Preclinical assessment of onabotulinumtoxinA for the treatment of mild traumatic brain injury-related acute and persistent post-traumatic headache.
Preclinical assessment of onabotulinumtoxinA for the treatment of mild traumatic brain injury-related acute and persistent post-traumatic headache.
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DOI：
10.1177/03331024221099841
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发表时间：
2022-10
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在急性和持续性创伤后头痛的小鼠模型中对onabotulinumtoxinA的研究。采用失重法造成轻度颅脑损伤。测量眶周和后爪皮肤异常性疼痛14天。然后将小鼠暴露于强光应激并重新评估异常性疼痛。在不同的损伤后时间点，在颅缝上皮下注射OnabotulinumtoxinA（0.5U）。在Milt创伤性脑损伤后，小鼠表现出持续约14天的眶周和后爪异常性疼痛。在第14-67天，仅在先前受伤的小鼠中通过暴露于应激可以恢复异常性疼痛。在轻度创伤性脑损伤后2小时给予OnabotulinumtoxinA完全阻断了短暂的急性和应激诱导的异常性疼痛，直至第67天。当轻度创伤性脑损伤后72小时给药时，onabotulinumtoxinA逆转了急性异常性疼痛，但只能部分预防应激诱导的异常性疼痛。在第12天，当最初的异常性疼痛基本上得到解决时，OnabotulinumtoxinA给药产生了对应激诱导的异常性疼痛的不完全和短暂的预防。急性异常性疼痛的程度与随后的应激诱发的异常性疼痛呈正相关。轻度创伤性脑损伤诱导短暂的头痛样疼痛，随后是对正常无害的应激刺激的持久敏感性和持续脆弱性，分别模拟急性和持续性创伤后头痛。在急性创伤后头痛消退后给予onabotulinumtoxinA可减少持续性创伤后头痛，但效果是短暂的，表明潜在的持续性轻度创伤性脑损伤诱导的适应不良并未逆转。相比之下，早期onabotulinumtoxinA给药完全阻断了急性创伤后头痛以及向持续性创伤后头痛的转变，这表明预防了促进头痛样疼痛易感性的神经适应。此外，急性创伤后头痛的程度可预测持续性创伤后头痛的风险。
Investigation of onabotulinumtoxinA in a murine model of acute and persistent post-traumatic headache. Mild traumatic brain injury was induced with a weight drop method. Periorbital and hindpaw cutaneous allodynia were measured for 14 days. Mice were then exposed to bright light stress and allodynia was reassessed. OnabotulinumtoxinA (0.5 U) was injected subcutaneously over the cranial sutures at different post-injury time points. After milt traumatic brain injury, mice exhibited periorbital and hindpaw allodynia that lasted for approximately 14 days. Allodynia could be reinstated on days 14–67 by exposure to stress only in previously injured mice. OnabotulinumtoxinA administration at 2 h after mild traumatic brain injury fully blocked both transient acute and stress-induced allodynia up to day 67. When administered 72 h post-mild traumatic brain injury, onabotulinumtoxinA reversed acute allodynia, but only partially prevented stress-induced allodynia. OnabotulinumtoxinA administration at day 12, when initial allodynia was largely resolved, produced incomplete and transient prevention of stress-induced allodynia. The degree of acute allodynia correlated positively with subsequent stress-induced allodynia. Mild traumatic brain injury induced transient headache-like pain followed by long lasting sensitization and persistent vulnerability to a normally innocuous stress stimulus, respectively modeling acute and persistent post-traumatic headache.. Administration of onabotulinumtoxinA following the resolution of acute post-traumatic headache diminished persistent post-traumatic headache but the effects were transient, suggesting that underlying persistent mild traumatic brain injury-induced maladaptations were not reversed. In contrast, early onabotulinumtoxinA administration fully blocked both acute post-traumatic headache as well as the transition to persistent post-traumatic headache suggesting prevention of neural adaptations that promote vulnerability to headache-like pain. Additionally, the degree of acute post-traumatic headache was predictive of risk of persistent post-traumatic headache.
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