Treatment of Chronic Pain with Acute Exacerbation
When a patient with controlled chronic pain reports new or worsening pain, immediately investigate for new pathology (infection, medication adverse effects, disease progression) rather than simply increasing existing analgesics—this new symptom requires thorough reevaluation and may necessitate added treatments or dose adjustments only after determining the underlying cause. 1
Initial Assessment of Pain Exacerbation
When chronic pain patients report acute worsening, systematically determine whether the exacerbation represents:
- New pathology requiring investigation: New opportunistic infections, adverse medication effects, or emerging comorbid conditions that demand specific treatment 1
- End-of-dose failure: The current analgesic loses effectiveness before the next scheduled dose, indicating tolerance development 1
- Treatment-resistant pain: The pain type is not responsive to the current regimen and requires a different therapeutic approach 1
- Psychosocial disruption: Life stressors interfering with the patient's usual pain self-management capacity 1
Document the new symptom comprehensively and consult with pain specialists when available 1. Use the ultra-brief PEG tool (Pain intensity, Enjoyment of life, General activity) for rapid assessment in busy clinical settings 1, 2.
Multimodal Treatment Algorithm for Exacerbations
First-Line Non-Pharmacological Interventions
Cognitive Behavioral Therapy (CBT) should be initiated or intensified for pain exacerbations, as it promotes adaptive behaviors (engaging in physical activity) while addressing maladaptive ones (avoiding activity due to fear of pain or reinjury) 1, 2. CBT also develops coping strategies specifically for anxiety related to new or worsening pain 1.
Physical and occupational therapy are strongly recommended and should be adjusted to address the specific exacerbation pattern 1, 2.
Yoga is strongly recommended specifically for chronic neck/back pain, headache, rheumatoid arthritis, and general musculoskeletal pain exacerbations 1, 2.
Hypnosis is strongly recommended when the exacerbation involves neuropathic pain components 1, 2.
Pharmacological Management Based on Pain Mechanism
For Neuropathic Pain Exacerbations
Gabapentin is the first-line oral pharmacological treatment, titrating to 2400 mg per day in divided doses 1. Gabapentin also improves sleep scores, which is particularly valuable during pain exacerbations 1.
If gabapentin provides inadequate response, consider serotonin-norepinephrine reuptake inhibitors (SNRIs like duloxetine or venlafaxine) or tricyclic antidepressants based on their effectiveness in the general population 1.
For Musculoskeletal Pain Exacerbations
Acetaminophen up to 3 grams daily is the safest first-line option, particularly in patients with liver disease, heart problems, or kidney disease 2, 3.
NSAIDs may be used cautiously but must be avoided in patients with cirrhosis (risk of GI bleeding, ascites decompensation, nephrotoxicity) and kidney stones (worsens renal function) 2, 3.
For Breakthrough Pain in Opioid-Treated Patients
Small amounts of short-acting opioid analgesics should be prescribed for acute exacerbations in patients at low risk for opioid misuse 1. Providers and patients must agree on the number of pills dispensed, frequency of use, and expected treatment duration 1.
Adjuvant therapy appropriate to the pain syndrome should be used for mild-to-moderate breakthrough pain, including non-pharmacologic treatments, steroids, non-opioid analgesics, and topical agents 1.
Special Populations
Patients on Methadone Maintenance
Split methadone into 6-8 hour doses to lengthen active analgesic effects and achieve continuous pain control during exacerbations 1, 2. Add 5-10% of the current methadone dose as afternoon and evening doses for a total 10-20% increase over the regular opioid use disorder treatment dose 1.
If additional methadone prescribing is not possible (OTP policy restrictions, high baseline dose, prolonged QTc intervals, high diversion risk), add mechanism-specific medications like gabapentin for neuropathic pain or NSAIDs for musculoskeletal pain 1.
Patients on Buprenorphine Maintenance
Increase buprenorphine dosage in divided doses (4-16 mg in 8-hour intervals) as the initial step 1, 2. If maximal buprenorphine doses are reached, add a long-acting potent opioid such as fentanyl, morphine, or hydromorphone 1.
If usual doses of additional opioids are ineffective, use closely monitored trials of higher doses, as buprenorphine's high μ-opioid receptor binding affinity may prevent lower doses of other opioids from accessing receptors 1.
For inadequate analgesia despite these strategies, transition from buprenorphine to methadone maintenance 1.
Interdisciplinary Team Activation
Develop and activate interdisciplinary teams for complex pain exacerbations, especially with co-occurring substance use or psychiatric disorders 1, 2. The team should include primary care providers, physical and occupational therapists, psychologists, case managers, and pain specialists for consultation 2.
Engage in frequent communication with the patient and their support system (family, caregivers) at a health literacy level appropriate for them 1. Schedule longer appointment times to establish and clarify goals of care 1.
Critical Pitfalls to Avoid
Do not assume existing chronic pain treatment is sufficient for new pain symptoms—this is a dangerous misconception that delays diagnosis of new pathology 1.
Do not fear adding opioids to existing regimens due to respiratory depression concerns in patients whose pain was previously controlled—this fear leads to undertreatment 1.
Do not interpret new pain reports as opioid addiction—carefully distinguish between pseudo-addiction (medication-seeking due to inadequate pain control) and true substance use disorder 1.
Avoid focusing solely on unproven interventions, as this delays implementation of evidence-based treatments 2.
Monitoring During Exacerbations
Focus assessments on achieving functional goals, decreasing pain severity, improving quality of life, and identifying treatment-related adverse events or aberrant behaviors that alter the risk-benefit ratio 1, 2.
Regular assessment of liver function, renal function, and cardiac status is essential when using pharmacological treatments 2, 3.
For patients on methadone, perform initial electrocardiogram screening to identify QTc prolongation, with interval follow-up after dose changes, especially if the patient takes other QTc-prolonging medications (certain psychotropics, fluconazole, macrolides, potassium-lowering agents) 1.