanding the affective and cognitive dimensions of the disorder is crucial for adequate diagnosis and pain management. However, there is little empirical support for many of the primary animal models of fibromyalgia in replicating this disorder across all the dimensions of pain. Therefore, the current studies sought to evaluate two primary preclinical models of fibromyalgia – the reserpine and subchronic swim stress models – across all three pain dimensions and determine their predictive validity with an FDA-approved fibromyalgia pharmacologic, duloxetine (Cymbalta®). Further, these studies sought to combine these two preclinical models of fibromyalgia pain to determine if their compounded effect better replicates reported clinical manifestations and management profiles across the affective, cognitive, and sensory domains. Overall, the reserpine model was effective in producing mechanical hyperalgesia, and potentially time-dependent thermal hyperalgesia, but ineffective in replicating anxiety- and depression-like behavior. The subchronic swim stress model was effective in producing mechanical hyperalgesia, and time-dependent thermal sensitivity, as well as trending effects of depression-like behavior, but no changes in anxiety-like behavior. The combination of these models produced mechanical sensitivity, and potentially time-dependent thermal sensitivity, alongside anxiety-like behaviors and trending depression-like behaviors. However, all models failed to produce any changes in cognitive function. The administration of duloxetine selectively alleviated effects within mechanical sensitivity and depression-like behaviors but may have offered adverse effects in measures of anxiety-like behavior and overall locomotion. Future research should aim to identify the contexts within which these individual models, and their combination, may best replicate the clinical multidimensionality of fibromyalgia.