Recombinant Herpes Injection into Trigeminal Ganglia

描述(由申请人提供)： 头癌痛、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，这些疼痛类型很难临床治疗，最后一线阿片类药物在某些情况下只有轻微的效果，在另一些情况下则根本不起作用。此外，强的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疱疹病毒结构来改变痛感神经细胞的功能的潜力，这样我们就能够在单一应用后的几个月内产生强大的、高度局部性的止痛。在这样做的过程中，我们已经将病毒局部应用于目标组织，如皮肤。这样做，我们观察到仅限于那些接受病毒治疗的区域的疼痛反应有非常长时间(20周)的减弱。 然而，在许多三叉神经症候群中，疼痛相对弥漫或多中心。在这些情况下，将载体应用于周围组织可能用处有限，因为需要更广泛分布的止痛效果。一种尚未被研究的方法是将载体直接注入三叉神经节，三叉神经节是组成三叉神经感觉神经细胞体的一组神经元。在这样做的过程中，我们希望将重组载体引入广泛分布的三叉神经细胞，从而潜在地产生广泛的止痛效果。这些实验将为三叉神经直接注射编码止痛肽基因的重组疱疹病毒载体是否会改变三叉神经支配的组织对伤害性刺激的敏感性提供证据。通过这样做，我们希望为三叉神经相关疼痛的新的长期治疗提供初步支持。

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.