Preclinical Pain in Amyotrophic Lateral Sclerosis May Be a Marker for Diagnosis, Treatment

man holding his back in pain
man holding his back in pain
Reports of pain may indicate a preclinical course of amyotrophic lateral sclerosis.

Pain is far more common and widespread in amyotrophic lateral sclerosis (ALS) than previously suspected, and initial pain symptoms may predate the clinical onset of the disease’s hallmark motor dysfunction by as much as 2 years, reported Adriano Chiò, MD, from the University of Turin in Italy, and colleagues in a review article published recently in the Lancet.1

The investigators found pain to present in many forms throughout the course of ALS, a rare motor neuron disease characterized by severe progressive loss of upper and lower limb strength, dysarthria, dysphagia, and respiratory failure leading to death within 2 to 4 years of onset.2

Dr Chiò and colleagues performed a search of studies conducted from 1966 through 2016 and found tremendous variation in the reports of pain in ALS, ranging from less than 15% to 85%, including 2 large observational studies that failed to mention pain at all.1

When pain in ALS was assessed, it was most frequently reported as “mild,” although pain intensity as high as “unbearable” was also recorded. Pain complaints were treated pharmacologically in 50% of patients with ALS, who were found to have higher use of pain medications than reported in the general population. The types of drugs used ranged from simple analgesics and nonsteroidal anti-inflammatory drugs to cannabinoids and opioid sedatives.

One of the most interesting features was a trend toward prediagnostic pain that suggested a possible preclinical course pointing to ALS. Although direct correlations could not be traced and the investigators found no systematic studies of preclinical ALS pain, 1 study showed patients with ALS using gabapentin for neuropathic pain in the 2 years before ALS onset at rates significantly higher than the general population. In a large study of 424 patients, 318 (75%) reported pain of various types, including low back pain, arthritis, headache, surgical pain, pain from injury, or cancer pain, that started before their diagnosis of ALS. The majority of these complaints (82%) were attributed directly to ALS, and in 34% of cases, it was the triggering factor leading to diagnosis.

Pain was also present throughout the course of ALS, with some studies indicating higher frequency and severity in later stages of the disease that corresponded directly to levels of functional impairment. A large-scale population-based study reported moderate to severe pain in 52% of patients during the month before death, whereas a 2016 retrospective review of 52 hospice patients indicated uncontrolled pain on admission in at least 75% of the cohort.

This review pointed to clinical features of pain in ALS that are significantly underevaluated in clinical practice. Further clinical research should be conducted to develop targeted therapies that address pain in ALS.

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  1. Chiò A, Moro G, Lauria G. Pain in amyotrophic lateral sclerosis. Lancet Neurol. 2017;16:144-157. doi: 10.1016/S1474-4422(16)30358-1
  2. Chiò A, Brunetti M, Barberis M, et al. The role of APOE in the occurrence of frontotemporal dementia in amyotrophic lateral sclerosis. JAMA Neurol. 2016;73:425-430. doi: 10.1001/jamaneurol.2015.4773