三叉神经节嘌呤能受体亚型 P2X3 的上调参与了咬合干扰诱导的大鼠口腔疼痛。

Upregulation of the Purinergic Receptor Subtype P2X3 in the Trigeminal Ganglion Is Involved in Orofacial Pain Induced by Occlusal Interference in Rats.

出版信息

J Oral Facial Pain Headache. 2016 Winter;30(1):51-60. doi: 10.11607/ofph.1459.

Abstract

AIMS

To evaluate whether the purinergic receptor subtype P2X3 (P2X3R) in trigeminal ganglion (TG) neurons is involved in hyperalgesia of the temporomandibular joints (TMJs) and masseter muscles associated with placement of an occlusal interference.

METHODS

Forty-five rats were randomized into five groups (ie, for days 1, 3, 7, 14, or 28; nine rats per group). Six rats from each group were chosen to receive the occlusal interference, and the remaining three rats were sham-treated controls. On days 1, 3, 7, 14, and 28 after placement of the occlusal interference, the mechanical pain threshold (MPT) to stimulation of the TMJs or masseter muscles was examined using von Frey filaments. Seven days after the occlusal interference placement, changes in MPT were tested after administration of the P2X3R antagonist A-317491 into the TMJs and masseter muscles (60 μg/site) in six rats. The expression of P2X3R in the TGs was investigated by immunohistochemistry and quantitative polymerase chain reaction (qPCR). Retrograde tracing was combined with immunofluorescence to identify TMJ and masseter muscle afferent neurons in the TGs of six premature rats.

RESULTS

The TMJ and masseter muscle MPTs were decreased after placement of the occlusal interference, and the P2X3R antagonist reversed the mechanical hyperalgesia that was caused by the occlusal interference placement. The frequency of P2X3R-immunoreactive cells increased in small-sized neurons in the TG after occlusal interference. By contrast, there was no increase in medium-sized TG neurons. P2X3R mRNA increased on day 3. Retrograde tracing indicated that the TMJ and masseter muscle afferent neurons in the TG expressed P2X3R.

CONCLUSION

Upregulated P2X3R expression in the TG may contribute to orofacial pain development induced by an occlusal interference. P2X3R may be a therapeutic target for chronic TMJ or masseter muscle pain.

摘要

目的

评估三叉神经节（TG）神经元中的嘌呤能受体亚型 P2X3（P2X3R）是否参与与放置咬合干扰相关的颞下颌关节（TMJ）和咀嚼肌的痛觉过敏。

方法

45 只大鼠随机分为 5 组（即第 1、3、7、14 或 28 天；每组 9 只大鼠）。每组的 6 只大鼠接受咬合干扰，其余 3 只大鼠作为假手术对照。在放置咬合干扰后的第 1、3、7、14 和 28 天，使用 von Frey 细丝检查 TMJ 或咀嚼肌刺激的机械痛阈（MPT）。在放置咬合干扰后的第 7 天，在 TMJ 和咀嚼肌（60 μg/部位）中给予 P2X3R 拮抗剂 A-317491 后，测试 MPT 的变化。在 6 只早产大鼠的 TG 中，将逆行示踪与免疫荧光相结合，以鉴定 TMJ 和咀嚼肌传入神经元。

结果

放置咬合干扰后 TMJ 和咀嚼肌 MPT 降低，P2X3R 拮抗剂逆转了咬合干扰引起的机械性痛觉过敏。咬合干扰后，TG 中小神经元中 P2X3R 免疫反应性细胞的频率增加，而中型 TG 神经元没有增加。P2X3R mRNA 在第 3 天增加。逆行示踪表明，TG 中的 TMJ 和咀嚼肌传入神经元表达 P2X3R。