{'fraction_non_alphanumeric': 0.047123287671232875, 'fraction_numerical': 0.03452054794520548, 'mean_word_length': 5.592057761732852, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Red nucleus interleukin‐1β evokes tactile allodynia through activation of JAK/STAT3 and JNK signaling pathways

We previously reported that interleukin‐1β (IL‐1β) in the red nucleus (RN) is involved in pain modulation and exerts a facilitatory effect in the development of neuropathic pain. Here, we explored the actions of signaling pathways, including the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), c‐Jun N‐terminal kinase (JNK), extracellular signal‐regulated kinase (ERK), p38 mitogen‐activated protein kinase (p38 MAPK) and nuclear factor‐κB (NF‐κB) pathways, on RN IL‐1β‐mediated pain modulation. After a single dose of recombinant rat IL‐1β (rrIL‐1β, 10 ng) injected into the RN in normal rats, a tactile allodynia was evoked in the contralateral but not ipsilateral hindpaw, commencing 75 min and peaking 120 min postinjection. Up‐regulated protein levels of phospho‐STAT3 (p‐STAT3) and p‐JNK were observed in the RN 120 min after rrIL‐1β injection, the increases of p‐STAT3 and p‐JNK were blocked by anti‐IL‐1β antibody. However, the expression levels of p‐ERK, p‐p38 MAPK, and NF‐κB in the RN were not affected by rrIL‐1β injection. RN neurons and astrocytes contributed to IL‐1β‐evoked up‐regulation of p‐STAT3 and p‐JNK. Further studies demonstrated that injection of the JAK2 antagonist AG490 or JNK antagonist SP600125 into the RN 30 min prior to the administration of rrIL‐1β could completely prevent IL‐1β‐evoked tactile allodynia, while injection of the ERK antagonist PD98059, p38 MAPK antagonist SB203580, or NF‐κB antagonist PDTC did not affect IL‐1β‐evoked tactile allodynia. In conclusion, our data provide additional evidence that RN IL‐1β is involved in pain modulation, and that it exerts a facilitatory effect by activating the JAK/STAT3 and JNK signaling pathways.