Research on humans with Parkinson's disease has shown that chemical changes in the brain cause depression1 and anxiety in patients beyond the depression caused by the physical disabilities associated with the disease. In addition—though often overshadowed by more obvious symptoms such as tremors—pain has been reported in over half of these patients2. It can therefore be deduced that untreated Parkinson's symptoms cause pain and distress in both humans and animals.

The first group of animals receiving MPTP will not have therapeutic intervention to relieve their symptoms. They will receive supportive daily care, but this is not sufficient to be considered Category C because the care will not relieve their pain or distress. These animals should instead be considered Category E.

The other animals fall into a gray area. If it is clear that there is sufficient anesthesia and postsurgical analgesia, then the surgery animals are in the appropriate category (D). In addition, as the induction of Parkinson's disease in these animals does result in a major physiological change, the protocol should be categorized as having multiple major operative procedures for those animals that also undergo stereotaxic surgery.

If the treatments (AAV2 with the gene and AAV2 without the gene) are effective in relieving the symptoms caused by MPTP, then the animals can be safely put in Category D. If these agents are not effective in relieving these symptoms, then these animals too should be in Category E.

The Committee might suggest a small pilot study be done where the parameters of pain and distress are measured in both the MPTP and the treatment groups. This study would also help determine how effective the therapeutic agents are in relieving pain and distress in the animals.

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