Title Prolonged gabapentin analgesia in an experimental mouse model offibromyalgia

In a new mouse model for generalized pain syndrome, including fibromyalgia, which used intermittent cold stress (ICS), bilateral allodynia in the hindpaw was observed that lasted more than 12 days; thermal hyperalgesia lasted 15 days. During constant cold stress (CCS), mice showed only a transient allodynia. A female prevalence in ICS-induced allodynia was observed in gonadectomized but not in gonad intact mice. Systemic gabapentin showed complete anti-allodynic effects in the ICS model at the one-tenth dose for injury-induced neuropathic pain model, and central gabapentin showed long-lasting analgesia for 4 days in ICS, but not the injury model. These results suggest that the ICS model is useful for the study of generalized pain syndrome. Findings Fibromyalgia syndrome (FMS) is a highly prevalent (~2% of all citizens) chronic pain disease, which has unique characteristics including generalized or widespread allodynia and a female preponderance [1-4]. According to recent reports, physical and psychological stressors are believed to trigger FMS [5-9]. Although there are several trials underway to make existing medicines available for FMS treatment, attempts to develop a compound specific for FMS are yet to be performed. One reason is the lack of established experimental animal models for FMS, although several models have been proposed [10-13]. Here, we report a pharmacological study using a new generalized chronic pain or FMS model, using intermittent cold stress. We improved the mouse model for dysautonomia, also referred to as the specific alternation of rhythm in temperature (SART) model [14,15]. To develop the stress model of mice with reproducible and long-lasting allodynia and hyperalgesia, we evaluated several different stress paradigms. With regard to a temperature of the cold room, the temperature of 4 ± 2°C gave rise to long-lasting allodynia. At the temperature over 6°C, long-lasting and stable allodynia was not observed. For quick changes in temperature between 4 and 24°C, we used a meshed stainless steel floor in each cage, and transferred mice individually, leaving the stainless floor in the cold room. Trials with different numbers of mice in the same cage, ranging from one to eight mice, revealed that the number of mice in the same cage should be two. Although frequent temperature change is expected to be more stressful, an interval of more than 30 min was estimated to be minimal for the switch between 4 and 24°C. To maintain healthy conditions in the cold room, food pellets and gelatin as the water supply were placed on the floor of the cage in the cold room, owing to the lowered spontaneous activities of mice in such conditions. For stable nociception, an adaptation period of at least 1 h before the nociception tests was necessary. Published: 6 November 2008 Molecular Pain 2008, 4:52 doi:10.1186/1744-8069-4-52 Received: 14 October 2008 Accepted: 6 November 2008 This article is available from: http://www.molecularpain. com/content/4/1/52 © 2008 Nishiyori and Ueda; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Molecular Pain 2008, 4:52 http://www.molecularpain. com/content/4/1/52