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

Preclinical pilot study.

To explore peripheral and central nociceptive mechanisms that contribute to muscle stretch-induced locomotor deficits following spinal cord injury.

Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA.

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.

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.

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.