Pain is a subjective, private, yet universal phenomenon that depends on a unique combination of sensory, affective, and evaluative characteristics. Although preclinical models have been used to understand much of pain physiology, the inability to communicate with animals limits affective and evaluative feedback and has constrained traditional behavioral methods to adequately represent and study the multidimensional pain experience. Therefore, this study sought to characterize the affective component of pain within a novel operant approach-avoidance paradigm (AAP) to determine which type of pain (inflammatory and neuropathic) may be more aversive. To reveal the possible differences in pain aversiveness within the AAP paradigm, animals received bilateral inflammatory and neuropathic pain conditions and were given the choice to a) forgo appetitive reward by not receiving noxious stimulus of either inflammatory or neuropathic conditions or b) receive noxious stimulus in exchange for an appetitive reward. Although all pain conditions produced significant hypersensitivity, the AAP results revealed there was no preference in the stimulation of a specific paw in the bilateral pain conditions. The finding suggests that despite unique clinical pain characteristics for inflammatory and neuropathic conditions, the lack of observable differences in the pain conditions may not necessarily equate to the overall similarity in aversiveness, but rather that the fixed ratio (FR1) paradigm presentation allowed appetitive reward to be more salient, highlighting the complexities of competing motivational drives of pain and hunger when satiating hunger is always guaranteed. Thus, future studies should seek to further tease apart this relationship with a different schedule and food-controlled methodologies. The development of such preclinical approaches can thoroughly investigate the intricacy of competing drives and likely reveal important information regarding the complexity of pain, enhancing our understanding of pain perception in individuals suffering from comorbid pain states.
Fibromyalgia (FM) is a chronic, widespread pain disorder generally of a non-inflammatory nature with many known affective and cognitive comorbidities. There is promise in the implementation of hyperbaric oxygen therapy (HBO2) for alleviating FM pain and comorbidities, despite no work investigating the efficacy of this treatment in prominent preclinical FM models. This project aimed to investigate the affective components, specifically anhedonia and anxiety, associated with an acidic saline model of FM in rats. We investigated the acidic saline model's ability to produce the sensory component of FM through reduced mechanical thresholds, as well as anxiety-like and avoidance behaviors through measures of open field and place escape/avoidance. We further investigated the use of pregabalin, a known FM therapeutic agent, in reducing negative sensory and affective measures within the model. Results revealed insignificant between-group differences for measures of anxiety, despite animals in the FM condition showing significantly reduced mechanical thresholds. Results further revealed that the acidic saline model was effective in increasing place escape/avoidance behavior among animals in the FM condition, with pregabalin reducing avoidance behaviors. In addition, we investigated the role of HBO2 [two 60-minute treatments at 2.0 ATA (atmospheres absolute)] in alleviating FM-like pain, anxiety, and anhedonia in the acidic saline model, utilizing mechanical paw withdrawal thresholds, open field, and sucrose preference measures. Results revealed that the acidic saline model produced reduced thresholds indicative of FM-like pain. Data did not provide support for the presence of anxio-depressive comorbidities associated with the FM model. HBO2 treatment did not significantly increase mechanical thresholds as expected. Future studies should seek to investigate the experimental circumstances within which the acidic saline model produces negative affect alongside hyperalgesia in order to contribute to the development of a multidimensional FM treatment methodology.
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