Pain Management and Opioids
TOPIC 2 SUMMARY
Common
Non-Musculoskeletal
Pain
INTRODUCTION AND GENERAL PRINCIPLES
Although musculoskeletal conditions are the most prevalent cause of chronic pain, a
range of other common conditions may also cause such pain, including neuropathic
pain syndromes, fibromyalgia, and headache.
In each of these conditions, establishing the underlying diagnosis is important and may
allow treatment of causative or exacerbating factors. For example, achieving restorative
sleep is paramount in both fibromyalgia and migraine. Similarly, although diagnosis
and adequate treatment of diabetes mellitus is necessary for controlling small-fiber
neuropathy, screening for common comorbid causes of peripheral neuropathy, such as
vitamin B12 deficiency and thyroid disease, is also important.
Once the diagnosis is made, additional nonpharmacologic therapies and pharmacologic
treatments can be initiated.
DIABETIC NEUROPATHY
Diabetic neuropathy can manifest in a variety of ways, such as:
• Painful, small-fiber neuropathy
• Entrapment neuropathy
• Diabetic amyotrophy
• Length-dependent, large-fiber sensorimotor neuropathy
Initial treatment consists of improved glycemic control, physical exercise, and gait train-
ing; pharmacologic options can be added if needed.
Topic 2: Common Non-Musculoskeletal Pain knowledgeplus.nejm.org 1
First-line medications for pain from diabetic neuropathy include:
• T
he tricyclic antidepressant (TCA) amitriptyline
• The serotonin–norepinephrine reuptake inhibitors (SNRIs) duloxetine and
venlafaxine
• The anticonvulsants pregabalin and gabapentin
When deciding among these agents, clinicians should consider each medication’s
adverse-effect profile and the individual patient’s comorbidities.
Although there are some moderate-quality data supporting the use of opioids (e.g.,
oxycodone, tramadol) for alleviating neuropathic pain, these medications are not con-
sidered first-line agents because of concerns about their overall risk–benefit ratio.
POSTHERPETIC NEURALGIA
Postherpetic neuralgia is characterized by severe neuropathic pain in a dermatomal
distribution that persists for more than 90 days after herpes zoster reactivation. The
risk of developing this condition increases with advancing age. Treatment is symp-
tomatic and can consist of topical agents, oral neuropathic pain medications, and
interventional pain techniques.
If the pain is in an accessible area (excluding the face, V1 distribution), topical therapies
can be used, such as lidocaine patches (once daily) and capsaicin cream (up to four
times daily). Typically, these agents are reasonably well tolerated except for occasional
local adverse effects such as rashes and stinging. They have limited absorption, and
systemic adverse reactions are rare.
First-line oral agents for postherpetic neuralgia include gabapentin, pregabalin, and
TCAs such as amitriptyline. A specific concern with gabapentin and pregabalin is the
risk of misuse, which is increasingly being recognized. In addition, there are consid-
erations with the use of any of these agents in older patients because of the expected
age-related decrease in therapeutic index. Specifically, all of these medications are asso-
ciated with sedation and should therefore be started at low doses, with careful monitor-
ing for adverse effects while the dose is titrated upward.
Opioids should not be used as first-line therapy in postherpetic neuralgia. Although
studies have shown mixed evidence of a benefit from opioid therapy in this clinical set-
ting, the risks of these medications — in terms of their potentially addictive properties
and adverse effects — outweigh any potential benefit, especially in older adults who are
at higher risk of adverse effects from opioids.
FIBROMYALGIA
Fibromyalgia is characterized primarily by widespread myofascial pain and often involves
chronic fatigue and sleep disturbances. Other common symptoms include cognitive dif-
ficulties, depressed mood, anxiety, headaches, and digestive problems such as irritable
bowel syndrome.
Topic 2: Common Non-Musculoskeletal Pain knowledgeplus.nejm.org 2
Guidelines from the European Alliance of Associations for Rheumatology (EULAR) offer
the most comprehensive evidence-based review of management principles for patients with
fibromyalgia. Data are mixed across large meta-analyses but generally favor the follow-
ing nonpharmacologic interventions:
• hysical exercise (recommended as first-line therapy)
P
• Acupuncture
• Cognitive behavioral therapy
• Mindfulness practice
• Meditative movement (yoga, tai chi)
Certain pharmacologic treatments have also been found to be effective, including
duloxetine and pregabalin (which are preferred if pain is the main symptom), the
SNRI milnacipran, and low-dose amitriptyline (which is preferred if insomnia is the
main symptom or if there is concurrent depression). Nonsteroidal antiinflammatory
drugs (NSAIDS), glucocorticoids, and opioids do not have a role in the management of
fibromyalgia.
MIGRAINE
Migraine headache afflicts more than 10% of the population and is a global burden
on quality of life. Therapy involves avoidance of triggers, management of risk factors,
pharmacotherapy, and other treatment modalities. Treatment options depend on the
episodic versus chronic nature of the headaches, comorbid associated features, and the
patient’s medical profile.
For an acute migraine attack, treatments include:
• N
onpharmacologic interventions, such as moving into a darkened room,
reducing light stimulation and noise levels, and engaging in osteopathic
manipulative treatment
• Acetaminophen
• Triptans, such as sumatriptan
• NSAIDs, such as ibuprofen or ketorolac
• Butalbital–acetaminophen–caffeine
• Metoclopramide (if nausea and vomiting are prominent, other antiemetics can
also be used, such as diphenhydramine, prochlorperazine, or chlorpromazine)
Opioids are almost never indicated for treatment of migraine; they are typically only
used as a last resort and then only briefly.
LEARNING RESOURCES
• Diagnosis & Treatment of Fibromyalgia: An algorithm from NEJM Knowledge+
detailing the diagnosis, evaluation, and treatment of fibromyalgia
Topic 2: Common Non-Musculoskeletal Pain knowledgeplus.nejm.org 3
• Diagnosis & Treatment of Neuropathic Pain: An algorithm from NEJM
Knowledge+ that describes how to diagnose and treat neuropathic pain,
including painful peripheral neuropathy and postherpetic neuralgia.
• Common Interventional Pain Procedures: An illustrated guide from NEJM
Knowledge+ detailing 18 of the most common interventional pain procedures
(typically considered if adequate pain relief is not achieved after an appropriate
trial of medication, at least 6 weeks of physical therapy, or both). This PDF
includes illustrations, lists of indications, clinical pearls, potential complications,
and brief instructions on how to perform the procedures.
Last reviewed Oct 2023. Last modified Oct 2023. The information included here is provided
for educational purposes only. It is not intended as a sole source on the subject matter or as
a substitute for the professional judgment of qualified health care professionals. Users are
advised, whenever possible, to confirm the information through additional sources.
© 2023 Massachusetts Medical Society. All rights reserved.
Topic 2: Common Non-Musculoskeletal Pain knowledgeplus.nejm.org 4
