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Identifying and Treating Pain Caused by MS

Lance J. Wright, MD

Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee

Multiple sclerosis (MS) is a chronic disease that causes increasing disability due to inflammation and demyelination in the central nervous system. Pain is a common symptom of MS, with as many as 75% of patients reporting pain over the course of the illness and about 50% of patients reporting pain at any given time.1 More than half of MS patients with pain experience 2 or more pain syndromes, and two-thirds report that their pain symptoms are insufficiently treated by their physician.2 Pain in MS is associated with decreased functioning and an increased prevalence of depression,3 as well as a decreased quality of life.1 Although MS is incurable, pain is a treatable aspect of the illness and should, therefore, be routinely assessed and appropriately treated.

Types of MS-Related Pain

Pain syndromes in patients with MS can be divided into 2 main categories: central neuropathic pain and nociceptive pain. Clinicians need to determine the type of pain syndrome causing the symptoms in order to choose the optimal therapy (AV 1).2 Because patients with MS may have pain symptoms caused by more than one syndrome, more than one treatment may be necessary.

AV 1. Algorithm for the Diagnosis of Pain in Patients With MS (0:38)

AV 1. Algorithm for the Diagnosis of Pain in Patients With MS

Central neuropathic pain. The most common type of MS-associated pain is central neuropathic pain, or pain due to a lesion affecting the somatosensory system—ie, a lesion that causes damage in, and alterations to, the pain-sensing mechanisms in the central nervous system.4 Among the central neuropathic pain syndromes, dysesthetic extremity pain is the most common condition reported by MS patients.1,5 Usually a chronic condition, dysesthetic extremity pain is a persistent burning, stinging, or aching pain that typically affects feet and legs bilaterally (but can be unilateral), although sometimes truncal pain is present. Central dysesthesia may be worse at night and may be exacerbated by physical activity. The pain can be girdling or band-like, or can be similar to unilateral radicular pain that follows the nerve; conversely, the pain may be diffuse, widespread, multifocal, or changing. Other diagnoses, such as musculoskeletal pain and peripheral neuropathy, should be ruled out when diagnosing dysesthetic extremity pain.

Another central neuropathic pain syndrome more common in patients with MS than in the general population is trigeminal neuralgia.1 Trigeminal neuralgia is a sharp, episodic stabbing or electric shock–like pain, typically felt on one side of the lower face, which may occur spontaneously or may be triggered by external stimuli, including eating, drinking, or shaving. A neuroimaging study6 suggested that this pain condition in MS patients may be due to a lesion along the intrapontine part of the trigeminal primary afferents. The differential diagnosis for trigeminal neuralgia includes temporomandibular disorder, pulpitis, and paroxysmal hemicrania.

Lhermitte’s sign is a very brief, electric shock–like sensation, usually felt in the neck or down the spine, resulting from neck flexion- or extension-induced electrical activity in the cervical spinal cord.7 The pain immediately ceases with relaxation of the neck, and the condition usually resolves within 4 to 6 weeks (but can recur). In addition to Lhermittte’s sign, MS patients may also have other brief pains from electrical activity elsewhere in the brain or spinal cord.

Nociceptive pain. Patients with MS may experience nociceptive pain, ie, normally processed pain occurring from noxious stimuli, due to spasticity and increased muscle tone. Muscle tightness, including contracture, can cause muscle and joint pain and muscle cramping. About 11% of MS patients have painful tonic spasms, ie, intermittent muscle contractions that usually occur in the lower extremities.5 Back pain is also frequently reported by MS patients; abnormal gait or posture due to disabilities caused by MS can contribute to lower back pain, as well as knee and hip pain.

Some nociceptive pain symptoms may be directly related to MS treatments. For example, most medications for MS require frequent injections that can cause injection site pain, and some cause adverse effects, including myalgia. Headaches are more common in patients with MS than in the general public and may be worsened by interferon beta treatment.1

Treatments for MS-Related Pain Syndromes

Once the origin of the painful symptoms has been determined, appropriate treatment can begin (AV 2). Often, a multidisciplinary approach that includes patient education, physical therapy, and pharmacotherapy will be needed.

AV 2. MS-Related Pain Syndromes and Recommended Treatments (0:23)

AV 2. MS-Related Pain Syndromes and Recommended Treatments

Central neuropathic pain. Few randomized, controlled trials have examined the efficacy of medications for treating central neuropathic pain in patients with MS. However, studies8,9 of first-line treatments for neuropathic pain syndromes show similar efficacy for tricyclic antidepressants (TCAs), opioids, and the anticonvulsants gabapentin and pregabalin. Additional suggested medications for central neuropathy include other anticonvulsants, such as lamotrigine and carbamazapine,10 as well as benzodiazepines (also helpful with the emotional component of pain) and divalproex sodium. In addition to the TCAs, newer nonselective reuptake inhibitors, such as venlafaxine, desvenlafaxine, and duloxetine, may be prescribed for central pain.8

Baclofen, an antispasmodic agent, suppresses central neuropathic pain when administered intrathecally in patients with spinal lesions.11 Other drugs administered by an implanted intrathecal pump to treat central pain include opioids, ziconotide, bupivacaine, and clonidine.12,13 Dorsal column stimulation may also be considered for neuropathic pain.

For trigeminal neuralgia or persistent cases of Lhermitte’s sign, carbamazepine is the first-line treatment, but oxcarbazepine, gabapentin, pregabalin, lamotrigine, phenytoin, and divalproex sodium are also used.2,5 Oral baclofen can be effective but may not be appropriate for patients without severe spasticity, and surgery is an option for drug-resistant cases.2

Nociceptive pain. Treatment for painful symptoms due to spasticity and muscle tightness or contracture should include pharmacotherapy, patient education, preventive techniques, physical therapy, and, if necessary, surgery. Drugs that treat spasticity and, therefore, the pain associated with it include intrathecal baclofen (usually the most effective for severe cases), oral baclofen, benzodiazepines, tizanidine, and gabapentin. Focal spasticity is not generally helped with systemic drugs, but botulinum toxin type A in conjunction with antispastic drugs and physiotherapy is a useful treatment option.2 The most effective treatments for painful tonic spasms appear to be carbamazepine and gabapentin, and botulinum toxin may also help.5

For patients who experience injection site pain, optimizing injection technique and using cool packs and a topical anesthetic can help.2 Medication-related myalgia can be treated or prevented with acetaminophen, ibuprofen or other NSAIDs, or low-dose corticosteroids, and iatrogenic headaches should be closely monitored and treated appropriately. When new pain symptoms appear during an exacerbation of MS, corticosteroid pulse therapy, the standard treatment for acute relapse in MS, should be administered.

Patients should be educated about the role of abnormal gait and postures in causing pain, and trained in appropriate postures and compensation techniques. For this type of pain, physical therapy, mechanical aids, and acetaminophen and NSAIDs may be appropriate.

Summary

Patients with MS commonly suffer from painful symptoms that are not sufficiently treated. Patients may experience central neuropathic pain due to lesions in the somatosensory system and nociceptive pain due to spasticity, muscle tightness, abnormal gait or posture, and treatment-induced pain. Physicians should determine the origin of painful symptoms and then treat them appropriately using a multidisciplinary approach that includes patient education, physical therapy, and pharmacotherapy. TCAs, anticonvulsants, and opioids are first-line treatment options for central neuropathic pain. Baclofen, tizanidine, benzodiazepines, and anticonvulsants, as well as botulinum toxin, are helpful for pain due to spasticity or muscle tightness. The overall goal of pain treatment in MS is to improve patients’ functioning and quality of life, and, with patient education, physical therapy, and pharmacotherapy, this goal is achievable.

For Clinical Use
  • Routinely assess patients with MS for central neuropathic and nociceptive pain syndromes
  • Prevent or treat any medication-related or abnormal gait or posture-caused pain
  • Treat central neuropathic and nociceptive pain symptoms with appropriate interventions, including pharmacotherapy
Drug Names

baclofen (Gablofen, Lioresal, and others), botulinum toxin type A (Botox, Dysport, and others), bupivacaine (Exparel, Marcaine, and others), carbamazapine (Carbatrol, Equetro, and others), clonidine (Catapres, Duraclon, and others), desvenlafaxine (Pristiq), divalproex sodium (Depakote and others), duloxetine (Cymbalta), gabapentin (Neurontin, Gralise, and others), lamotrigine (Lamictal and others), oxcarbazepine (Trileptal and others), phenytoin (Dilantin, Phenytek, and others), pregabalin (Lyrica), tizanidine (Zanaflex and others), venlafaxine (Effexor and others), ziconotide (Prialt)

Abbreviations

MS = multiple sclerosis
NSAID = nonsteroidal anti-inflammatory drug
TCA = tricyclic antidepressant

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References
  1. O'Connor AB, Schwid SR, Herrmann DN, et al. Pain associated with multiple sclerosis: systematic review and proposed classification. Pain. 2008;137(1):96–111. PudMed
  2. Pöllmann W, Feneberg W. Current management of pain associated with multiple sclerosis. CNS Drugs. 2008;22(4):291–324. PubMed
  3. Grau-López L, Sierra S, Martínez-Cáceres E, et al. Analysis of the pain in multiple sclerosis patients [in Spanish]. Neurologia. 2011;26(4):208–213. PubMed
  4. Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70(18):1630–1635. PubMed
  5. Solaro C, Messmer Uccelli M. Pharmacological management of pain in patients with multiple sclerosis. Drugs. 2010;70(10):1245–1254. PubMed
  6. Cruccu G, Biasiotta A, Di Rezze S, et al. Trigeminal neuralgia and pain related to multiple sclerosis. Pain. 2009;143(3):186–191. PubMed
  7. Al-Araji AH, Oger J. Reappraisal of Lhermitte's sign in multiple sclerosis. Mult Scler. 2005;11(4):398–402. PubMed
  8. Attal N, Cruccu C, Haanpää M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006;13(11):1153–1169. PubMed
  9. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289–305. PubMed
  10. Finnerup NB, Gottrup H, Jensen TS. Anticonvulsants in central pain. Expert Opin Pharmacother. 2002;3(10):1411–1420. PubMed
  11. Herman RM, D'Luzansky SC, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions: a pilot study. Clin J Pain. 1992;8(4):338–345. PubMed
  12. McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3(1):69–85. PubMed
  13. Krames E. Implantable devices for pain control: spinal cord stimulation and intrathecal therapies. Best Pract Res Clin Anaesthesiol. 2002;16(4):619–649. PubMed
From the Series:
Multiple Sclerosis Syndromes and Symptoms: A Clinical Primer

Independently developed by the CME Institute of Physicians Postgraduate Press, Inc.

CME Background Information

Independently developed by the CME Institute of Physicians Postgraduate Press, Inc.

Objective

After completing this educational activity, you should be able to:

  • Recognize and appropriately manage pain in patients with MS

Financial Disclosure

The faculty for this CME activity and the CME Institute staff were asked to complete a statement regarding all relevant personal and financial relationships between themselves or their spouse/partner and any commercial interest. The CME Institute has resolved any conflicts of interest that were identified. No member of the CME Institute staff reported any relevant personal financial relationships. Faculty financial disclosure is as follows:

Dr Wright received an honorarium from Biogen for attending one advisory panel meeting.

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The American Academy of Physician Assistants (AAPA) accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 0.5 hours of Category I credit for completing this program.

To obtain credit for this activity, study the material and complete the CME Posttest and Evaluation.

Release, Review, and Expiration Dates

This Neurology Report was published in January 2012 and is eligible for AMA PRA Category 1 Credit™ through January 31, 2015. The latest review of this material was December 2011.

Statement of Need and Purpose

MS is one of the most common diseases of the central nervous system. It has an unpredictable course and the prognosis for this disorder is highly variable. Individuals with MS will typically live a normal life span, but they may experience a variety of symptoms that will reduce their quality of life, such as pain, fatigue, and spasticity. Disease-modifying drugs can help reduce the number of relapses and slow down disease progression, but they do nothing to alleviate these burdensome symptoms of the disease. Clinicians need to be aware of the importance of addressing these symptoms so that their patients with MS can experience optimal functioning and quality of life. This activity was designed to meet the needs of participants in CME activities provided by the CME Institute of Physicians Postgraduate Press, Inc., who have requested information on multiple sclerosis.

Disclosure of Off-Label Usage

Dr Wright has determined that carbamazapine, desvenlafaxine, divalproex sodium, duloxetine, gabapentin, lamotrigine, pregabalin, and venlafaxine are not approved for central neuropathic pain; baclofen, divalproex sodium, gabapentin, lamotrigine, oxcarbazepine, phenytoin, and pregabalin are not approved for trigeminal neuralgia or Lhermitte’s sign; botulinum toxin type A is not approved for focal spasticity; and botulinum toxin type A, carbamazepine, and gabapentin are not approved for tonic spasms.

Review Process

The entire faculty of the series discussed the content at a peer-reviewed planning session, the Chair reviewed the activity for accuracy and fair balance, and a member of the External Advisory CME Board who is without conflict of interest reviewed the activity to determine whether the material is evidence-based and objective.

Acknowledgment

This Neurology Report was derived from an interview with Lance J. Wright, MD, on July 8, 2011. This activity is one in a series of independent projects undertaken by the CME Institute of Physicians Postgraduate Press, Inc., as a service to its members and the broader academic and clinical community. The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher.