What are the treatment options for pain management in multiple sclerosis (MS)?

Pain Management for Multiple Sclerosis

First-line treatment for neuropathic pain in multiple sclerosis should include tricyclic antidepressants (TCAs) such as nortriptyline or desipramine, or selective serotonin norepinephrine reuptake inhibitors (SSNRIs) such as duloxetine or venlafaxine, or calcium channel α2-δ ligands such as gabapentin or pregabalin. 1

Types of Pain in Multiple Sclerosis

MS patients commonly experience multiple pain syndromes that require different treatment approaches:

• Neuropathic pain (directly related to MS) - includes ongoing extremity pain, trigeminal neuralgia, Lhermitte's phenomenon, and painful tonic spasms 2, 3
• Pain indirectly related to MS - such as spasticity-related pain and musculoskeletal pain 2
• MS treatment-related pain - including injection site pain and systemic side effects 2
• Pain unrelated to MS - such as headaches and back pain that may worsen with MS 2

Stepwise Management of Neuropathic Pain

Step 1: Assessment and Diagnosis

• Establish the diagnosis of neuropathic pain and identify the specific type of pain syndrome 1
• Identify relevant comorbidities that might affect treatment choices (cardiac, renal, hepatic disease, depression) 1
• Explain diagnosis and treatment plan to establish realistic expectations 1

Step 2: First-line Medications

• Antidepressants:

  • Secondary-amine TCAs (nortriptyline, desipramine) - start with low dosages at bedtime with slow titration 1
  • SSNRIs (duloxetine, venlafaxine) - particularly effective for peripheral neuropathic pain 1

• Anticonvulsants:

  • Calcium channel α2-δ ligands (gabapentin or pregabalin) - shown to be effective in MS-related pain 1, 4
  • For trigeminal neuralgia: carbamazepine, oxcarbazepine, or lamotrigine 2, 3

• Topical treatments:

  • Lidocaine patches (4-5%) for localized peripheral neuropathic pain 1
  • Compounded topical amitriptyline-ketamine mixture for localized pain 1

• For acute pain exacerbations:

  • Short-term opioid analgesics or tramadol may be used alone or in combination with first-line therapies 1

Step 3: Monitoring and Adjustments

• Reassess pain and quality of life frequently 1
• If substantial pain relief (pain reduced to ≤3/10) with tolerable side effects, continue treatment 1
• If partial relief (pain remains ≥4/10), add one of the other first-line medications 1
• If inadequate relief (<30% reduction), switch to an alternative first-line medication 1

Step 4: Second and Third-line Options

• For painful paroxysmal symptoms and tonic spasms:

  • Muscle relaxants (baclofen, tizanidine) 3, 5
  • Botulinum toxin injections for severe spasticity 2, 3

• For refractory pain:

  • Cannabinoids - emerging evidence for MS-related pain 2, 3, 6
  • Opioids (including low-dose naltrexone) - reserved for cases unresponsive to other treatments 3, 5
  • Referral to pain specialist or multidisciplinary pain center 1

Special Considerations

Trigeminal Neuralgia in MS

• First-line: Anticonvulsants (carbamazepine, oxcarbazepine) 1, 2
• Second-line: Lamotrigine, gabapentin, or pregabalin 1, 3
• For refractory cases: Consider neurosurgical approaches 3

Spasticity-Related Pain

• Physical therapy is foundational 2
• Antispastic agents: baclofen or tizanidine 2
• For phasic spasticity: gabapentin or levetiracetam 2
• Severe cases: botulinum toxin injections or intrathecal baclofen 2

Musculoskeletal Pain

• Optimize physical therapy and properly adjusted aids 2
• Acetaminophen or NSAIDs may provide relief 2
• Ensure proper positioning to avoid pressure lesions 2

Non-Pharmacological Approaches

• Physical therapy and exercise programs 5, 6
• Neuromodulation techniques:
  • Transcutaneous electrical nerve stimulation (TENS) 6
  • Transcranial direct current stimulation (tDCS) 6
• Psychological approaches:
  • Cognitive behavioral therapy 1, 5
  • Mindfulness-based stress reduction 3, 5

Cautions and Pitfalls

• TCAs should be used with caution in patients with cardiac disease or ventricular conduction abnormalities 1
• For patients >40 years, obtain a screening electrocardiogram before starting TCAs 1
• Limit TCA dosages to less than 100 mg/day when possible 1
• Allow adequate trial periods (6-8 weeks for TCAs, including 2 weeks at highest tolerated dose) 1
• MS patients may be more sensitive to medication side effects; cautious dose escalation is advisable, particularly with gabapentin 4
• Multiple pain syndromes often coexist in MS patients, requiring combination approaches 2