Department of Anatomy and Histology, Sydney Medical School, University of Sydney, 2006, Australia.
Faculty of Dentistry, University of Sydney, 2006, Australia.
Neuroimage Clin. 2018 Apr 13;19:167-173. doi: 10.1016/j.nicl.2018.04.015. eCollection 2018.
The neural mechanisms underlying the development and maintenance of chronic pain following nerve injury remain unclear. There is growing evidence that chronic neuropathic pain is associated with altered thalamic firing patterns, thalamocortical dysrhythmia and altered infra-slow oscillations in ascending pain pathways. Preclinical and post-mortem human studies have revealed that neuropathic pain is associated with prolonged astrocyte activation in the dorsal horn and we have suggested that this may result in altered gliotransmission, which results in altered resting neural rhythm in the ascending pain pathway. Evidence of astrocyte activation above the level of the dorsal horn in living humans is lacking and direct measurement of astrocyte activation in living humans is not possible, however, there is evidence that regional alterations in T2 relaxation times are indicative of astrogliosis. The aim of this study was to use T2 relaxometry to explore regional brain anatomy of the ascending pain pathway in individuals with chronic orofacial neuropathic pain. We found that in individuals with trigeminal neuropathic pain, decreases in T2 relaxation times occurred in the region of the spinal trigeminal nucleus and primary somatosensory cortex, as well as in higher order processing regions such as the dorsolateral prefrontal, cingulate and hippocampal/parahippocampal cortices. We speculate that these regional changes in T2 relaxation times reflect prolonged astrocyte activation, which results in altered brain rhythm and ultimately the constant perception of pain. Blocking prolonged astrocyte activation may be effective in preventing and even reversing the development of chronic pain following neural injury.
神经损伤后慢性疼痛的发展和维持的神经机制尚不清楚。越来越多的证据表明，慢性神经性疼痛与丘脑放电模式改变、丘脑皮质节律紊乱和上行疼痛通路中慢振荡改变有关。临床前和人体死后研究表明，神经性疼痛与背角中星形胶质细胞的持续激活有关，我们认为这可能导致神经递质传递改变，从而导致上行疼痛通路中静息神经节律改变。目前缺乏活体人类背角以上水平星形胶质细胞激活的证据，也无法直接测量活体人类星形胶质细胞的激活，但有证据表明 T2 弛豫时间的区域改变表明存在星形胶质细胞增生。本研究旨在使用 T2 弛豫测量法来探索慢性或面部神经性疼痛个体中上行疼痛通路的区域脑解剖结构。我们发现，在三叉神经病理性疼痛患者中，脊髓三叉神经核和初级体感皮层以及更高阶处理区域（如背外侧前额叶、扣带回和海马/旁海马皮质）的 T2 弛豫时间降低。我们推测，这些 T2 弛豫时间的区域变化反映了持续的星形胶质细胞激活，从而导致大脑节律改变，并最终导致持续的疼痛感知。阻断持续的星形胶质细胞激活可能有效预防甚至逆转神经损伤后慢性疼痛的发展。
