Multiple sclerosis and pain

The literature suggests that many of the subjects with MS are suffering pain over the progression of the disease (Seixas et al. 2011). The overall prevalence of pain in subjects with MS is between 40%-65% (Ghajarzadeh and Jalilian 2018). Foley et al., in a systematic review, indicated that the prevalence of MS-related pain ranges from 40 to 86%. Neuropathic pain, nociceptive pain and headache are the pain conditions frequently observed in this population (Solaro et al. 2018, Osterberg et al. 2014).

Central neuropathic pain (CNP) is a pain condition diagnosed in a significant percentage of MS (Ferraro et al. 2018). According to O´Connor et al. (2008), the most common central neuropathic pain conditions in subjects with MS are central neuropathic extremity pain, trigeminal neuralgia, and Lhermitte’s sign.

The central neuropathic (‘‘dysesthetic’’) extremity pain is a very common chronic pain described as a continuous burning, aching and pricking pain; normally bilateral that affected legs and feet. It is often worse at night and can be increased by physical activity. It is associated with other symptoms such as sensory abnormalities (abnormal sensibility to painful stimulus and temperature) (O´Connor et al. 2008, Ferraro et al. 2018).

Trigeminal neuralgia is relatively frequent in subjects with MS. It presents specific characteristics in this population: 11–31% of cases are bilateral, a much higher rate than in non-MS patients; patients tend to be younger than non-MS patients with trigeminal neuralgia (O´Connor et al. 2008, Ferraro et al. 2018).

Lhermitte’s sign has been defined as ‘‘a transient short-lasting sensation related to neck movement […] felt in the back of the neck, lower back or in other parts of the body’’ (Al-Araji and Oger 2005). It has been associated with MRI lesions in the posterior columns of the cervical spinal cord and is thought to be caused by hypersensitivity of demyelinated cervical sensory axons to stretching (O´Connor et al. 2008, Ferraro et al. 2018).

Although the mechanisms underlying pain in MS have not yet been clarified, it has been linked to changes of the central pathways. Some theories explaining pain in MS suggest that injury of spinothalamic pathway results in a disinhibition of descending pain pathways or an imbalance between different inputs, and that structural lesions in the central nervous system cause a state of hyperexcitability (central sensitization) by increasing neuronal activity at the site of injury and at remote sites (Fernández de las Peñas et al. 2015).

Pain and depression has a complex relationship of situational and physiological connections in subjects with MS (Ferraro et al. 2018). Pain and depression are intensely linked with MS patients. It has been emphasized that the presence or severity of one condition cross-amplifies the other (Ferraro et al. 2018, Alschuler et al. 2013).


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Alschuler KN, Ehde DM, Jensen MP. Co-occurring depression and pain in multiple sclerosis. Phys Med Rehabil Clin N Am. 2013; 24(4):703–715

Fernández-de-Las-Peñas C, Ortega-Santiago R, Ortíz-Gutiérrez R, Caminero AB, Salom-Moreno J, Arendt-Nielsen L. Widespread pressure pain hypersensitivity in patients with multiple sclerosis with and without pain as sign of central sensitization. Clin J Pain. 2015;31(1):66-72.

Folye PL, Vesterinen HM, Laird BJ, Sena ES, Colvin LA, Chandran S, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain 2013; 154(5): 535-44.

Ghajarzadeh M, Jalilian R, Sahraian MA, Moghadasi AN, Azimi A, Mohammadifar M, Azizi S. Pain in Patients with Multiple Sclerosis. Maedica (Buchar). 2018 Jun;13(2):125-130.

Grau-Lopez L, Sierra S, Martinez-Caceres E, Ramo-Tello C. Analysis of the pain in multiple sclerosis patients. Neurología. 2011;4:208-213.

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Solaro C, Cella M, Signori A, Martinelli V, Radaelli M, Centonze D, et al. Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria. J Neurol. 2018. J Neurol. 2018; 265:828–835


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