Baclofen or nNOS inhibitor affect molecular and behavioral alterations evoked by traumatic spinal cord injury in rat spinal cord

• Published in: The spine journal Vol. 15; no. 6; pp. 1366 - 1378
• Main Authors: Kisucká, Alexandra, PhD, Hricová, Ľudmila, PhD, Pavel, Jaroslav, PhD, Strosznajder, Joanna B., PhD, Chalimoniuk, Malgorzata, PhD, Langfort, Jozef, PhD, Gálik, Ján, PhD, Maršala, Martin, MD, Radoňak, Jozef, PhD, Lukáčová, Nadežda, DSc
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2015
• Subjects: Animals; Baclofen; Baclofen - pharmacology; Enzyme Inhibitors - pharmacology; GABA-B Receptor Agonists - pharmacology; Hot Temperature; Male; Motor Neurons - drug effects; Motor Neurons - metabolism; Neuronal nitric oxide synthase; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - metabolism; NNLA; Orthopedics; Pain Perception - drug effects; Pain Perception - physiology; Rat; Rats; Rats, Wistar; Reaction Time - drug effects; Reaction Time - physiology; Reflex - drug effects; Reflex - physiology; Reflex response; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Spinal cord injury; Tail-flick text; α-Motoneurons; NNLA; Neuronal nitric oxide synthase; Rat; Baclofen; Spinal cord injury; Tail-flick text; Reflex response; α-Motoneurons
• ISSN: 1529-9430; 1878-1632
• DOI: 10.1016/j.spinee.2014.08.013

Abstract Background context The loss of descending control after spinal cord injury (SCI) and incessant stimulation of Ia monosynaptic pathway, carrying proprioceptive impulses from the muscles and tendons into the spinal cord, evoke exaggerated α-motoneuron activity leading to increased reflex response. Previous results from our laboratory have shown that Ia monosynaptic pathway is nitrergic. Purpose The aim of this study was to find out whether nitric oxide produced by neuronal nitric oxide synthase (nNOS) plays a role in setting the excitability of α-motoneurons after thoracic spinal cord transection. Study design We tested the hypothesis that the inhibition of nNOS in α-motoneurons after SCI could have a neuroprotective effect on reflex response. Methods Rats underwent spinal cord transection at Th10 level followed by 7, 10, and 14 days of survival. The animals were treated with Baclofen (a gamma aminobutyric acid B receptor agonist, 3 μg/two times per day/intrathecally) applied for 3 days from the seventh day after transection; N -nitro- l -arginine (NNLA) (nNOS blocator) applied for the first 3 days after injury (20 mg/kg per day, intramuscularly); NNLA and Baclofen; or NNLA (60 mg/kg/day, single dose) applied on the 10th day after transection. We detected the changes in the level of nNOS protein, nNOS messenger RNA, and nNOS immunoreactivity. To investigate the reflex response to heat-induced stimulus, tail-flick test was monitored in treated animals up to 16 days after SCI. Results Our data indicate that Baclofen therapy is more effective than the combined treatment with NNLA and Baclofen therapy. The single dose of NNLA (60 mg/kg) applied on the 10th day after SCI or Baclofen therapy reduced nNOS expression in α-motoneurons and suppressed symptoms of increased reflex activity. Conclusions The results clearly show that increased nNOS expression in α-motoneurons after SCI may be pharmacologically modifiable with Baclofen or bolus dose of nNOS blocker.