Effects of Baclofen on Presynaptic Inhibition in Humans

This study examines the role of the GABA-B receptor in long-lasting presynaptic inhibition of primary afferents in human participants. Participants will come in for two visits, receiving baclofen (a GABA-B receptor agonist) on one visit and a placebo during the other. Electro-physiological measures will be use during both visit to asses presynaptic inhibition.

The ability to execute purposeful movements relies on sensory information coming from the body. This sensory information tells us where are limbs are in relation to the rest of our body (posture sense), how fast they are moving (kinesthetic sense), how forcefully we are making a contraction (muscular sense) and if we are being contacted by external objects, changes in temperature, pain, etc (somatic sense). Without these senses, the investigators could not make well-controlled movements or navigate in our environment safely. Because of the importance of these sensory inputs, the nervous system has designed a highly regulated system to control the amount and quality of sensory inflow entering into both the spinal cord and brain. The investigators wish to re-investigate how sensory pathways from our body controls the inflow of sensory inputs in adults with and without neurological injury. Specifically, the investigators want to test if the long-lasting suppression of sensory inflow by other sensory nerves is regulated by GABA-B receptors. The investigators will test this by giving participants the GABA-B receptor agonist baclofen. Nerve stimulation and muscle responses will be used to understand how sensory transmission is being controlled in the spinal cord and the GABA-B receptors involvement. Results from these studies will provide important fundamental information about how normal sensory inflow is controlled so that the investigators can better understand how it may be altered after injury to the brain and spinal cord. This information will open new avenues of study into the treatment of sensory-related dysfunction such as spasticity and motor incoordination that occurs after central nervous system injury or disease.

This is a double blinded, cross-over, retrospective cohort design where the size of the H-reflex and motor unit firing rates will be examined before and after oral intake of baclofen or placebo.

Control participants will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other.

Participants with a spinal cord injury will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other.

Participants will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other. During each visit the soleus H-reflex will be measured and conditioned by common peroneal nerve stimulation to assess presynaptic inhibition.

Our primary objective is to determine how activation of GABA-B receptors control transmission of sensory afferents as measured by the H-reflex.

Inclusion Criteria: Healthy adults between the ages of 18 and 65 years. General good health Exclusion Criteria: Contraindications to baclofen such as a known hypersensitivity to baclofen, renal impairment, stroke, epilepsy, pregnancy and lactation. Injury to peripheral nerves or muscles. Injury to nerves or muscles will confound the interpretation of the spinal reflex data. Participants with spinal cord injury already taking oral baclofen to manage spasticity.

De-identified individual participant data will be available to other researchers upon that researchers request.

IPD will be provided to researchers who have contacted the primary investigator and requested additional data. All data will be de-identified.