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

Abstract

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.

Figure 1

The histological analysis of MIA-injected L4/L5 FJ (7 wk post-surgery). A. L4/L5 FJ was sectioned horizontally and stained with Safranin-O. Bar is 1.0 mm. B & C. Magnified L4/L5 FJ stained with Safranin-O (100X) (B) and stained with H & E (100X) (C). D. Immunohistological analysis with CD11b.

Figure 2

Three-dimensional µCT scans of subchondral bone of MIA-induced FJs. A. Cranial view and B. Cross-sectional image of µCT (a) contralateral intact control and (b) MIA-induced FJ L4/L5. C. Lateral view of FJ (a) MIA (0.02mg)-injected and (b) contralateral intact normal.

Figure 3

Behavioral pain assessment over a 7-wk time course by measurement of the vocalization threshold using a pressure algometer. MIA-injected ipsilateral FJ animals had greater ipsilateral pain sensitivity (*) than on the contralateral side, and more pain sensitivity than animals with sham surgery FJs. Data are presented as mean ±SEM.

Figure 4

The analysis of foraminal stenosis on three-dimensional microCT images. A, foraminal height on transverse plan; B, foraminal width on coronal plan; C, foraminal width on lateral view; D, the measurement of foraminal size alteration between contralateral FJ and MIA-injected ipsilateal FJ (n=7).

Figure 5

Measurement of the vocalization threshold using a pressure algometer test to examine pharmacological efficacy of drugs on FJ pain (up to 24 hr). A. Systemic administration of morphine, celecoxib and ketorolac by either oral gavage or intraperitoneal injection followed by primary pressure pain assessment by algometer. *Morphine provided more pain relief than all other COX inhibitor drugs tested; #celecoxib produced a moderate anti-hyperalgesic effect. B. Dose-dependent anti-hyperalgesic effects by oral administration of pregabalin (5, 10 and 20 mg/kg) followed by behavioral pain assessment by algometer. *Potent anti-hyperalgesic effect at the higher doses of pregabalin (10 and 20 mg/kg). Data are presented as mean ±SEM. N=12 for each group.