Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Analgesic Effects of Intra-Articular Botulinum Toxin Type B (BoNT B) in a Murine Model of Chronic Degenerative Knee Arthritis Pain
Anderson1, Stephanie R., McGarraugh2, Pari, Frizelle2, Sandra, Krug2, Hollis E., Mahowald1, Maren L.
Studies have shown joint inflammation may cause peripheral and central sensitization of neurons leading to spontaneous joint pain at rest and hyperalgesia with stimulation. Inflammatory mediators induced by neuropeptide release activate peripheral nerve receptors. Given this peripheral sensitization we hypothesize arthritis pain may be treated by intra-articular (IA) neurotoxins. Efficacy of IA botulinum toxin (BoNT) Type A for refractory arthritis pain has recently been reported, prompting interest in screening other botulinum toxins that may prove more effective for arthritis pain. BoNT B may produce greater pain relief and may be effective in different types of pain than BoNT A. We hypothesized that BoNT B would reduce chronic arthritic knee pain and tested this hypothesis in a murine model of chronic degenerative arthritis.
Chronic arthritis was produced in 12 C57Bl6 mice by IA injection of 10 IU Collagenase. BoNT B (MYOBLOC) 0.02 was given IA in the left knee 3 days before testing. Normal right knee served as internal control. Mice were studied before, after induction of arthritis and after IA BoNT B. Video gait analysis was performed using Treadscan hardware and software.Evoked pain behavior was measured by tallying fights + vocalizations/1 min in response to repeated firm palpation of the knee. Gait and strength were observed visually and graded. Strength was measured as ability to grasp and cling. Student's t-test was used for statistical comparisons.
|BASELINE Mn (SEM)||ARTHRITIC Mn (SEM)||P c/w Baseline||TREATED Mn (SEM)||P c/w Arthritic|
|Gait||3.50 (.17)||2.08 (.14)||0.0001||3.33 (.15)||<0.0001|
|Evoked Pain Response||1.83 (.81)||5.50 (1.14)||0.0009||3.58 (.87)||0.21|
|Variability in Stance/Stride||.102 (.007)||.126 (.009)||0.003||.099 (.006)||0.02|
|Variability in Lt Rear Propel time||62.8 (4.36)||75.0 (2.49)||0.02||63.7 (3.36)||0.02|
|Variability in Rear Tract Width||2.76 (.26)||3.37 (.28)||0.03||2.55 (.19)||0.02|
|Grasp||3.83 (.07)||2.54 (.38)||0.007||3.12 (.16)||0.11|
|Cling||3.66 (.13)||2.7 (.37)||0.04||3.04 (.27)||0.53|
Chronic degenerative arthritis pain can be quantitated in a murine model using visual and computerized gait analysis, and evoked pain scores. Visual and computerized gait analysis both showed a significant impairment in gait in arthritic mice, improving after IA BoNT B suggesting a substantial analgesic effect. Evoked pain responses increased overall with arthritis, decreasing with IA BoNT B, but not reaching statistical significance in this small sample.
These results support the hypothesis that chronic arthritis pain is amplified by neuropeptide release in the periphery due to efferent neurogenic signals. Interruption of neuropeptide release by IA BoNT B appeared to decrease pain behaviors and improve gait abnormalities. No limb weakness was noted. These results support further investigation of this novel approach to treatment of arthritis pain with IA neurotoxin.
To cite this abstract, please use the following information:
Anderson, Stephanie R., McGarraugh, Pari, Frizelle, Sandra, Krug, Hollis E., Mahowald, Maren L.; Analgesic Effects of Intra-Articular Botulinum Toxin Type B (BoNT B) in a Murine Model of Chronic Degenerative Knee Arthritis Pain [abstract]. Arthritis Rheum 2009;60 Suppl 10 :843