this proposal will complete preclinical toxicity testing and safety assessment of i.t. Amitriptyline. We will test its effect on acute nociceptive pain alone, its interaction with iv alfentanil in acute nociceptive pain, and its efficacy alone against intradermal capsaicin-induced hyperalgesia and allodynia in humans. These effects will be correlated with CSF neurotransmitter and amitrip-tyline concentrations to provide presumptive evidence for mechanisms in humans.