Pharmacologic management of pain in spine disorders

1

What is the definition of pain?

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.

2

What are some common criteria used to classify spinal pain?

Various criteria may be used to classify pain. For example:

• Time course: acute (<1 month), subacute (1–3 months), or chronic (>3 months)

• Intensity: mild, moderate, or severe (e.g., based on visual or numerical rating scale)

• Pathophysiology: nociceptive, neuropathic, or nociplastic

• Location: axial, radicular, or referred pain

• Presence/absence of radiation: axial non-radiating, axial radiating pain

3

Distinguish between acute and chronic pain.

Acute pain is pain of recent onset, and usually has a well-defined cause, such as peripheral nerve or tissue injury. It is expected to diminish with time or following appropriate treatment, as tissue heals and inflammation resolves. Chronic pain is pain that persists beyond its expected duration and does not respond to usual treatments. It may be the result of an initial injury or may have no clear cause. Chronic pain is often accompanied by other problems such as fatigue, sleep disturbance, changes in appetite and weight, decreased libido, and depressed mood.

4

Describe how pain is classified based on pathophysiological mechanism.

Nociceptive pain arises from actual or threatened damage to non-neural tissue due to activation of sensory neurons referred to as nociceptors by mechanical, thermal or chemical stimuli. Nociceptive pain occurs in the presence of a normally functioning somatosensory nervous system and is categorized as somatic or visceral. Somatic nociceptive pain may arise from skin, muscles, tendons, ligaments, or bone, while visceral nociceptive pain arises from thoracic, pelvic, or abdominal organs. Somatic nociceptive pain is described as localized, sharp, or dull, aching and is typically worsened by activity and decreased with rest. Examples of somatic nociceptive pain include back pain due to a lumbar strain or immediately following posterior lumbar surgery. Visceral nociceptive pain is poorly localized, described as deep, squeezing or cramping and is often associated with involvement of the autonomic nervous system leading to symptoms such as nausea, vomiting, sweating, and changes in vital signs. Examples of visceral pain include symptoms associated with myocardial infarction or appendicitis.

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Patient descriptors for neuropathic pain include burning, shooting, stabbing, electric shock-like, tingling, or numbness. Patients with neuropathic pain may exhibit pain with stimuli which are normally not painful (allodynia) or show a marked or prolonged response to painful stimuli (hyperalgesia). Neuropathic pain may be categorized by location as central (e.g., spinal cord injury related pain) or peripheral (e.g., cervical or lumbar radiculopathy).

Nociplastic pain arises from altered nociception despite lack of clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for a disease or lesion of the somatosensory nervous system. Pain is considered to arise due to persistent dysfunction of neurons throughout the central nervous system which lowers pain thresholds and amplifies sensory signaling. Examples of conditions in this category include fibromyalgia, tension headaches and cervical and lumbar pain without a structural cause.

More than one type of pain may be responsible for a patient’s pain symptoms and result in a mixed pain syndrome.

5

What pharmacologic agents are frequently used to treat spinal pain?

The most commonly prescribed medications for spinal pain include acetaminophen, nonsteroidal antiinflammatory medications (NSAIDs), antidepressants, anticonvulsants, muscle relaxants, opioids, and topical agents.

Recognition of the different types of pain is clinically important because some medications are more effective for certain types of pain. The medications of choice for nociceptive pain are analgesics. Acetaminophen and NSAIDs are recommended as first-line analgesics. While opioids are also effective, they are considered as second-line analgesics due to the risk of drug-related adverse events associated with opioid use. The medications of choice for neuropathic and nociplastic pain are anticonvulsants and antidepressants. While opioids are also effective for treatment of neuropathic pain, they are generally avoided in nociplastic pain. For treatment of patients with mixed pain syndromes, a combination of different medications may be used ( Table 15.1 ).

6

Discuss the advantages and disadvantages of the use of acetaminophen and NSAIDs.

Acetaminophen (paracetamol) and NSAIDs are first-line pharmacologic treatment options commonly prescribed for patients with spinal conditions. Acetaminophen has antipyretic and analgesic properties, but lacks antiinflammatory properties. The exact mechanism of action of acetaminophen remains incompletely understood. Although acetaminophen is less effective in providing analgesia than NSAIDs, acetaminophen has a more favorable overall safety profile. Acetaminophen has minimal effects on platelet inhibition. However, as this medication is metabolized in the liver, it is associated with the risk of hepatotoxicity and intake should not exceed the recommended maximum daily dose of 3000 mg/day.

NSAIDs provide antipyretic, antiinflammatory, and analgesic effects, mediated by inhibition of the proinflammatory enzyme cyclooxygenase (COX). NSAIDs provide more effective pain relief compared with acetaminophen, but are associated with potentially serious gastrointestinal, renal, and cardiovascular risks. As such, the lowest effective dose of NSAIDs given for the shortest duration needed for pain relief should be used. NSAIDs have variable effects depending on their chemical structure and may be classified as:

• Salicylic acids: acetylsalicylic acid (aspirin), salsalate, diflunisal

• Acetic acids: diclofenac, indomethacin, sulindac, ketorolac, etodolac, tolmetin

• Propionic acids: ibuprofen, naproxen (Naprosyn), fenoprofen, ketoprofen, oxaprozin, flurbiprofen

• Fenamic acids: sodium meclofenamate (Meclomen)

• Enolic acids (oxicams): piroxicam, meloxicam

• Nonacidic compounds: nabumetone

• COX-2 selective inhibitors: celecoxib

7

What is the difference between a selective and a nonselective NSAID?

NSAIDs may be classified as nonselective or traditional NSAIDs (e.g., aspirin, ibuprofen, naproxen) and selective NSAIDs or cyclooxygenase-2 (COX-2) inhibitors (e.g., celecoxib). Traditional NSAIDs act as nonselective inhibitors of the COX enzyme and inhibit both cyclooxygenase-1 (COX-1) and COX-2 enzymes. Selective NSAIDs were developed in an attempt to provide antiinflammatory action without the gastrointestinal adverse drug reactions attributed to inhibition of the COX-1 enzyme. Although clinical studies have shown COX-2 selective inhibitors reduce the risk of NSAID-related ulcers and complications by half when compared with traditional NSAIDs, other clinical studies have also revealed an increased incidence of adverse cardiac effects (e.g., myocardial infarction and cardiovascular death) with the use of COX-2 inhibitors when compared with non-selective NSAIDs. Given the increased incidence of adverse cardiovascular effects, and the finding that use of a proton pump inhibitor (e.g., omeprazole, 20 mg daily) with a traditional NSAID achieves a similar gastrointestinal risk profile without increasing the risk of cardiac events, the use of COX-2 inhibitors has declined.

All NSAIDs also increase the risk of hemodynamically mediated acute kidney injury. NSAIDs are not recommended for use in high-risk patients, such as those with a history of chronic kidney disease, electrolyte abnormalities (i.e., hypercalcemia), and nephrotic syndrome. Monitoring of hemoglobin, electrolytes, renal function, liver function, and blood pressure is recommended for patients maintained on NSAIDs, especially for elderly patients. Aspirin and traditional NSAIDs inhibit platelet aggregation through a COX-1-mediated effect. Concomitant use of aspirin for secondary prevention of cardiovascular disease and traditional NSAIDs is associated with increased gastrointestinal adverse events and aspirin resistance (failure to prevent thrombotic events). In patients taking aspirin for prevention of cardiovascular disease who are prescribed another NSAID, it is recommended to take aspirin at least 2 hours prior to ingestion of other NSAIDs ( Table 15.2 ).

8

When are antidepressants useful for patients with chronic spinal pain?

Antidepressant medications are commonly prescribed to treat chronic spinal pain, particularly neuropathic pain. These medications are prescribed as they have an analgesic effect, independent of their effect on depression. Options include serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g., duloxetine), tricyclic antidepressants (TCAs; e.g., amitriptyline, nortriptyline, desipramine), and selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, citalopram, fluoxetine, sertraline). Duloxetine, a prototypical SNRI, has shown effectiveness in treating pain and improving function in people with chronic axial nonradiating pain. TCAs may be considered for use in certain patients with axial nonradiating spinal pain, especially in those who have difficulty sleeping. However, duloxetine seems to be a more effective and safer alternative than TCAs if there are no contraindications to SNRI use. Although SSRIs are not as effective for pain control compared to other classes of antidepressants, they play a role in treatment due to their favorable safety profile and the overlap of symptoms due to chronic pain and depression.

9

What are some adverse effects associated with use of antidepressants for spinal pain?

SNRIs: Nausea, insomnia, dry mouth, constipation, sexual dysfunction, somnolence, and fatigue are reported adverse effects for duloxetine. Duloxetine should not be used in individuals with significant liver disease due to risk of hepatotoxicity.

TCAs: Anticholinergic adverse effects are prominent with TCA use. These effects include dry mouth, urinary retention, constipation, weight gain, blurry vision, and orthostatic hypotension. In addition, caution should be taken when prescribing TCAs to individuals with cardiac disease. TCA use in combination with other serotonergic medications increases the risk of serotonin syndrome and therefore this combination should be used with caution.

SSRIs: Adverse effects reported with SSRIs include weight gain, sexual dysfunction, sleep disturbance, headaches, dry mouth, gastrointestinal problems, and a slightly increased risk of bleeding due to platelet dysfunction ( Table 15.3 ).