Patterns of brain c-Fos expression in response to feeding behavior in acute and chronic inflammatory pain condition

Abstract

Objectives Feeding behavior is known to have potential to alleviate pain. We recently demonstrated that both 24 h fasting and 2 h refeeding (food intake after 24 h fasting) induce analgesia in inflammatory pain conditions via different brain mechanisms. However, brain structures that distinctly involved fasting-and refeeding-induced analgesia is still unknown. Hence, this study is aimed to reveal brain structures mediating fasting-and refeedinginduced analgesia.Methods Mice were given intraplantar (i.pl.) injection of formalin and complete Freund's adjuvant into the left hind paw to induce acute and chronic inflammatory pain, respectively. We examined changes in c-Fos expression with 24 h fasting and 2 h refeeding under acute and chronic inflammatory pain conditions in the contralateral brain. ResultsUnder acute pain condition, c-Fos expression changed with fasting in the anterior cingulate cortex (ACC), central amygdala (CeA), lateral hypothalamus (LH) and nucleus accumbens core (NAcC). Refeeding changed c-Fos expression in the CeA, LH and lateral parabrachial nucleus (lPBN). On the other hand, under chronic inflammatory pain condition, c-Fos expression changed with fasting in the lPBN, medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAcS) while refeeding changed c-Fos expression in the anterior insular cortex, lPBN, mPFC and NAcS. ConclusionThe present results show that brain regions that participated in the fasting-and refeedinginduced analgesia were completely different in acute and chronic inflammatory pain conditions. Also, refeeding recruits more brain regions under chronic inflammatory pain conditions compared to the acute inflammatory pain condition. Collectively, our findings provide novel insights into brain regions involved in fasting-and refeedinginduced analgesia, which can be potential neural circuitbased targets for the development of novel therapeutics.

Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain

“…c‐Fos expression was also used to verify the alteration of ALFF‐nominated brain areas and find abnormal neuronal activity. c‐Fos expression has previously been found to have significant upregulation in the frontal cortex, the third ventricle, hippocampus, and the spinal nucleus of the trigeminal nerve in the medulla after menthol‐stimulated corneal pain in rabbits 20,21 . In line with the rs‐fMRI results, the upregulated mount of c‐Fos verified the abnormal neuronal activity, especially in S2, AID, AIP, AuV, TeA, and Ect in corneal neuropathic pain mice.…”

Anterior Insular-nucleus Accumbens Pathway Controls Refeeding-induced Analgesia under Chronic Inflammatory Pain Condition

“…However, we do not exclude the possibility that other brain regions may also be participated in the refeeding-induced analgesia, as numerous brain regions interact to process pain and feeding behavior [57,58]. Indeed, the whole brain c-Fos analysis shows possible involvement of other brain regions such as the basolateral amygdala, medial prefrontal cortex, lateral parabrachial nucleus, and ventromedial hypothalamus [59]. Future studies of different brain regions will further help us to understand the cellular mechanisms and brain circuits for refeeding-induced analgesia.…”

Dopamine receptor D2, but not D1, mediates the reward circuit from the ventral tegmental area to the central amygdala, which is involved in pain relief

“…Findings have demonstrated that pain relief increased c-Fos expression in the NAc and induced dopamine release in the NAc under acute inflammatory pain conditions. 52,53 In this study, anterograde and retrograde tracing studies demonstrated that VTA dopaminergic neurons were also found to directly project to the CeA. Although there were fewer of these projections than of those projecting to the NAc, we could not exclude a key role for amygdala-projected dopaminergic signaling in pain relief and the affective dimension of pain.…”