Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, CA, USA.
Headache. 2018 Apr;58(4):545-558. doi: 10.1111/head.13248. Epub 2017 Dec 21.
Approximately 1.7 million Americans sustain a traumatic brain injury (TBI) each year and chronic pain is a common complication.
We studied the effects of intranasally administered oxytocin as a potential treatment for chronic pain in an animal model of mild TBI.
The lateral fluid percussion model of mild TBI was chosen for this purpose and after exposure to mild TBI the rats (n = 12) developed hind paw and facial allodynia compared to sham animals (n = 6). Oxytocin or a vehicle was afterwards administered intranasally and reactive pain was assessed by hind paw and facial von Frey testing. Some animals received the oxytocin receptor antagonist, atosiban, in addition to oxytocin/vehicle treatment (n = 12). The effect of oxytocin on ongoing and spontaneous pain was examined through conditioned place preference testing. To determine whether the effects of intranasal oxytocin could be attributed to delivery via the peripheral blood stream, some TBI animals received an intravenous injection of the same oxytocin dose that was given intranasally. ELISA immunoassays were carried out (n = 6) to measure concentrations of oxytocin in the trigeminal ganglia, pons, spinal cord, and olfactory bulb after intranasal administration and evaluate the most likely route of entry.
These studies confirmed that the fluid percussion model can be used to study post-TBI facial allodynia. Oxytocin attenuated both reactive and spontaneous, ongoing non-reactive pain following mild TBI for at least 3-4 hours after intranasal administration by binding to OT or VA1-receptors most likely by a peri-trigeminal nerve mediated uptake.
Intranasal oxytocin attenuates measures of reactive and non-reactive pain in a model of mild TBI and may represent a novel treatment for chronic pain in TBI patients.
每年约有 170 万美国人遭受创伤性脑损伤（TBI），慢性疼痛是常见的并发症。
我们研究了鼻内给予催产素作为轻度 TBI 动物模型中慢性疼痛潜在治疗方法的效果。
为此选择了外侧液体冲击轻度 TBI 模型，并且在暴露于轻度 TBI 后，与假手术动物（n=6）相比，大鼠（n=12）发展出后爪和面部触诱发痛。之后鼻内给予催产素或载体，通过后爪和面部 von Frey 测试评估反应性疼痛。一些动物除了给予催产素/载体治疗之外（n=12）还接受了催产素受体拮抗剂阿托西班治疗。通过条件性位置偏好测试检查催产素对持续性和自发性疼痛的影响。为了确定鼻内给予催产素的效果是否可以归因于通过外周血流传递，一些 TBI 动物接受了与鼻内给予相同剂量的催产素的静脉内注射。进行了 ELISA 免疫测定（n=6）以测量鼻内给予后三叉神经节、桥脑、脊髓和嗅球中的催产素浓度，并评估最可能的进入途径。
这些研究证实，液体冲击模型可用于研究 TBI 后的面部触诱发痛。鼻内给予催产素后，至少在 3-4 小时内，通过与 OT 或 VA1 受体结合，减轻了轻度 TBI 后的反应性和自发性、持续性非反应性疼痛，这很可能是通过三叉神经周围神经介导的摄取来实现的。
鼻内给予催产素可减轻轻度 TBI 模型中反应性和非反应性疼痛的测量值，并且可能代表 TBI 患者慢性疼痛的一种新的治疗方法。
