Patients with Complex Regional Pain Syndrome, type I (CRPS-I), formerly termed Reflex Sympathetic Dystrophy, have chronic, post-traumatic pain that spreads beyond the distribution of any single peripheral nerve without evidence of major peripheral nerve damage. A similar disorder, Causalgia, re-named CRPS-II, presents with clear evidence of nerve injury. No successful drug treatment exists for these disorders. Neurotropin is a non-protein extract of cutaneous tissue from rabbits inoculated with vaccinia virus. Neurotropin tablets, prepared from the tissue extract, have been used extensively in Japan to treat CRPS and other painful conditions;however, the drug has not undergone clinical therapeutic testing in the United States. Protocol (00-NR-0200) was designed to carry out double-blind, placebo-controlled, crossover studies about clinical efficacy of Neurotropin (FDA IND # 60,994) for chronic neuropathic pain in outpatients with CRPS-I or II. Subjects of this double blind cross-over study receive Neurotropin or placebo tablets for 5 weeks, then no trial medication for at least 1 week, and then the other trial drug for the next 5 weeks. That is, patients who took placebo the first 5 weeks will take Neurotropin the second 5 weeks and vice versa. Thirty male and female patients (age range: 18 and older) meeting the diagnostic criteria established by the International Association for the Study of Pain for diagnosis of CRPS who have been treated unsuccessfully with a current standard therapeutic regimen will be selected for the study. The CRPS patients are given the test drug (4 tablets, twice daily) orally for 5 weeks. After the washout period (at least 1 week), the other test drug was administered to the same patient. Before first treatment phase and after 5 weeks of each treatment phase, the pain sensation (area, spontaneous pain intensity, allodynia, hyperalgesia), quality of life (SF-36 questionnaire), autonomic function (skin color, skin blood flow and temperature), edema/swelling of affected limb, and active range of motion of involved joints are measured. Twelve patients have completed the study. Since the beginning in October 2000, we have screed about 350 patients who were referred with a diagnois of CRPS. However, most participants were in chronic stage of CRPS and/or symptoms to both sides of the body, and therefore did not meet the inclusion criteria for the study, three patients have been dropped from the study. There were no adverse effects related to test drugs in any of the patients who have completed the study. All of these patients elected to have the optional additional 5-week treatment with the agent that they thought had a beneficial effect. However, because the code of this study drug has not been broken we do not know how often the placebo or the putative active drug was chosen. In order to expedite the patient enrollment to the study, we allowed inclusion for screening patients formerly excluded because the injury involved a proximal region, such as the unilateral shoulder or inguinal region. However, we will keep unchanged the inclusion criteria for the limb regions demonstrating the typical signs and symptoms of CRPS. We also increased our efforts in reaching physicians and other professionals who treat CRPS patients and made more widely available information regarding this study using sponsored internet links on search engines. Recently, one male patient was enrolled in the study. The continuation of this study was approved by the CNS IRB in September 2008. A parallel protocol is evaluating the use of neurotropin for fibromyalgia (FM), a disabling disorder that primarily affects women and presents a therapeutic challenge. Because of the reported efficacy of Neurotropin for treatment of FM in Japan, we have planned a double-blind, placebo-controlled, crossover studies to confirm these reports. The study is designed to test whether Neurotropin treatment will affect spontaneous pain, sensitivity to pressure-induced pain at specific locations, and/or the ability of the patient to function in normal activities as well as affect the fatigue, sleep disturbance, anxiety and mood disorder frequently seen in fibromyalgia patients. Female patients (age range: 18 and older) meeting the criteria established by the American College of Rheumatology for diagnosis of FM who have been treated unsuccessfully with a current standard therapeutic regimen are selected for the study. The criteria are (A) a history of widespread pain (in all quadrants and back) for more than half of the days in each of the prior three months and (B) the required number (11) of tender points of 18 test sites, which will be determined during the initial physical examination. The average score on the Fibromyalgia Impact Questionnaire (FIQ: a brief 10-item self-administered measure of physical functioning, ability to work and perform activities of daily living, depression, anxiety, sleep, pain, stiffness and fatigue) for patients seen in tertiary care settings is about 50 (with 100 being the maximum, a higher score indicating a greater impairment of health) and we will include only those patients in whom the FIQ score is greater than 30 at the initial evaluation. To be admitted to this study, patients must be willing to continue using only their present medications (including antidepressants) or other forms of care related to the control of FM symptoms during the course of the study. Because Neurotropin may take several weeks to have an effect and because FM has such a spontaneously fluctuating course, in this study test tablets will be administered over a 12-week interval. Neurotropin or matching placebo will be randomly assigned as the first treatment. During the first 12-week treatment patients will be given Neurotropin or placebo tablets. After more than 1 week wash-out period, the patient will receive a second 12-week supply of placebo (for those patients who received Neurotropin tablets) or Neurotropin tablets (for those patients who received placebo tablets). In both treatment phases, the patient is instructed to take 8 tablets daily (4 tablets twice daily), the dosage used in Japan and in another NIH protocol (00-NR-0200) for clinical trial of Neurotropin in patients with CRPS. Before each treatment phase and every 6 week during each treatment phase, the FIQ, SF-36, the manual tender point count, the dolorimetric estimate of overall tenderness and the six minute walk test are measured. Differences in the FIQ scores during and at the end of the study period will be used as the primary outcome measure. The 18 (9 bilateral) specified locations are examined for tender points. The dolorimetric measurement of mean pressure thresholds to elicit pain determined at three paired points (epicondyle, mid-trapezius, and thumbnail) assesses overall tenderness. The continuation of this study (06-NR-0229) was approved by the NIAMS/NIDDK IRB in March 2008. since the initiation of the study, nine patients enrolled in the study, and 4 patients have completed the study, three patients are currently on the first phase medication. Two patients have been dropped from the study. There were no adverse effects related to the test drugs in any of the patients. We anticipate that this study may require 2-3 years to complete.