Combining clinically common drugs with hindlimb stretching in spinal cord injured rodents

Combining clinically common drugs with hindlimb stretching in spinal cord injured rodents

Study design Preclinical pilot study. Objectives To explore peripheral and central nociceptive mechanisms that contribute to muscle stretch-induced locomotor deficits following spinal cord injury. Setting Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA. Methods Ten female Sprague-Da...

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Bibliographic Details
Published in:Spinal cord Vol. 62; no. 10; pp. 574 - 583
Main Authors: Forston, Morgan J., Jordan, Savannah L., Cesarz, Greta M., Burke, Darlene A., Shum-Siu, Alice, Petruska, Jeffrey C., Magnuson, David S. K.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-10-2024
Nature Publishing Group
Subjects:
14/63
631/378/1959/2605
631/378/2632/1823
Acetaminophen
Analgesics
Anatomy
Baclofen
Biomedical and Life Sciences
Biomedicine
Drug development
Drugs
Human Physiology
Ibuprofen
Injuries
Injury prevention
Limbs
Morphine
Muscles
Neurochemistry
Neuropsychology
Neurosciences
Nonsteroidal anti-inflammatory drugs
Pain perception
Recovery
Research facilities
Spasticity
Spinal cord injuries
Stretching
Vibrations
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Summary:Study design Preclinical pilot study. Objectives To explore peripheral and central nociceptive mechanisms that contribute to muscle stretch-induced locomotor deficits following spinal cord injury. Setting Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA. Methods Ten female Sprague-Dawley rats received moderate, 25 g/cm T10 contusion injuries and recovered for 4 weeks. Rats were divided into three groups: Morphine/Ibuprofen-treated, Acetaminophen/Baclofen-treated, and saline control. Each group received daily hindlimb muscle stretching during weeks 4, 5, 9, and 10 post-injury and drugs were administered with stretching during weeks 4 and 9 only. Locomotor function was assessed throughout the experiment using the BBB Open Field Locomotor Scale. Hindlimb responses including spasticity, writhing, and clonic-like vibrations during muscle stretching were classified and scored. Results Consistent with our previous studies, hindlimb muscle stretching caused significant deficits in locomotor recovery following spinal cord injury. Baclofen and Ibuprofen partially mitigated the stretching effect, but none of the drugs significantly prevented the drop in locomotor function during stretching. Interestingly, treatment with Baclofen or Ibuprofen significantly reduced hindlimb responses such as spasticity and writhing during stretching, while Morphine exacerbated clonic-like vibrations in response to stretching maneuvers. Conclusions These findings suggest that stretching may inhibit locomotor recovery through combined mechanisms of peripheral inflammation and sensitization of nociceptive afferents. When combined with central sprouting and loss of descending controls after SCI, this results in exaggerated nociceptive input during stretching. The inability of the applied clinical drugs to mitigate the detrimental effects of stretching highlights the complexity of the stretching phenomenon and emphasizes the need for further investigation.
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ISSN:1362-4393
1476-5624
1476-5624
DOI:10.1038/s41393-024-01023-3