Recombinant Herpes Injection into Trigeminal Ganglia

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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.