The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain

INTRODUCTION: Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. METHODS: Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. RESULTS: After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. CONCLUSIONS: Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration

The Asian Economic Crisis and Bureaucratic Development: A Veto Player Analysis

The Asian economic crisis ravaged numerous economies in the late 1990s. Significant social and political disruption followed the fall in Asian currency prices. The newly industrialized states of Asia were particularly hard hit, yet some also experienced swift turnarounds, reaching pre-crisis currency rates and economic output. The enduring puzzle of the crisis is the role of bureaucratic-business ties as a background cause of the crisis and determinant of governmental policy responses. In this paper, we adapt Tsebelis\u27 veto player model to include bureaucracy as a formal actor in the adjustment process. We argue that states that minimized the control of developmental bureaucracies over finance and direct managerial decision-making weakened the institutional capacity of bureaucrats to veto adjustment policies, both before and after the 1997 crisis. Moreover, we find that a tradition of strategic regulatory guidance is associated with favorable economic performance, provided that bureaucrats had subjected private firms or state-owned enterprises to competition (or even business failure) historically, and where the risks associated with financial decisions were not socialized by the state

Characterization of a new animal model for evaluation and treatment of back pain due to lumbar facet joint osteoarthritis

OBJECTIVE: Osteoarthritic (OA) degeneration of the lumbar facet joints has been implicated in low back pain. This study was undertaken to investigate the biologic links between cellular and structural alterations within facet joint components and the development of symptomatic chronic back pain. METHODS: We generated an animal model of facet joint degeneration by intraarticular injection of monosodium iodoacetate (MIA) into facet joints (L3-L4, L4-L5, L5-L6) of Sprague-Dawley rats. Pain sensation due to pressure, which mimics a mechanical stimulus for facet joint injury, was measured using an algometer. Pain response was also assessed in a straight leg raising test. Cartilage alterations were assessed by biochemical evaluation and microfocal computed tomography (micro-CT). Therapeutic modulation of chronic facet joint pain with the use of various pharmacologic agents was investigated. RESULTS: MIA injection resulted in severely damaged facet joint cartilage, proteoglycan loss, and alterations of subchondral bone structure. Micro-CT analyses suggested that the behavioral hyperalgesia from facet joint degeneration was not associated with foraminal stenosis. The biologic and structural changes in facet joints were closely associated with sustained and robust chronic pain. Morphine and pregabalin markedly alleviated pressure hyperalgesia, while celecoxib (a selective inhibitor of cyclooxygenase 2 [COX-2]) produced moderate antihyperalgesic effects and the effect of ketorolac (an inhibitor of COX-1 and COX-2) was negligible. CONCLUSION: Our findings demonstrate that MIA injection provides a useful model for the study of OA changes in the facet joint and indicate that facet joint degeneration is a major cause of chronic low back pain. The treatment results suggest that classes of drugs that are widely used to treat OA, such as nonsteroidal antiinflammatory drugs, may have limited efficacy once joint destruction is complete