Department of Brain and Cognitive Sciences, College of Natural Sciences.
Tooth-Periodontium Complex Medical Research Center, School of Dentistry.
Neuroreport. 2021 Oct 13;32(15):1269-1277. doi: 10.1097/WNR.0000000000001723.
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 refeeding-induced analgesia.
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.
Under 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.
The present results show that brain regions that participated in the fasting- and refeeding-induced 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 refeeding-induced analgesia, which can be potential neural circuit-based targets for the development of novel therapeutics.
已知进食行为具有缓解疼痛的潜力。我们最近的研究表明，在炎症性疼痛条件下，24 小时禁食和 2 小时再喂养（禁食 24 小时后进食）通过不同的大脑机制诱导镇痛。然而，参与禁食和再喂养诱导镇痛的大脑结构仍不清楚。因此，本研究旨在揭示介导禁食和再喂养诱导镇痛的大脑结构。
在左后爪中给小鼠注射福尔马林和完全弗氏佐剂，分别诱发急性和慢性炎症性疼痛。我们检查了在急性和慢性炎症性疼痛条件下，24 小时禁食和 2 小时再喂养时，对侧大脑中 c-Fos 表达的变化。
在急性疼痛条件下，禁食时 c-Fos 表达在扣带前皮质（ACC）、中央杏仁核（CeA）、外侧下丘脑（LH）和伏隔核核心（NAcC）中发生变化。再喂养时，c-Fos 表达在 CeA、LH 和外侧臂旁核（lPBN）中发生变化。另一方面，在慢性炎症性疼痛条件下，禁食时 c-Fos 表达在 lPBN、内侧前额叶皮质（mPFC）和伏隔核壳（NAcS）中发生变化，而再喂养时 c-Fos 表达在岛叶前皮质、lPBN、mPFC 和 NAcS 中发生变化。
本研究结果表明，在急性和慢性炎症性疼痛条件下，参与禁食和再喂养诱导镇痛的大脑区域完全不同。此外，与急性炎症性疼痛条件相比，慢性炎症性疼痛条件下再喂养会募集更多的大脑区域。总之，我们的研究结果为参与禁食和再喂养诱导镇痛的大脑区域提供了新的见解，这些区域可能是新型治疗药物开发的潜在神经回路靶点。
