The influence of muscle relaxers on physiologic processes and exercise
Original Editor - Stacie Price
- 1 Introduction
- 2 Botulinum Toxin Type-A & Botulinum Toxin
- 3 Diazepam
- 4 Baclofen
- 5 Risk of Injury
- 6 Recent Related Research (from Pubmed)
- 7 References
It is important to understand the effects muscle relaxers have on the physiological processes of the body because as therapists it is likely some patients will be using these drugs. Muscle relaxers are commonly used to decrease muscle spasticity or spasms and lessen low back pain from musculoskeletal diseases or injuries . Muscle relaxers are a class of drug that effectively decreases skeletal muscle function which in turn produces a tranquilizing effect. Common types of muscle relaxers include:
• Baclofen (Lioresal, Baclosan)
• Cyclobenzaprine (Flexeril)
• Metaxalone (Skelaxin)
• Carisoprodol (Soma, Carisoma, Sodol)
• Methocarbamol (Marbaxin, Robaxin)
• Chlorzoxazone (Parafon Forte, Remular)
• Orphenadrine (Flexon, Norgesic, Norflex)
• Dantrolene (Dantrium)
• Tizanidine (Zanaflex) 
• Botulinum toxin type-A
Botulinum Toxin Type-A & Botulinum Toxin
Increased Muscle Function and Strength in Combination with Strength Training:
Botulinum toxin type-A (BoNT-A) is one type of muscle relaxer that could be commonly seen within a rehabilitation type setting. Research has shown that BoNT-A injections can produce positive outcomes when it comes to controlling spasticity and muscle tone. When considering the effects of exercise and BoNT-A, children who have cerebral palsy (CP) are a good target population to consider given the spasticity that often accompanies the disease. Research has shown that children who receive BoNT-A injections and strength training programs show both an increase in muscle volume as well as a rise in strength . The timing of the injections in relation to strength training did not seem to be a factor in strength improvement, and overall children with CP who received this injection had positive outcomes in their functional ability . This is clinically significant because therapists will be able to increase strength in areas that may be contracted with the assistance of BoNT-A injections.
Loss of Strength and Function without Proper Exercise:
Another Study looked at the effects of BoNT-A injections for treating spasticity in individuals who had suffered a stroke. As one could imagine, spasticity in the lower extremities can have detrimental effects on an individual’s ability to walk, and this can directly influence their ability to ambulate and gain back independence in life. Many individuals who have been affected by a stroke will have BoNT-A injections to reduce spasticity, but do not include therapeutic activities to either increase strength or function . The results of this study show that those who receive BoNT-A injections and a self-rehabilitation program improve their maximal gait speed, distance covered and max speed during 6MWT-modifeid (6 minute walk test), and time taken to go up or down a flight of stairs in comparison to those who only receive the injections . This research shows that a home stretching and strengthening program can help prevent muscle wasting, and can also improve gait patterns which will then increase an individual's ability to move around independently.
Decrease in Acetylcholine Production:
Botulinum toxin, after being purified from botulism, also works as a muscle relaxer. It attaches to presynaptic terminal membranes in the skeletomuscular junction. After binding, it destroys proteins that help to make acetylcholine. When it is injected into a specific muscle, the muscle is less excitable, due to the smaller amount of acetylcholine. This allows the muscle to relax. It can also be used to help someone dress better, wash their hands, and other activities of daily living that use extension in the wrist, elbows, and fingers.
Adverse Effects of Botulinum Toxin:
Like many other muscle relaxers, using botulinum can have adverse effects. Long term use inhibits the release of acetylcholine. A decrease in acetylcholine levels causes the muscle to relax, but a lack of acetylcholine paralyzes the muscle fibers. The paralysis in those muscle fibers can spread, and cause loss of function in the muscle.
Diazepam works by inhibiting the excitability of the central nervous system, or CNS. This happens when Diazepam binds to receptors at GABA synapses and boost the GABA inhibiting effects. This mechanism allows Diazepam to act as a muscle relaxer, and increases the GABA effect on alpha motor neuron activity in the spinal cord. 
Improved Healing Following Musculoskeletal Injury:
One side effect of this drug is relaxation of the skeletal muscle, which will lead to sedation and less general motor activity. This can help someone who is recovering from a musculoskeletal injury. The sedation leads the patient to rest, which will lead to better healing during the initial time after the injury.
Negative Effects of Diazepam:
There are also negative side effects associated with Diazepam. If a patient continues to use this drug, they can become addicted. Withdrawal symptoms can include seizures, anxiety, agitation, tachycardia, and sometimes death. This drug is best used for short-term relief for an injury.
Baclofen is a muscle relaxer used in the generalized treatment for patients with severe spasticity. It acts as an agonist to the gamma-aminobutyric acid, type B (GABA-B) receptor. GABA-B is an inhibitory neurotransmitter receptor, so Baclofen functions in this same manner as it attaches to it, resulting in the reduction of muscle contractions (and, therefore, reduces muscle spasms) . Baclofen can be administered as an oral treatment or via an intrathecal baclofen (ITB) pump. The pump is implanted in the abdomen with a catheter that inserts into the spine’s subarachnoid space to directly release the baclofen into the cerebrospinal fluid . Dosage depends on severity of spasticity, as well as patient tolerance. The use of baclofen as a treatment for spasticity can promote improved gait mobility, activities of daily living, while reducing pain. However, if a therapist is to suggest this potential treatment, she should be aware of the adverse reactions to this muscle relaxant that will be explained in further detail below.
Improvements in Physical Function:
Physical therapists may encounter patients suffering from moderate to severe spasticity caused by spinal cord injuries, hereditary spastic paraplegia (HSP), acquired brain injuries, or cerebral palsy to name a few. Certain cases may require the use of pharmacological interventions coupled with intense rehabilitation in order to produce optimal neuromuscular results to improve physical function. Baclofen is a muscle relaxant often used to treat generalized spasticity by reducing muscle spasms. One study reported positive assessments in gait mobility in patients with HSP after intrathecal baclofen (ITB) treatments . It was noted that patients had better results with the treatment when they adhered to a rehabilitation intervention plan, making it imperative that therapists motivate a patient to follow their prescribed program . Improvements were seen by McIntyre et al. (2014), in studies involving patients with chronic spinal cord injuries . A few studies reported positive progressions in activities of daily living and functional improvements in physical activities such as stair climbing and transfers . In a study done by physical therapists involving a single patient post-stroke, the patient’s goals of short hikes and attending the theater without a wheelchair were met with the use of baclofen, BoNT-A and high adherence to a rehabilitation program . These progressions give patients more independence because the reduced spasticity allows for better muscular control and therapy can help strengthen and re-educate. It is important for physical therapists to recognize these benefits when coupling a rehabilitation program with pharmacological interventions; however, if a therapist is to recommend baclofen, she must also be aware of potential adverse reactions.
Interruption of Nueroplastic Changes that Improve Motor Performance:
In patients without complications like stroke or a traumatic brain injury, drugs such as Diazepam and Baclofen can interfere with normal neuron changes that help improve motor activities. Lundbye-Jensen, J., Neilsen, J. B., Peterson, T. H., & Willerslev-Olsen, M. (2011) studied healthy patients learning a visuomotor skill. They taught the skill to 16 healthy subjects and used the primary motor cortex leg area in the brain to create responses in the anterior tibialis muscle. The authors found that Diazepam and Baclofen interrupt some of the neuroplastic changes that help patients improve their motor performance. Physiotherapists should use these medications with much caution, especially in healthy subjects. 
Other complications to consider when taking intrathecal baclofen are instances of infection, seizures, and withdrawal due to the use of an intrathecal baclofen pump. According to a study by Zdolsex, H. A., Olesch, C., Antolovich, G., & Reddihough, D. (2011), researchers identified eight problems, two obstacles, and seven true complications associated with intrathecal baclofen use in a group of eighteen patients who were receiveing intrathecal baclofen treatment. The three categories were defined as follows:
"Problems were defined as difficulties that did not require surgical intervention and fully resolved before the end of treatment. Obstacles were defined as difficulties that required surgical intervention but that were fully resolved before the end of treatment. True complications were intra-and postoperative problems not fully resolved before the end of treatment."
These complications ranged from infection, depression, catheter malfunctions, and withdrawal symptoms.  Exercise professionals should be aware of these complications associated with intrathecal baclofen when creating exercise plans for patients who may be taking this medication.
In another study, researchers observed ninety nine patients with multiple sclerosis who were being treated with intrathecal baclofen. These subjects were being observed for the prevalence of seizures while taking intrathecal baclofen. Seven patients reported having seizures during the study. Each seizure was related to an overdose of intrathecal baclofen due to a malfunction in the pump.  In a case report of a forty one year old woman with multiple sclerosis, epileptic seizures were observed after the woman started taking intrathecal baclofen. Researchers found that the baclofen was having a negative reaction with the woman's medication for a psychotic disorder.  Seizures are another complication to be considered related to intrathecal baclofen. In each instance, the seizures seemed to occur as a reaction to other factors.
The final complication related to intrathecal baclofen pumps is the threat of withdrawal. This complication is similar to the possibility of overdose because it is related to a malfunction in the pump itself. In a study of eighty eight patients who were using SynchroMed pumps to administer their medication, twenty one patients experienced withdrawal from their medication. The patients who were taking intrathecal baclofen experienced withdrawal symptoms such as "pruritus without rash, generalized paresthesias, and sudden increased spasticity."  While this complication can be very dangerous, it can be avoided. It is important to ensure that the pump and catheter are working properly, and that the patients are not taking any other medications that may react poorly with the muscle relaxant.
Children with Cerebral Palsy:
Some successful cases of intrathecal baclofen treatment have also been reported. In one study in particular, the authors specifically focused on children with cerebral palsy. This systematic review actually suggested intrathecal baclofen over taking it orally because the baclofen pump controls the amount the child is receiving, rather than forcing them to physically take medicine each day. The aim of the study was to determine the effectiveness of intrathecal baclofen treatment on gross motor function, ease of care, and overall quality of life for children with cerebral palsy. At the end of the study, it was determined that it does cause improvements on motor function and quality of life by helping the child relax and by easing muscle contractions.  This article shows that there are some positive effects of intrathecal baclofen as well, and therapists should use further research and judgement to determine its usefulness.
Risk of Injury
Skeletal muscle relaxants can produce effects in the central nervous system and are often associated with the symptoms of drowsiness and dizziness. Patients in the age group of 60 and over taking skeletal muscle relaxants are more likely to experience injuries than the same age group of people not taking them. Common injuries suffered were fractures, contusions, falls, and lacerations. Patients 60 years and older accounted for 16% of skeletal muscle relaxant consumers. While skeletal muscle relaxants can be beneficial for some conditions, they can produce negative side effects especially in the elderly population. Before working with a patient, the therapist should determine whether the patient is using muscle relaxants. If the patient is using them, the therapist should be prepared to monitor the patient accordingly and be prepared to assist the patient in order to keep them safe.
Recent Related Research (from Pubmed)
- United States National Library of Medicine. Muscle Relaxants. http://livertox.nih.gov/MuscleRelaxants.htm (accessed 2 December 2015).
- Williams SA, Elliott C, Valentine J, Gubbay A, Shipman P, Reid S. Combining strength training and botulinum neurotoxin intervention in children with cerebral palsy: The impact on muscle morphology and strength. Disability and rehabilitation. 2013 Apr;35(7):596-605.
- Roche N, Zory R, Sauthier A, Bonnyaud C, Pradon D, Bensmail D. Effect of rehabilitation and botulinum toxin injection on gait in chronic stroke patients: A randomized controlled study. Journal of rehabilitation medicine. 2015 Jan;47(1):31-7.
- Ciccone, Charles D. Pharmacology in Rehabilitation: Contemporary perspectives in rehabilitation. F.A. Davis. 2015; 180-182
- McIntyre A, Mays R, Mehta S, Janzen S, Townson A, Hsieh J, Wolfe D, Teasell R. Examining the effectivenss of intrathecal baclofen on spasticity in individuals with chronic spinal cord injury: A systematic review. The Journal of Spinal Cord Medicine. 2014;37(1):11-8. DOI: 10.1179/2045772313Y.0000000102
- Heetla HW, Staal MJ, Proost JH, van Laar T. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy. 2014 Nov;95(11):2199-206. doi: 10.1016/j.apmr.2014.04.030
- Margetis, K, Korfias, S, Boutos, N, Gatzonis, S, Themistocleous, M, Siatouni, A, Dalivigka, Z, Flaskas, T, Stranjalis, G, Boviatsis, E, Sakas, D. Intrathecal baclofen therapy for the symptomatic treatment of hereditary spastic paraplegia. Clinical Neurology and Neurosurgery. 2014;123:142-5. http://dx.doi.org/10.1016/j.clineuro.2014.05.024
- Barakatt, E, Coleman-Salgado, B, McKeough, M, Mandeville, D, Gong, J, Mintz, E, Thatch, J, Vourakis, A, Thakur, N. Mobility and gait outcomes following intensive rehabilitation, onabotulinumtoxin A, and baclofen treatment chronic post-stroke. Journal of Allied Health. 2014;43(4):229-34.
- Lundbye-Jensen J, Neilsen JB, Peterson TH, Willerslev-Olsen, M. The effect of baclofen and diazepam on motor skill acquisition in healthy subjects. Exp Brain Res 2011; 213(4), 465-474 DOI:10.1007/s00221-011-2798-5
- Zdolsek HA, Olesch C, Antolovich G, Reddihough D. Intrathecal baclofen therapy: Benefits and complications. Journal of Intellectual Developmental Disability 2011;36:207-13.
- Schuele SU, Kellinghaus C, Shook SJ, Boulis N, Bethoux FA, Loddenkemper T. Incidence of seizures in patients with multiple sclerosis treated with intrathecal baclofen. Neurology 2015;64:1086-87.
- D'Aleo G, Rifici C, Kofler M, Sessa E, Saltuari L, Bramanti P. Seizure after intrathecal baclofen bolus in multiple sclerosis patient treated with oxcarbazepine. Neurological Science 2011;32:293-95.
- Taha J, Favre J, Janszen M, Galarza M, Taha A. Correlation between withdrawal symptoms and medication pump residual volume in patients with implantable SynchroMed pumps. Neurosurgery 2004;55:390-94.
- Hasnat MJ, Rice JE, O'Donnell ME. Intrathecal baclofen for treating spasticity in children with cerebral palsy. The Cochrane Library 2015; (11). 10.1002/14651858.CD004552.pub2.
- Spence MM, Shin PJ, Lee EA, Gibbs NE. Risk of injury associated with skeletal muscle relaxant use in older adults. The Annals of Pharmacology 2013; 47(7-8), 993-998. doi: 10.1345/aph.1R735