Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder leading to impairments in limb movement, speaking, swallowing, and breathing. In a subset of patients with hereditary forms, frontotemporal dementia can occur, as well. There is no cure for ALS, and it is invariably a life-shortening illness. See Fast Facts # 73, 299–301, 411, and 437 for more information. Though central nervous system sensory areas are not typically implicated in ALS pathophysiology, pain is an often overlooked symptom. 1
Sources include primary disease-mediated pain such as spasticity, muscle cramping, and neuropathy, and secondary pain from reduced mobility. 2 There is a lack of robust data on the management of pain in ALS, including a near absence of clinical trial data. Therefore, much of the management advice outlined below is based on case studies, survey data, expert opinion, and clinical experience. Experts promote an interprofessional approach for optimal analgesic management.
Primary Disease-Mediated Pain
Spasticity
Spasticity is common, particularly in upper motor neuron (UMN)-predominant disease.
Nonpharmacological interventions: physical therapy (PT) and occupational therapy (OT) consultation for stretching and range of motion (RoM) exercises.3,4 PT/OT clinicians may supply neutral-position splinting of hands and feet as an analgesic tool. There is no data to suggest that endurance-based exercise regimens have benefit for spasticity.3,4
Skeletal muscle relaxants (SMRs): See Fast Fact #340. Baclofen and tizanidine are commonly prescribed. Dantrolene and benzodiazepines such as diazepam are utilized less frequently. There are no comparative trials of different SMRs for ALS-related spasticity. 3 Agent choice is often based on patient preference and a desire to minimize sedating side effects that can worsen mobility.
Botulinum toxin injection and intrathecal baclofen are typically avoided because their long-lasting effects can worsen weakness. They may be considered in slowly progressive ALS and/or severe spasticity (predominantly seen in primary lateral sclerosis, a form of ALS involving only UMNs).
Cannabis: There are no clinical trials on the use of cannabinoids for spasticity in ALS. Survey data of small number of patients with ALS report subjective reduction in spasticity symptoms.3,5
Cramping
Cramping is a major symptom in about a quarter of people with ALS and likely due to muscle denervation.
Nonprescription interventions that have anecdotally been described to alleviate ALS-related cramps include magnesium supplementation and sipping up to a quarter cup of pickle juice at cramp onset.
Internationally, quinine sulfate is used, but in the United States, cramping is not an approved indication. 2
Mexiletine is a sodium-channel blocker that reduced ALS-related cramp frequency and severity in a placebo-controlled trial. 6 Usual dose is 300 mg per day and appears to be well tolerated. 6
Pain with neuropathic features
Pain with neuropathic features such as burning, tingling, shooting, or allodynia has been reported in ALS, but it is not thought to be common.1,3 The mechanism is unclear. It is generally treated symptomatically, as most patients have already undergone electromyography as part of their ALS diagnosis. There are no studies on the efficacy of drugs for neuropathic pain management in ALS. The most used pharmacotherapies include:
gabapentin or pregabalin (side effects: drowsiness, could be helpful in those with sleep difficulties); SNRIs such as venlafaxine or duloxetine (side effects: GI symptoms, decreased libido); Tricyclic antidepressants (side effects: dry mouth, delirium, AV conduction delay, sedation).
Secondary Nociceptive Pain
Most frequently due to joint pain (especially neck and back) from reduced mobility and spinal muscle weakness. Pain from soft tissue injury from immobility is also common.
Nonpharmacological interventions
RoM exercises, warm and cold compresses, transcutaneous electrical stimulation.
Assistive devices such as pressure-relieving mattresses/pillows, custom-fit wheelchairs, or cervical collars for neck drop to minimize secondary injury. Early referrals to PT, OT, and physical medicine and rehabilitation specialists can help patients get outfitted with the appropriate devices.
Prolonged noninvasive ventilation (e.g., bilevel support) use can lead to pressure-related skin changes, especially on the bridge of the nose. Mitigation strategies include implementing rest periods off bilevel support or using a nasal mask during the day and orofacial mask at night.
Pharmacological strategies
First line agents are typically NSAIDs, acetaminophen, and topical agents such as diclofenac gel and lidocaine. 7
Opioids may be needed in advanced stages. A cohort study suggested that they can effectively relieve pain and dyspnea in advanced ALS. 8 For patients who are opioid naive, start with low oral immediate release (IR) doses (e.g., morphine IR 1–5 mg as needed) and titrate carefully based on response and side effects since many patients with ALS have a lower respiratory reserve. One study for ALS-induced pain showed efficacy with a mean morphine equivalent dose of 30 mg per day. 8
If long-acting opioids are utilized, nonoral formulations (buprenorphine patch) or formulations that can be administered through a gastrostomy tube (e.g., methadone, or specific formulations of morphine or oxycodone) are often selected since dysphagia is common in advanced ALS. Alternatively, clinicians could utilize short-acting agents in a scheduled manner in lieu of long-acting opioids. Fentanyl patches in general are used less frequently since opioid requirements are often low.
Intra-articular steroid/lidocaine injections can be considered. The duration of pain relief varies by agent used, but typically lasts for weeks.