Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disease of the central nervous system characterized by progressive degeneration of the corticospinal tract and anterior horn motor neurons in the motor cortex, brainstem and spinal cord of the patient’s brain, mainly manifesting as lesions of the upper and lower motor neurons, which can lead to a series of typical clinical symptoms: muscle weakness and atrophy, spasticity and tonicity, speech disorders, increased oral secretions, dysphagia and fatal respiratory failure. In addition, there are a number of atypical symptoms, directly or indirectly related to the above symptoms, which seriously affect the quality of life of patients, especially the high percentage of pain onset and the most obvious impact on patients. The literature reports that nearly 70% of ALS patients experience pain at different stages of the disease course, and the frequency of occurrence seems to be positively correlated with disease progression. However, despite this prevalence, research on pain in ALS patients is scarce and lacks systematicity, and there are no randomized controlled drug clinical trials addressing pain in ALS, so guidance on pain in ALS patients in various ALS guidelines and consensus is usually scattered in the management of various comorbidities and not centrally addressed. Thus, helping patients to reduce pain should be considered as an important aspect of fine ALS care. In this paper, we try to briefly analyze the types, causes and countermeasures of ALS-associated pain, taking into account the available information and the actual patients.
I. Types and causes of ALS-related pain
ALS patients often experience pain mainly involving muscle cramps, spasms (tonicity), skeletal muscle pain, joint problems and possible skin pain.
1. Muscle cramps (painful spasms, cramps)
A muscle cramp is a sudden involuntary muscle contraction that can occur anywhere and cause severe pain. These contractions may vary greatly in intensity and frequency, but tend to occur frequently early in the course of the disease, especially when exerting force, such as sneezing, which triggers abdominal muscle cramps. Although many patients present with this symptom several months before the onset of muscle weakness, it is often after the diagnosis that it is really noticed. As a result, this is an often overlooked feature of ALS. Muscle cramps can be exacerbated by cold stimulation or poor circulation (holding a position for a long time). However, it will gradually decrease over time because as the disease progresses, the nerve cells lose their ability to stimulate muscle contraction.
2. Spasticity (tonicity)
Spasticity (tonicity) is another common feature of ALS and is a manifestation of high muscle tone and active tendon reflexes. The hyperactive tendon reflexes associated with spasticity are caused by abnormal spinal cord signal input, and this imbalance between spinal cord inhibition and excitatory (signal) input can also disrupt the nociceptive reflexes and cause flexor and extensor spasticity (tonicity). The spasm (tonicity) itself is not always painful, but it can trigger painful cramps that cause muscle fatigue or alter movement flexibility. In addition, there can be painful muscle contractures due to involuntary movement of stiff joints affecting the skeletal muscle system. All of these muscle activity-induced changes can substantially affect body posture, range of motion, and cause difficulty walking or coordinating activities, thus becoming a new source of pain.
3.Skeletal muscle pain
Both transient acute pain and persistent chronic pain in skeletal muscles have been reported in ALS. This pain is mainly the result of muscle immobility and may also be (combined with) joint inflammation. The frequent sites of occurrence mainly involve the back, legs, arms, shoulders and neck. Although the etiology of this pain is not well understood, it will be accompanied by progressive muscle atrophy and decreased muscle tone. This represents damage to bones, tendons, ligaments, joints, nerves, or the muscles themselves are affected. An imbalance in each of these intricate links can greatly affect muscle coordination, strength and function. This regression in coordination and strength and function can cause abnormal stress on ligaments, tendons and joints, which can cause microtrauma to the muscle tissue and trigger mild inflammation. As the disease progresses progressively, the above injuries and inflammation may recur, giving room for the onset of pain.
4. Joint problems
A high percentage of joint pain occurs in ALS patients. It is mainly caused by contracture due to inactivity, or aseptic arthritis induced in the joint area due to muscle weakness in an abnormal state (shoulder dislocation, foot drop). For example, shoulder condensation, which tends to occur after shoulder weakness, is the most common source of pain.
5. Skin pain
Patients with ALS also experience skin pain, which is mainly manifested as pressure sore pain and swollen limb pain. Among them, pressure sores, also known as decubitus ulcers, are soft tissue ulcers and necrosis caused by prolonged pressure on local tissues, impaired blood circulation, persistent local ischemia, hypoxia and malnutrition. They occur in areas with bony prominence, such as the sacrococcygeal area, sciatic tuberosity, greater trochanter of the femur, and the root of the foot, and are common in bedridden patients. In contrast, swelling of the limbs (lower extremities) in ALS patients without other combined organic pathologies (cardiogenic or nephrogenic diseases) is mainly due to limited limb movement, prolonged sitting position, and the inability of muscle atrophy to ensure effective blood return, forming a buildup and dilatation of the venous vessels, where water can penetrate into the surrounding tissues, causing swelling or edema. When this condition occurs repeatedly, the venous vessels become weaker and water is more easily lost to infiltration, leading to more severe swelling and a vicious cycle. Severe swelling can cause a painful burning sensation, and the skin becomes sensitive to changes in hot and cold temperatures. As circulation further deteriorates, the skin of the legs and feet becomes damaged and brittle.
In summary: Pain problems in ALS patients involve multiple systems throughout the body and the causes are often multifaceted. In addition to the effects of the disease itself, such as cramps and spasms, it is to a large extent caused by mobility problems, such as joint and skin problems. This also points us in the direction of pain relief and reduction.
Second, the response and management of ALS-related pain.
Since most of the ALS-related pain is caused to a large extent by immobility. Methods such as physical therapy, body extension and a certain range of (passive) movement exercises can be used in combination with pharmacotherapy to prevent contractures and reduce muscle cramps, spasms and pain. In patients with ALS, routine gentle resistance exercises can be used in conjunction with improving the static strength of the muscle groups and slowing their functional decline. Joint release techniques can also often maintain the elongation of affected muscle groups and are therefore effective in reducing skeletal muscle pain, cramps and spasms in ALS patients.
1. Treatment of muscle cramps
Levetiracetam showed effects in a small, non-blinded trial study (Class IV). Quinine sulfate has been banned by the FDA because of safety concerns. However, a recent Cochrane review of non-ALS cramps found that quinine sulfate was effective compared with placebo, while there were no differential serious adverse events. A randomized controlled trial of tetrahydrocannabinol did not show an effect for moderate to severe cramping in ALS patients (Class I). Other therapies such as massage, active exercise, hot bath hydrotherapy, carbamazepine, valium, phenytoin, and isoptin have been tested, but there are no controlled studies for ALS.
(1) Mild twitching can usually be relieved by stretching and staying well hydrated, or treated with vitamin E or magnesium.
(2) Levetiracetam can be tried, and if it is ineffective or has side effects, quinine sulfate (200 mg twice daily) may be effective (GCPP).
(3) Physical therapy, active exercise and/or hydrotherapy may be helpful
2. Treatment of spasticity (tonicity)
Physical therapy is the primary treatment for ALS spasticity (tonicity) and has been found to be effective (Class III). Although there are no trials in this area for ALS, other measures such as hydrotherapy, heat therapy, cryotherapy, ultrasound, electrical stimulation, chemical denervation and, rarely, surgical therapy are also used. In ALS patients with intractable spasticity states and associated pain, intrathecal baclofen is more effective than oral administration and can significantly improve patient quality of life (Class IV). Although not formally tested in patients with ALS, gabapentin (900-2400 mg daily), tizanidine (6C24 mg daily), memantine (10-60 mg daily), dantrolene (25-100 mg daily), tetrahydrozepam (100-200 mg daily), and valium (10-30 mg daily) have been used in clinical practice. type A Botulinum toxin has been successfully used to treat a case of clenching of teeth and wheezing.
(1) Conventional physical therapy is helpful for severe spasticity (tonicity).
(2) Anti-spasticity (tonicity) drugs such as baclofen and tizanidine can be tried.
(3) Intrathecal baclofen may be helpful if spasticity (tonicity) remains severe despite oral medication (GCPP).
(4) Hydrotherapy exercises at 32-34 degrees Celsius and cryotherapy may also be considered.
The following should be noted.
(1) For oral baclofen, usually 2 to 3 doses of 10 mg per day, which can be increased to 4 doses of 20 mg per day if a higher dose is necessary.
(2) Possible side effects of prescription drugs such as dantrolene sodium, tizanidine or gabapentin, including baclofen, include weakness, fatigue, drowsiness, etc. It is necessary to start with a small dose and increase it slowly, which can minimize the side effects. It is also important to note that these drugs should not be stopped suddenly.
(3) Excessive amounts of muscle relaxants such as baclofen can exacerbate muscle weakness and complicate the disease state.
(4) If stiffness is not well controlled by oral medications, the option of intrathecal baclofen pumps needs to be discussed with the physician. It is surgically implanted in the abdomen and administered directly into the cerebrospinal fluid through a small tube. Intrathecal administration allows for some avoidance of the adverse effects of baclofen, and the biggest benefit is that the dose can be changed in real time depending on the severity of the symptoms. Before intrathecal administration is considered, a lumbar puncture test is required to assess the degree of response to the drug.
3. Treatment of skeletal muscle pain
Without other organic lesions, general muscle pain can be treated with non-steroidal anti-inflammatory drugs such as ibuprofen or naproxen sodium. You can also try anti-anxiety depressants such as Celerity and Dextran. Dexedrine is fast-acting but should not be taken regularly; Celebrex can be taken regularly but is slow-acting. At first, you can take both Dexedrine, 2 times a day, one tablet, and Sellett, 1 time a day, 10mg (half a tablet); after 5 days, change to Sellett, 1 time a day, 20mg, and gradually stop taking Dexedrine.
4.Response measures for joint problems
The principle of coping with joint problems is to keep the limb in a functional position as much as possible to maintain the mobility of the joints, and at the same time to reduce the weight-bearing of the joints as much as possible, especially the shoulder, elbow, knee and ankle. Daily home-assisted stretching and (minor) mobility exercises can reduce or eliminate muscle stiffness and cramps, and also reduce the risk of developing joint contractures. Immobilization devices, standing frames, and ring neck braces (neck braces) can all be helpful. Recently, I have seen patients using aids such as foot drop orthoses and finger-splitting boards, which can be beneficial in relieving foot drop and finger contractures. For medications, intra-articular injections of non-steroidal anti-inflammatory drugs are available.
5.Management of skin pain
This article deals with skin pain mainly in terms of pressure sores and swelling.
Third, what needs to be added and emphasized
1.All the above treatments, especially the medication guidance, are for reference only. Because of the differences in patient conditions, it is important to communicate and discuss with a physician who understands the patient’s situation before treatment.
2, Narcotic analgesics, such as opioids, although historically the most effective drugs for intractable pain, are generally not recommended. Such drugs can inhibit breathing, reduce airway protection, inhibit coughing, impede bowel movements, and may also cause physical dependence, leading to further complications. If the patient is already in the terminal stage, in order to relieve pain and have to use, must seek medical guidance.
3, should avoid the use of skin patch type analgesics, because this way, drug absorption is very unstable also unpredictable.