Muscle pain is most frequently related to tension, overuse, or muscle injury from exercise or physically-demanding work. In these situations, the pain tends to involve specific muscles and starts during or just after the activity. It is usually obvious which activity is causing the pain.
Muscle pain also can be a sign of conditions affecting your whole body, like some infections (including the flu) and disorders that affect connective tissues throughout the body (such as lupus). One common cause of muscle aches and pain is fibromyalgia, a condition that includes tenderness in your muscles and surrounding soft tissue, sleep difficulties, fatigue, and headaches.
Because of the enhancement of inhibition in the CNS, most spasmolytic agents have the side-effects of sedation, drowsiness and may cause dependence with long term use. Several of these agents also have abuse potential, and their prescription is strictly controlled.
The benzodiazepines, such as diazepam, interact with the GABAA receptor in the central nervous system. While it can be used in patients with muscle spasm of almost any origin, it produces sedation in most individuals at the doses required to reduce muscle tone.
Baclofen is considered to be at least as effective as diazepam in reducing spasticity, and causes much less sedation. It acts as a GABA agonist at GABAB receptors in the brain and spinal cord, resulting in hyperpolarization of neurons expressing this receptor, most likely due to increased potassium ion conductance. Baclofen also inhibits neural function presynaptically, by reducing calcium ion influx, and thereby reducing the release of excitatory neurotransmitters in both the brain and spinal cord. It may also reduce pain in patients by inhibiting the release of substance P in the spinal cord as well.
Clonidine and other imidazoline compounds have also been shown to reduce muscle spasms by their central nervous system activity. Tizanidine is perhaps the most thoroughly studied clonidine analog, and is an agonist at α2-adrenergic receptors, but reduces spasticity at doses that result in significantly less hypotension than clonidine. Neurophysiologic studies show that it depresses excitatory feedback from muscles that would normally increase muscle tone, therefore minimizing spasticity. Furthermore, several clinical trials indicate that tizanidine has a similar efficacy to other spasmolytic agents, such as diazepam and baclofen, with a different spectrum of adverse effects.
The hydantoin-derivative dantrolene is a spasmolytic agent with a unique mechanism of action outside of the CNS. Dantrolene reduces skeletal muscle strength by inhibiting the excitation-contraction coupling in the muscle fiber. In normal muscle contraction, calcium is released from the sarcoplasmic reticulum through the ryanodine receptor channel, which causes the tension-generating interaction of actin and myosin. Dantrolene interferes with the release of calcium by binding to the ryanodine receptor and blocking the endogenous ligand ryanodine by competitive inhibition. Muscle that contracts more rapidly is more sensitive to dantrolene than muscle that contracts slowly, although cardiac muscle and smooth muscle are depressed only slightly, most likely because the release of calcium by their sarcoplasmic reticulum involves a slightly different process. Major adverse effects of dantrolene include general muscle weakness, sedation, and occasionally hepatitis.
Other common spasmolytic agents include: methocarbamol, carisoprodol, chlorzoxazone, cyclobenzaprine, gabapentin, metaxalone, and orphenadrine.
Muscle Relaxant Clinical use
Spasmolytics like carisoprodol, cyclobenzaprine, metaxalone, and methocarbamol are commonly prescribed for low back pain or neck pain, fibromyalgia, tension headaches and myofascial pain syndrome. However, they are not recommended as first-line agents; in acute low back pain, they are not more effective than paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs), and in fibromyalgia they are not more effective than antidepressants. Nevertheless, there is some (low quality) evidence suggesting that muscle relaxants can add benefit to treatment with NSAIDs. In general, there is no high quality evidence to support their use. No drug has been shown to be better than another, and all of them have adverse effects, particularly dizziness and drowsiness. Concerns about possible abuse and interaction with other drugs, especially if increased sedation is a risk, further limit their use. A muscle relaxant is chosen based on its adverse-effect profile, tolerability, and cost.
Agents like dantrolene and baclofen are not advised for orthopedic conditions, but rather for neurological conditions such as spasticity in cerebral palsy and multiple sclerosis. Dantrolene, although thought of primarily as a peripherally acting agent, is associated with CNS effects, whereas baclofen activity is strictly associated with the CNS.
Muscle relaxants are thought to be useful in painful disorders based on the theory that pain induces spasm and spasm causes pain. However, there is considerable evidence to contradict this theory.
In general, muscle relaxers are not approved by FDA for long term use. However, rheumatologists often prescribe Flexeril nightly on a daily basis in order to increase stage 4 sleep. By increasing this sleep stage patients feel more refreshed in the morning. Improving sleep is also beneficial for patients who have fibromyalgia.
Muscle relaxants such as tizanidine are prescribed in the treatment of tension headaches. Diazepam and carisoprodol are not recommended for older adults, pregnant women, or people who suffer depression or for those with a history of drug or alcohol addiction.
Non-depolarising muscle relaxants are commonly used during anaesthesia to provide relaxation for surgery, to allow mechanical ventilation and they are also regularly used in intensive care. This article describes the mechanisms by which the drugs work and also the differences between specific drugs.
Non-depolarising muscle relaxant Mechanism of action
Non-depolarising muscle relaxant drugs (NDMRD) compete with acetyl choline (ACh) molecules released at the neuromuscular junction to bind with the ACh receptors on the post synaptic membrane of the motor endplate. They therefore block the action of ACh and prevent depolarisation (or activation) of the muscle contraction process. Muscle groups differ in their sensitivity to muscle relaxants; ocular muscles responsible for opening and moving the eyes are the most sensitive followed by the muscles of the jaw, neck, limbs, intercostals and abdomen. The diaphragm is the least sensitive muscle, which is why patients undergoing surgery sometimes hiccup or breathe as an early sign that the relaxants are wearing off.
Non-depolarising muscle relaxant drugs also act on presynaptic receptors interfering with the entry of calcium which causes an inhibition in the release of ACh. Other drugs such as the aminoglycoside antibiotics (eg gentamicin) and volatile agents may also effect this mechanism and increase sensitivity to relaxants.
A variety of relaxant drugs are in use in different parts of the world. All produce profound muscle paralysis but have varying effects on the autonomic nervous system. None of the drugs cross the blood brain barrier as they are water soluble, polar molecules and therefore have no effect on the central nervous system. All non depolarising drugs should be used with care in patients suspected to be suffering with myasthenia gravis or myasthenic syndrome as patients with these conditions are extremely sensitive to their effects.
