The analgesic effect of intraarticular OnabotulinumtoxinA in a female murine model of collagenase induced chronic degenerative monoarthritis

Nicole Blanshan; Maren L. Mahowald; Christopher Dorman; Sandra Frizelle; Hollis E. Krug

doi:10.1016/j.toxicon.2018.11.307

The analgesic effect of intraarticular OnabotulinumtoxinA in a female murine model of collagenase induced chronic degenerative monoarthritis

Nicole Blanshan, Maren L. Mahowald, Christopher Dorman, Sandra Frizelle, Hollis E. Krug

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Purpose: We previously reported the efficacy of intraarticular (IA) rimabotulinumtoxinB (BoNT/B) in a murine model of chronic degenerative arthritis pain. This study aimed to measure the analgesic effects of onabotulinumtoxinA (BoNT/A) on collagenase induced chronic degenerative arthritis joint pain. Methods: Chronic degenerative arthritis was produced by IA injection of 10 μl collagenase (Col) (10 IU) into the left knee of C57BL/6J female mice 4 weeks prior to pain assessment. IA BoNT/A was injected 3 days before testing. Arthritis pain was measured as evoked pain scores (EPS) and spontaneous pain behaviors with an advanced dynamic weight bearing (ADWB) device. EPS was a tally of fights and vocalizations exhibited in one minute with knee palpation. Percent body weight and percent time spent on each limb was quantified. All mice were 12 weeks old at the time of examination. Results: IA Col increased EPS and reduced ADWB measures of percent weight bearing on the left hind limb compared to naïve mice. BoNT/A treatment reduced EPS and increased weight bearing on the left hind limb. The improvements were not significant compared to the Col group. There was no significant difference in time spent on the left hind limb between any treatment groups. Forelimb ADWB measures of percent weight and time in arthritic mice significantly increased compared to nonarthritic animals. Treatment with BoNT/A in the arthritic limb decreased this offloading; however, statistical analysis only showed significance in weightbearing. Conclusion: IA Col monoarthritis increased evoked and spontaneous pain behaviors in female mice after four weeks. Treatment with IA BoNT/A decreased pain behaviors but only forelimb weight bearing showed a significant improvement. This led us to conclude that treatment with BoNT/A is not an effective analgesic for the treatment of chronic degenerative knee arthritis in murine models.

Original language	English (US)
Pages (from-to)	8-15
Number of pages	8
Journal	Toxicon
Volume	158
DOIs	https://doi.org/10.1016/j.toxicon.2018.11.307
State	Published - Feb 2019

Bibliographical note

Funding Information:
This work was supported by Merit Review Award #RX000379-05 from the US Department of Veterans Affairs Rehabilitation Research and Development Service . The contents do not represent the views of the US department of Veterans Affairs or the United States Government.

Publisher Copyright:
© 2018 The Authors

Keywords

Botox™
Mouse
Neurotoxins
Osteoarthritis
Pain

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@article{57824dc400f74aad9a08f31505de1791,

title = "The analgesic effect of intraarticular OnabotulinumtoxinA in a female murine model of collagenase induced chronic degenerative monoarthritis",

abstract = "Purpose: We previously reported the efficacy of intraarticular (IA) rimabotulinumtoxinB (BoNT/B) in a murine model of chronic degenerative arthritis pain. This study aimed to measure the analgesic effects of onabotulinumtoxinA (BoNT/A) on collagenase induced chronic degenerative arthritis joint pain. Methods: Chronic degenerative arthritis was produced by IA injection of 10 μl collagenase (Col) (10 IU) into the left knee of C57BL/6J female mice 4 weeks prior to pain assessment. IA BoNT/A was injected 3 days before testing. Arthritis pain was measured as evoked pain scores (EPS) and spontaneous pain behaviors with an advanced dynamic weight bearing (ADWB) device. EPS was a tally of fights and vocalizations exhibited in one minute with knee palpation. Percent body weight and percent time spent on each limb was quantified. All mice were 12 weeks old at the time of examination. Results: IA Col increased EPS and reduced ADWB measures of percent weight bearing on the left hind limb compared to na{\"i}ve mice. BoNT/A treatment reduced EPS and increased weight bearing on the left hind limb. The improvements were not significant compared to the Col group. There was no significant difference in time spent on the left hind limb between any treatment groups. Forelimb ADWB measures of percent weight and time in arthritic mice significantly increased compared to nonarthritic animals. Treatment with BoNT/A in the arthritic limb decreased this offloading; however, statistical analysis only showed significance in weightbearing. Conclusion: IA Col monoarthritis increased evoked and spontaneous pain behaviors in female mice after four weeks. Treatment with IA BoNT/A decreased pain behaviors but only forelimb weight bearing showed a significant improvement. This led us to conclude that treatment with BoNT/A is not an effective analgesic for the treatment of chronic degenerative knee arthritis in murine models.",

keywords = "Botox{\texttrademark}, Mouse, Neurotoxins, Osteoarthritis, Pain",

author = "Nicole Blanshan and Mahowald, {Maren L.} and Christopher Dorman and Sandra Frizelle and Krug, {Hollis E.}",

note = "Funding Information: This work was supported by Merit Review Award #RX000379-05 from the US Department of Veterans Affairs Rehabilitation Research and Development Service . The contents do not represent the views of the US department of Veterans Affairs or the United States Government. Publisher Copyright: {\textcopyright} 2018 The Authors",

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doi = "10.1016/j.toxicon.2018.11.307",

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AU - Mahowald, Maren L.

AU - Dorman, Christopher

AU - Frizelle, Sandra

AU - Krug, Hollis E.

N1 - Funding Information: This work was supported by Merit Review Award #RX000379-05 from the US Department of Veterans Affairs Rehabilitation Research and Development Service . The contents do not represent the views of the US department of Veterans Affairs or the United States Government. Publisher Copyright: © 2018 The Authors

PY - 2019/2

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N2 - Purpose: We previously reported the efficacy of intraarticular (IA) rimabotulinumtoxinB (BoNT/B) in a murine model of chronic degenerative arthritis pain. This study aimed to measure the analgesic effects of onabotulinumtoxinA (BoNT/A) on collagenase induced chronic degenerative arthritis joint pain. Methods: Chronic degenerative arthritis was produced by IA injection of 10 μl collagenase (Col) (10 IU) into the left knee of C57BL/6J female mice 4 weeks prior to pain assessment. IA BoNT/A was injected 3 days before testing. Arthritis pain was measured as evoked pain scores (EPS) and spontaneous pain behaviors with an advanced dynamic weight bearing (ADWB) device. EPS was a tally of fights and vocalizations exhibited in one minute with knee palpation. Percent body weight and percent time spent on each limb was quantified. All mice were 12 weeks old at the time of examination. Results: IA Col increased EPS and reduced ADWB measures of percent weight bearing on the left hind limb compared to naïve mice. BoNT/A treatment reduced EPS and increased weight bearing on the left hind limb. The improvements were not significant compared to the Col group. There was no significant difference in time spent on the left hind limb between any treatment groups. Forelimb ADWB measures of percent weight and time in arthritic mice significantly increased compared to nonarthritic animals. Treatment with BoNT/A in the arthritic limb decreased this offloading; however, statistical analysis only showed significance in weightbearing. Conclusion: IA Col monoarthritis increased evoked and spontaneous pain behaviors in female mice after four weeks. Treatment with IA BoNT/A decreased pain behaviors but only forelimb weight bearing showed a significant improvement. This led us to conclude that treatment with BoNT/A is not an effective analgesic for the treatment of chronic degenerative knee arthritis in murine models.

AB - Purpose: We previously reported the efficacy of intraarticular (IA) rimabotulinumtoxinB (BoNT/B) in a murine model of chronic degenerative arthritis pain. This study aimed to measure the analgesic effects of onabotulinumtoxinA (BoNT/A) on collagenase induced chronic degenerative arthritis joint pain. Methods: Chronic degenerative arthritis was produced by IA injection of 10 μl collagenase (Col) (10 IU) into the left knee of C57BL/6J female mice 4 weeks prior to pain assessment. IA BoNT/A was injected 3 days before testing. Arthritis pain was measured as evoked pain scores (EPS) and spontaneous pain behaviors with an advanced dynamic weight bearing (ADWB) device. EPS was a tally of fights and vocalizations exhibited in one minute with knee palpation. Percent body weight and percent time spent on each limb was quantified. All mice were 12 weeks old at the time of examination. Results: IA Col increased EPS and reduced ADWB measures of percent weight bearing on the left hind limb compared to naïve mice. BoNT/A treatment reduced EPS and increased weight bearing on the left hind limb. The improvements were not significant compared to the Col group. There was no significant difference in time spent on the left hind limb between any treatment groups. Forelimb ADWB measures of percent weight and time in arthritic mice significantly increased compared to nonarthritic animals. Treatment with BoNT/A in the arthritic limb decreased this offloading; however, statistical analysis only showed significance in weightbearing. Conclusion: IA Col monoarthritis increased evoked and spontaneous pain behaviors in female mice after four weeks. Treatment with IA BoNT/A decreased pain behaviors but only forelimb weight bearing showed a significant improvement. This led us to conclude that treatment with BoNT/A is not an effective analgesic for the treatment of chronic degenerative knee arthritis in murine models.

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KW - Pain

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The analgesic effect of intraarticular OnabotulinumtoxinA in a female murine model of collagenase induced chronic degenerative monoarthritis

Abstract

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