What are the treatment options for chronic systemic pain?

Treatment of Chronic Systemic Pain

For chronic systemic pain, begin with non-pharmacological interventions (cognitive behavioral therapy, physical therapy, and exercise) combined with first-line pharmacological agents: gabapentin (titrated to 2400 mg/day in divided doses) for neuropathic components, or acetaminophen/NSAIDs for musculoskeletal components, avoiding opioids as first-line therapy. 1, 2

Initial Assessment and Pain Classification

Determine the predominant pain mechanism before initiating treatment, as this guides therapeutic selection 3:

• Neuropathic pain: Burning, shooting, or electric-shock sensations with sensory abnormalities 1, 4
• Nociceptive/inflammatory pain: Aching, throbbing pain related to tissue damage 3
• Central sensitization: Widespread pain with hyperalgesia and allodynia 3

Assess for comorbid mood disorders, sleep disturbances, and functional impairment, as these significantly influence treatment outcomes 3

Non-Pharmacological Interventions (First-Line for All Pain Types)

Cognitive Behavioral Therapy (CBT) is strongly recommended as it promotes adaptive behaviors and addresses maladaptive pain-related fears 1, 2. CBT should be initiated early, not reserved for treatment failures 1.

Physical activity and aerobic exercise reduce pain severity and improve physical function with minimal adverse effects 1. Exercise therapy provides sustained improvements for at least 2-6 months 1.

Additional modalities with evidence of benefit 1, 2:

• Yoga for chronic neck/back pain, headache, and musculoskeletal pain 1, 2
• Physical and occupational therapy 1, 2
• Hypnosis specifically for neuropathic pain 1, 2
• Acupuncture may be considered as a trial, though evidence is more limited 1, 2

Pharmacological Management Algorithm

Step 1: First-Line Agents

For neuropathic or mixed pain:

• Gabapentin starting at 300 mg at bedtime, titrated to 2400 mg daily in three divided doses 1, 2
• Gabapentin improves both pain and sleep scores; somnolence occurs in 80% of patients 1

For musculoskeletal/nociceptive pain:

• Acetaminophen or NSAIDs as initial therapy 1, 2, 5
• Use lower acetaminophen doses in liver disease 2
• Consider cardiovascular risk with COX-2 selective NSAIDs 2, 6
• NSAIDs carry risks of gastrointestinal bleeding, which increases with corticosteroid/anticoagulant use, prolonged duration, smoking, alcohol, and advanced age 6

Topical agents for localized pain:

• Capsaicin 8% patch: Single 30-minute application provides relief for up to 12 weeks 1, 2, 5
• Lidocaine 5% patches for localized neuropathic pain 1

Step 2: Second-Line Agents (If Inadequate Response to First-Line)

For neuropathic pain:

• Pregabalin 75-300 mg every 12 hours 1, 2, 7
• Duloxetine or other serotonin-norepinephrine reuptake inhibitors (SNRIs) 1, 2, 4
• Duloxetine shows small improvements in pain intensity and function 1

For mixed or musculoskeletal pain:

• Tricyclic antidepressants (amitriptyline preferred) 1, 2, 4
• TCAs have more side effects than SNRIs but may be effective for chronic pain with sleep disturbance 4, 5

Alternative considerations:

• Venlafaxine up to 75 mg daily 1
• Tramadol for moderate pain, though it provides only moderate short-term relief 1, 5

Step 3: Third-Line Options (For Refractory Cases)

Sodium channel blockers (trial for 3-4 months each) 1:

• Mexiletine
• Carbamazepine

Selective serotonin reuptake inhibitors (SSRIs) 1:

• Sertraline preferred over fluoxetine 1
• Note: Moderate-quality evidence shows no difference in pain between SSRIs and placebo for chronic low back pain 1

Step 4: Specialized Pain Management

If pain remains refractory to the above treatments or is associated with chronic pain syndrome, referral to a pain rehabilitation center should be considered 1

Palliative care consultation is recommended for advanced illness with uncontrolled pain to assist with symptom management and goals of care 1

Medications to Avoid or Use with Extreme Caution

Opioids should NOT be first-line agents for chronic systemic pain due to risks of pronociception, cognitive impairment, respiratory depression, endocrine/immunological changes, and addiction 1, 2. If opioids are considered after failure of all other options, they must be combined with non-pharmacological therapy, used at the lowest effective dose for the shortest duration, with opioid treatment agreements and urine drug testing 1, 2.

Avoid repeated use of NSAIDs or corticosteroids for chronic daily non-inflammatory pain 1

Benzodiazepines have limited evidence for chronic pain efficacy and carry risks of dependence 1

Lamotrigine is not recommended for neuropathic pain due to rash risk and limited efficacy 2

Critical Monitoring and Safety Considerations

Regular reassessment of pain intensity, functional improvement, and medication side effects is essential 2. Longer appointment times may be necessary to establish and clarify goals of care 1.

Common pitfalls to avoid:

• Prescribing medications without concurrent non-pharmacological interventions 1
• Using opioids as first-line therapy 1, 2
• Failing to address comorbid mood and sleep disorders 3
• Not titrating gabapentin to adequate doses (many patients require 2400 mg/day) 1
• Discontinuing effective treatments prematurely (trials should last 3-4 months) 1

Multidisciplinary communication between medical providers, the patient, and the patient's support system is critical to maintaining pain control 1