Increased pain is significantly associated with lower levels of health, social function, and vitality.1 The results of studies on animal models of neuropathic pain suggest that the abnormal excitability of dorsal horn neurons in spinal muscular atrophy (SMA) may lead to neuropathic pain.2 However, other studies suggest that, unlike with other progressive neuromuscular diseases, pain in adult SMA is experienced neither more frequently nor more severely than it is in the general U.S. population. Overall, pain in this population of SMA patients appears to be comparable to that of people with osteoarthritis or chronic low back pain.1Â
Despite SMA patients being generally protected from severe pain, younger SMA patients do experience pain at heightened rates. A study on pain in adolescents with SMA or muscular dystrophy found that 69 percent of people with these muscular disorders had experienced pain in the previous three months and that 50 percent experienced chronic pain.3 The pain was most commonly felt in the neck, back, and legs, and affected both general activity and mood. Pain was exacerbated by physical exertion, sitting, and being lifted or transferred.Â
Some SMA patients experience pain as a result of orthopedic causes, from conditions such as bone deformities related to contractures, the severity of which greatly predicts the level of relevant discomfort.4 These bone deformities are often the result of genetic mutations.5 Sporadic hip pain has also been reported in some patients without positioning problems.6
Antisense oligonucleotides, which are used to treat children with SMA and are being tested in clinical trials for other neurological disorders, have been shown to ameliorate mechanical pain by suppressing RNA in nociceptive neurons. The analgesic effects have been demonstrated to last up to four weeks.7Â
Managing pain that may arise for reasons independent of SMA – like pain related to surgery – is complicated by SMA patients’ muscle weakness and hypersensitivity to certain neuromuscular blocking agents and succinylcholine-induced hyperkalemia.8 As a result of the risks of general anesthesia, spinal anesthesia and local anesthesia are the preferred methods for achieving anesthesia in this set of patients.9
To avoid muscle relaxants and tracheal intubation, surgeons have successfully employed these types of anesthesia in SMA patients to manage pain associated with a variety of procedures. For instance, epidural anesthesia has been used on SMA type 3 patients for Cesarean section deliveries,10 and local anesthesia of the temporomandibular joint has enabled dental treatment.9 Other studies have found that a combination of nondepolarizing muscle relaxants and target-controlled infusion of remifentanil and propofol can be safely used to achieve anesthesia in SMA type 4 patients.11 Finding the best way to manage pain in SMA can be an important way to mitigate the reduced quality of life observed in SMA patients and their caregivers.12
References
1. Abresch RT, Carter GT, Jensen MP, Kilmer DD. Assessment of pain and health-related quality of life in slowly progressive neuromuscular disease. Am J Hosp Palliat Care. 2002;19(1):39-48. doi:10.1177/104990910201900109
2. Lee SJ, Seo AJ, Park BS, Jo HW, Huh Y. Neuropathic pain model of peripheral neuropathies mediated by mutations of glycyl-tRNA synthetase. J Korean Med Sci. 2014;29(8):1138-1144. doi:10.3346/jkms.2014.29.8.1138
3. Lager C, Kroksmark A-K. Pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy. Eur J Paediatr Neurol. 2015;19(5):537-546. doi:10.1016/j.ejpn.2015.04.005
4. Willig TN, Bach JR, Rouffet MJ, Krivickas LS, Maquet C. Correlation of flexion contractures with upper extremity function and pain for spinal muscular atrophy and congenital myopathy patients. Am J Phys Med Rehabil. 1995;74(1):33-38.
5. Fleming J, Quan D. A case of congenital spinal muscular atrophy with pain due to a mutation in TRPV4. Neuromuscul Disord. 2016;26(12):841-843. doi:10.1016/j.nmd.2016.09.013
6. Haaker G, Fujak A. Proximal spinal muscular atrophy: current orthopedic perspective. Appl Clin Genet. 2013;6(11):113-120. doi:10.2147/TACG.S53615
7. Mohan A, Fitzsimmons B, Zhao HT, et al. Antisense oligonucleotides selectively suppress target RNA in nociceptive neurons of the pain system and can ameliorate mechanical pain. Pain. 2018;159(1):139-149. doi:10.1097/j.pain.0000000000001074
8. Kim SJ, Kim EJ, Min BW, Ban JS, Lee SG, Lee JH. Epidural anesthesia for the patient with type IV spinal muscular atrophy -A case report-. Korean J Anesthesiol. 2010;59 Suppl:S65-8. doi:10.4097/kjae.2010.59.S.S65
9. Chi SI, Kim HJ, Seo K-S, Lee JH, Chang J. Local anesthesia of the temporomandibular joint to reduce pain during mouth opening for dental treatment in a patient with spinal muscular atrophy. J Dent Anesth pain Med. 2016;16(2):137-140. doi:10.17245/jdapm.2016.16.2.137
10. Gaca M, Kokot N, Koziolek A, Kuczkowski KM. Combined spinal epidural anesthesia for cesarean section in a parturient with spinal muscle atrophy type III (Kugelberg-Walendar disease). J Matern Fetal Neonatal Med. 2011;24(1):195. doi:10.3109/14767058.2010.482617
11. Liu X-F, Wang D-X, Ma D. Using General Anesthesia plus Muscle Relaxant in a Patient with Spinal Muscular Atrophy Type IV: A Case Report. Case Rep Anesthesiol. 2011;2011:743587. doi:10.1155/2011/743587
12. Lopez-Bastida J, Pena-Longobardo LM, Aranda-Reneo I, Tizzano E, Sefton M, Oliva-Moreno J. Social/economic costs and health-related quality of life in patients with spinal muscular atrophy (SMA) in Spain. Orphanet J Rare Dis. 2017;12(1):141. doi:10.1186/s13023-017-0695-0