Effects of diet-induced obesity on motivation and pain behavior in an operant assay

Abstract

Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity prone C57BL/6J mice fed high-fat diet display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity resistant SKH1E mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation.

Abnormal trigeminal sensory processing in obese mice

“…These results are consistent with our previous finding of intact thermal nociception in obese HFD mice. 42 These observations may seem at first to conflict with our current findings in trigeminal neuronal cultures and our previous immunohistochemical findings in the TNc. 41 However, it should be noted that nocifensive wipes may not be sensitive enough to detect subtle differences between the two diet groups.…”

Neurobiology of fibromyalgia and chronic widespread pain

“…Furthermore, the inflammatory cytokine IL-6 primes the muscle to respond in a more long-lasting manner to a subsequent insult, intrmuscular prostaglandin-E2 when compared to naive animals injected with prostaglandin-E2 (Dina et al, 2008), and the inflammatory cytokines may also underlie the stress-induced enhancement of muscle pain described above (Dina et al, 2011b). Another potential source of such cytokines is adipose tissue, and there are many studies now begining to suggest that widespread or multifocal pain is more common in obese individuals (Cicuttini and Wluka, 2016), and obese animals show enhanced nociceptive responses (Rossi et al, 2013a, Rossi et al, 2013b). Thus, pro-inflammatory cytokines might play a role in the generation and enhancement of chronic muscle pain including fibromyalgia.…”

Decrease in Operant Responding Under Obesogenic Diet Exposure is not Related to Deficits in Incentive or Hedonic Processes

“…Supporting this hypothesis, some studies in both human subjects and rodent models have shown that obesity is associated with alterations in some markers of mesolimbic DA signaling. This correlates with the preference of subjects with obesity for immediate food access versus a delayed, though larger, food reward and the decreased performance in motivational tasks (motivation being defined as the amount of effort the animal is willing to expend to obtain a reward) in rodents exposed to obesogenic diets .…”

“…However, the very nature of the alteration of mesolimbic DA transmission in subjects with obesity has been recently challenged, and data in animal models are inconsistent . Regarding behavioral alterations in rodents under an obesogenic diet, some studies have shown a reduction in the willingness to work for food reinforcers , while others have found an increase . Motivation in rodent models is largely tested through the willingness to exert effort for food reinforcers in operant tasks; however, it is not clear whether alterations in performance mainly reflect a change in incentive processes.…”