# Chronic Pain Management: A Multimodal Approach

## Introduction

Chronic pain, defined as pain persisting beyond 3 months, affects over 50 million US adults and is the leading cause of disability worldwide. The failed paradigm of opioid-centric pain management contributed to an ongoing addiction and overdose crisis. Modern pain management emphasizes a **biopsychosocial model** with multimodal therapies targeting the physical, psychological, and social dimensions of pain. Internal medicine residents must be comfortable initiating evidence-based non-opioid therapies and managing opioids safely when indicated.

## Pain Neuroscience

- **Nociceptive pain**: caused by tissue damage activating peripheral nociceptors (somatic or visceral)
- **Neuropathic pain**: caused by lesion or disease of the somatosensory nervous system (burning, shooting, tingling)
- **Nociplastic pain** (central sensitization): amplified central nervous system processing without clear nociceptive input (fibromyalgia, chronic widespread pain, irritable bowel syndrome)
- **Peripheral and central sensitization**: repeated nociceptive input leads to reduced pain thresholds, expanded receptive fields, and pain from normally non-painful stimuli (allodynia)
- Identifying the pain mechanism guides pharmacotherapy selection

## Assessment

- **Pain history**: location, quality, intensity (0-10 NRS), temporal pattern, aggravating/alleviating factors, prior treatments
- **Functional impact**: PEG scale (Pain, Enjoyment of life, General activity); functional goals are more meaningful than pain scores
- **Psychosocial assessment**: depression, anxiety, catastrophizing, social isolation, adverse childhood experiences
- **Screen for substance use disorder**: Opioid Risk Tool (ORT), SOAPP-R; urine drug testing
- **Red flags**: unexplained weight loss, fever, neurologic deficits, progressive weakness (evaluate for malignancy, infection, cauda equina)

![Biopsychosocial model of chronic pain assessment](images/chronic-pain-biopsychosocial.png)

## Non-Pharmacologic Therapies

### Physical and Rehabilitative

- **Exercise therapy**: strongest evidence base; aerobic exercise, resistance training, yoga, tai chi all reduce pain and improve function in chronic low back pain, osteoarthritis, and fibromyalgia
- **Physical therapy**: graded exercise programs, manual therapy, activity modification
- **Cognitive behavioral therapy (CBT)**: restructures maladaptive pain beliefs and catastrophizing; NNT of 2-4 for clinically meaningful improvement
- **Acceptance and commitment therapy (ACT)**: emphasizes psychological flexibility and value-based living despite pain
- **Mindfulness-based stress reduction (MBSR)**: demonstrated benefit in chronic low back pain (JAMA 2016)

### Interventional Procedures

- **Epidural steroid injections**: short-term relief for lumbar radiculopathy; limited evidence for long-term benefit
- **Facet joint interventions**: medial branch blocks followed by radiofrequency ablation for facet-mediated pain
- **Spinal cord stimulation**: for failed back surgery syndrome and complex regional pain syndrome
- **Trigger point injections**: for myofascial pain syndrome
- **Nerve blocks**: peripheral nerve blocks for localized neuropathic pain

## Non-Opioid Pharmacotherapy

### First-Line Agents by Pain Type

| Pain Type | First-Line Agents | Dose Range | NNT |
|-----------|------------------|------------|-----|
| Neuropathic | Gabapentin | 300-3600 mg/day | 6-7 |
| | Pregabalin | 150-600 mg/day | 6-7 |
| | Duloxetine (SNRI) | 60-120 mg/day | 6-7 |
| | TCAs (amitriptyline, nortriptyline) | 25-150 mg QHS | 3-4 |
| Musculoskeletal | Acetaminophen | Up to 2 g/day (chronic) | Variable |
| | Topical NSAIDs (diclofenac gel) | Per joint | ~6 |
| | Duloxetine | 60-120 mg/day | 5-7 |
| Nociplastic (fibromyalgia) | Duloxetine | 60-120 mg/day | 8 |
| | Pregabalin | 300-450 mg/day | 9 |
| | Milnacipran | 100-200 mg/day | 10 |

#### Neuropathic Pain

- **Gabapentinoids**: gabapentin (300-3600 mg/day), pregabalin (150-600 mg/day); NNT 6-7 for 50% pain relief
- **SNRIs**: duloxetine (60-120 mg/day), venlafaxine (150-225 mg/day); also effective for comorbid depression
- **Tricyclic antidepressants**: amitriptyline, nortriptyline (25-150 mg at bedtime); NNT 3-4; anticholinergic side effects limit use in elderly
- **Topical lidocaine** (5% patch): for localized neuropathic pain, minimal systemic absorption
- **Topical capsaicin** (8% patch): for postherpetic neuralgia, HIV-associated neuropathy

#### Musculoskeletal Pain

- **Acetaminophen**: up to 2 g/day in chronic use (reduced ceiling to protect against hepatotoxicity)
- **NSAIDs**: use lowest effective dose for shortest duration; topical NSAIDs (diclofenac gel) preferred for localized osteoarthritis (comparable efficacy, fewer systemic effects)
- **Duloxetine**: FDA-approved for chronic musculoskeletal pain and osteoarthritis
- **Cyclobenzaprine**: short-term use for acute muscle spasm; avoid chronic use

#### Nociplastic Pain (Fibromyalgia)

- **Duloxetine** (60-120 mg/day): FDA-approved for fibromyalgia
- **Pregabalin** (300-450 mg/day): FDA-approved for fibromyalgia
- **Milnacipran** (100-200 mg/day): FDA-approved for fibromyalgia
- **Low-dose naltrexone** (1.5-4.5 mg/day): emerging evidence for fibromyalgia and central sensitization

![Non-opioid pharmacotherapy selection by pain mechanism](images/pain-pharmacotherapy-algorithm.png)

## Opioid Therapy: When and How

### Indications

- Moderate-to-severe pain significantly impairing function despite optimized non-opioid multimodal therapy
- Cancer pain, palliative care, and end-of-life care
- Chronic non-cancer pain: opioids should be a last resort, not a first-line therapy

### Safe Prescribing Practices (CDC 2022 Guideline)

- Start with **immediate-release opioids** at lowest effective dose
- Avoid exceeding **50 morphine milligram equivalents (MME)/day** without careful reassessment; use extreme caution above 90 MME/day
- **Co-prescribe naloxone** for all patients receiving >= 50 MME/day, history of overdose, concurrent benzodiazepine use, or substance use disorder history
- **Prescription drug monitoring program (PDMP)**: check before every new opioid prescription and periodically thereafter
- **Urine drug testing**: baseline and at least annually; confirm expected drug presence and absence of undisclosed substances
- Reassess opioid benefit every **1-3 months**; taper if risks outweigh benefits

### Opioid Tapering

- Gradual taper: reduce by 10% of total daily dose per month
- Avoid abrupt discontinuation (risk of withdrawal, destabilization, illicit opioid use)
- Optimize non-opioid pain management before and during taper
- Collaborate with addiction medicine if opioid use disorder is identified

### Opioid Use Disorder

- Screen for **OUD** using DSM-5 criteria
- **Medication-assisted treatment (MAT)**: buprenorphine/naloxone or methadone; reduces mortality by 50%
- Internal medicine residents should obtain X-waiver training (now eliminated; all DEA-registered providers can prescribe buprenorphine)

![Opioid risk mitigation and monitoring framework](images/opioid-safety-framework.png)

## Key Clinical Pearls

- Identify the pain mechanism (nociceptive, neuropathic, or nociplastic) to guide pharmacotherapy selection
- Exercise and CBT have the strongest evidence for chronic pain and should be prescribed alongside pharmacotherapy
- Duloxetine is the most versatile non-opioid analgesic, with FDA approval for neuropathic pain, fibromyalgia, chronic musculoskeletal pain, and osteoarthritis
- All providers with a DEA license can now prescribe buprenorphine for opioid use disorder; there is no longer a separate waiver requirement

## References

1. Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain -- United States, 2022. *MMWR Recomm Rep*. 2022;71(3):1-95.
2. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for Neuropathic Pain in Adults: A Systematic Review and Meta-Analysis. *Lancet Neurol*. 2015;14(2):162-173.
3. Cherkin DC, Sherman KJ, Balderson BH, et al. Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy on Back Pain and Functional Limitations. *JAMA*. 2016;315(12):1240-1249.
4. Volkow ND, Blanco C. The Changing Opioid Crisis: Development, Challenges, and Opportunities. *Mol Psychiatry*. 2021;26(1):218-233.