Recombinant Herpes Injection into Trigeminal Ganglia

描述（由申请人提供）： 头部癌痛、三叉神经痛、偏头痛、牙痛和颞下颌关节痛都是三叉神经系统特有的疼痛综合征的例子。在许多情况下，这些类型的疼痛很难在临床上治疗，最后一线阿片类药物在某些情况下只起轻微作用，而在其他情况下根本不起作用。此外，强效全身性阿片类药物的耐受性和成瘾潜力有时会限制其有效使用的持续时间。因此，需要新的方法来治疗三叉神经痛。 我们之前已经证明了使用复制缺陷型疱疹病毒构建体来改变疼痛感测神经细胞功能的潜力，这样我们就能够在单次应用后产生强大的，高度局部化的镇痛作用。在此过程中，我们将病毒局部应用于靶组织，如皮肤。这样做，我们已经观察到疼痛反应的非常持久（> 20周）的减弱，仅限于用病毒治疗的那些区域。 然而，在许多三叉神经综合征中，疼痛是相对弥漫性或多中心的。在这些情况下，将载体应用于外周组织的效用可能有限，因为需要更广泛分布的镇痛作用。一种尚未研究的方法是将载体直接注射到三叉神经节中，三叉神经节是构成三叉神经感觉神经细胞体的神经元群。在这样做的过程中，我们希望在广泛分布的三叉神经神经元中引入重组载体，从而潜在地产生广泛的镇痛作用。这里描述的实验将提供证据，以重组疱疹病毒载体，编码基因的镇痛肽，是否直接三叉神经注射将改变由三叉神经支配的组织的伤害性刺激的敏感性。通过这样做，我们希望为三叉神经相关疼痛的新的持久治疗提供初步支持。

DESCRIPTION (provided by applicant): Head cancer pain, trigeminal neuralgia, migraine headache, dental pain and temporomandibular joint pain are all examples of pain syndromes that are unique to the trigeminal system. In many instances, these pain types are hard to treat clinically, with last-line opiates working only marginally well in some instances, and not at all in others. In addition, the tolerance and addiction potential of strong, systemic opioids sometimes limit the duration over which they can be used effectively. Thus, there is a need for novel approaches to the treatment of trigeminal pain. We have previously demonstrated the potential of using replication-defective herpes viral constructs to alter the function of pain-sensing nerve cells, such that we have been able to produce robust, highly localized analgesia for months after a single application. In doing this we have applied the virus locally to targeted tissues, such as skin. Doing so, we have observed a very long-lasting (> 20 weeks) attenuation of pain responses limited to those areas treated with the virus. In many trigeminal syndromes however, pain is relatively diffuse or multicentered. Applications of vectors to peripheral tissues may be of limited utility in these cases, as a more widely distributed analgesic effect is desirable. One method that has not yet been investigated would be to inject vectors directly into the trigeminal ganglia, the grouping of neurons that make up the cell bodies of the sensory nerves of the trigeminal. In doing this, we would expect to introduce recombinant vectors over a wide distribution of trigeminal neurons, and thus, potentially, producing a widespread analgesic effect. The experiments described here will provide evidence as to whether direct trigeminal injection of recombinant herpes vectors, encoding genes for analgesic peptides, will alter the sensitivity to nociceptive stimulation of tissue innervated by the trigeminal. In so doing, we hope to provide initial support for what may be a new long-lasting treatment for trigeminal nerve-related pain.