A single dose of anti-NGF antibody exerts a long-lasting analgesic effect on pain during motion in a rat model of OA. This finding could be associated with the analgesic efficacies that anti-NGF antibodies have exhibited in clinical studies. It appears unlikely that analgesia is secondary to inhibition of joint edema and lesion.

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A non-subjective automated method for measuring spontaneous pain behaviour in an animal model of neuropathic pain was established. It is expected that the current system will greatly enhance the analysis of spontaneous pain-related behaviour, which is a predominant symptom in patients with neuropathic pain. The current system may also be valuable in the screening of potential analgesic treatments.

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Immunoreceptor tyrosine-based activation motif (ITAM) plays an important role in signal transduction through mammalian T-cell and B-cell antigen receptors and Fc receptors. The ITAM has been found only in vertebrate immunocytes. Ascidians are intriguing invertebrates from the viewpoint of the evolution of immune systems because they are considered to be ancestors of the vertebrates. We have previously shown that the monoclonal antibody A74 inhibits cellular defense reactions of the ascidian. In the present studies, we found that the A74 antigen protein has two ITAMs and several motifs that are proposed to function in signal transduction. The A74 protein is tyrosine-phosphorylated and associated with other proteins in the initial stages of cellular defense reactions. The ITAMs of the A74 protein are tyrosine-phosphorylated by a c-Src kinase in vitro. The A74 protein provides a key to the understanding of the origin of vertebrate immune systems.The understanding of innate immunity of protochordates, which occupy a phylogenetic position between vertebrates and true invertebrates and therefore are considered to be ancestors of the vertebrates, provides new insights into the origin and the evolution of acquired immunity of vertebrates. Hemocytes (i.e. immunocytes present in hemolymph) play important roles in host defense of invertebrates (1). In the ascidian Halocynthia roretzi, the hemocytes undergo several cellular defense reactions including phagocytosis and hemocyte aggregation (2).Monoclonal antibodies that inhibit the cellular defense reactions in H. roretzi have been utilized to define hemocyte membrane-bound molecules that are involved in these reactions (2). The monoclonal antibody A74 inhibits phagocytosis of foreign substances by hemocytes and also aggregation of hemocytes (2, 3); the former reaction is triggered by hemocyte-foreign substance interaction (3), whereas the latter is triggered by hemocyte-hemocyte interaction (4). We purified the A74 antigen protein from H. roretzi hemocytes and found that it is a novel membrane glycoprotein with a molecular mass of 160 kDa (3); the molecular mass of its protein portion is approximately 90 kDa.In this paper we report the cloning of the A74 protein. We found that the A74 protein has two (one typical and one nontypical) ITAMs, 1 which have been reported to play important roles in signal transduction through mammalian TCR, BCR, and FcRs (5, 6). We also demonstrated that the ITAMs of the A74 protein are tyrosine-phosphorylated by a c-Src kinase. To our knowledge, this is the first finding concerning ITAM in invertebrates. EXPERIMENTAL PROCEDUREScDNA Cloning-The N-terminal amino acid sequence (3) of ascidian A74 protein was used to design degenerate oligonucleotide primers for PCR (5Ј-GC(T/C/A)GT(T/C/A/G)AC(T/C/A/G)CA(A/G)(A/C)G(T/C/A/G)-CA(A/G)GC-3Ј and 5Ј-GG(A/G/C/T)A(A/G)(A/T)CC(A/G/C/T)GC(A/G/C/T)-A(A/G)(A/G/C/T)GT(A/G/T)GC-3Ј). The primers at concentrations of 10M were mixed in PCR to amplify the H. roretzi hemocyte cDNA library. PCR was done in 10 mM Tris-HC...