Applying the principles

The proper use of available medications can benefit patients with a number of difficult-to-treat pain syndomes.

Low back pain This is one of the most common pain complaints primary-care practitioners confront. A recent study found that two thirds of adults will suffer from low back pain at some time.6 An estimated 95% of Americans will have degenerative disk disease by age 50.7


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LBP can be divided into two categories; acute (resolves within 6-12 weeks no matter what therapies are used) and chronic (pain does not improve within 12 weeks).

The American College of Physicians (ACP) in conjunction with the American Pain Society (APS) have developed a joint guideline that outlines the best evidence-based recommendations for treating patients with LBP.8 The first recommendation is that clinicians perform a focused history and physical to place the patient into one of three categories: (1) nonspecific LBP (e.g., musculoskeletal strain); (2) back pain potentially associated with radiculopathy or spinal stenosis; or (3) back pain potentially associated with another spinal cause (e.g., compression fracture, tumors). The guideline also recommends assessing psychosocial factors and emotional distress, which can be strong indicators of treatment outcome.

With regard to imaging, the ACP/APS panel advises against routine use. Instead, imaging for patients with nonspecific LBP can be deferred. Prompt MRI (preferred) or CT is recommended for patients who have severe or progressive neurologic deficits or when serious underlying conditions are suspected and delay in treatment would be detrimental. In cases of persistent LBP with or without radiculopathy or suspected spinal stenosis, MRI (again preferred) or CT should be done only if the patient is a candidate for surgery or epidural steroid injection. Imaging preferences are based on a desire to reduce patient exposure to radiation, control treatment costs, and avoid less optimal outcomes with other choices.8

Once the patient is diagnosed, a treatment option must be chosen. As previously discussed, fear of addiction affects the treatment decisions of many clinicians, but most LBP patients expect to leave their clinician’s office with a prescription. In one study, 80% of primary-care patients who saw their provider for LBP were prescribed at least one medication at their initial office visit, and more than one third were prescribed two or more drugs.9

The ACP/APS guideline recommends acetaminophen and NSAIDs as first-line medication, with opioids and tramadol reserved for patients who have severe and disabling pain.8 While the risk and long-term effects associated with short-term opioid use are fairly well recognized, the effects of long-term use are less clear.10 Recently, long-term use of opioids for chronic pain has been linked to opioid hyperalgesia, an atypical increase in pain severity unrelated to the original pain stimulus.11  

Other medications to consider for LBP include muscle relaxants, tricyclic antidepressants, antiseizure medications (especially gabapentin [Neurontin]), and benzodiazepines. Of course, these medications are not benign and have side effects that some patients will find intolerable. Benzodiazepines have the potential for abuse. Systemic steroids are not indicated. Some herbal remedies (e.g., devil’s claw, capsaicin) have been found to have limited benefits.9

Nonpharmacologic recommendations for acute LBP include spinal manipulation, superficial heat, exercise therapy, interdisciplinary rehabilitation, and cognitive behavior therapy.8 For chronic LBP, the ACP/APS guideline recommends acupuncture, exercise therapy, massage therapy, viniyoga-style yoga, progressive relaxation, spinal manipulation, and interdisciplinary rehabilitation.8 There is conflicting evidence with regard to the efficacy of epidural steroid injections for LBP, and prolotherapy has been found to be effective for pain relief only when combined with a structured physical-therapy regimen.12

Fibromyalgia A diagnosis of exclusion, fibromyalgia occurs in 2%-5% of the population (mostly women).13 No common laboratory tests are confirmatory, so the patient report is the basis for diagnosis. Substance P, a pain-facilitating agent, is found at levels three to five times normal in the cerebrospinal fluid of fibromyalgia patients. Nerve growth factor, which can affect sensory processing, is also elevated in these patients.14 Deficits in serotonin, norepinephrine, and dopamine have also been found. These deficits are thought to account for some of the depressive symptoms associated with fibromyalgia.

Treatment of fibromyalgia is made difficult by the range of symptoms, e.g., painful tender points on the body, sleep disturbance, fatigue, mood disturbances, cognitive loss, restless legs, temporomandibular joint pain, irritable bowel/bladder, anxiety, depression, and panic attacks.13 Recommended treatment options include amitriptyline, cyclobenzaprine, cardiovascular exercise, cognitive behavior therapy, patient education, and multidisciplinary therapy. Opioids are not recommended for long-term treatment. Recently, both pregabalin (Lyrica) and duloxetine (Cymbalta) have been approved by the FDA for treating fibromylagia.

Neuropathic pain The International Association for the Study of Pain defines neuropathic pain as pain initiated or caused by a primary lesion or dysfunction in the nervous system (peripheral or central) that disrupts impulse transmission and modulation of sensory input.15 More simply, neuropathic pain is pain that has no stopping mechanism and can be self-generating once the stimulus is established.

Neuropathic pain is also caused and sustained by an inflammatory response. Once initiated, the human body responds by activating pain facilitators (e.g., bradykinin, substance P, hydrogen ions, interleukin-1beta, nerve growth factor, prostaglandins, histamine, adenosine triphosphate, and tumor necrosis factor).16 When this heightened inflammatory response is triggered, primary and secondary sodium channels are activated, causing neuronal hyperexcitability that is connected to pain production.

The words and phrases used to describe the pain and its presentation can indicate neuropathic pain. Such terms as “burning,” “painful tingling,” “pins and needles,” “strange sensations,” “shooting,” or “feels like electricity” point to some type of nerve damage. Patients may also complain of cold sensitivity. There can be swelling, hair loss, and skin changes in the affected area. Touch or movement may set off abnormally high levels of pain.

Treatment recommendations for neuropathic pain do not include opioids as a first-line option unless pain is severe. Instead, try the following: tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine); selective serotonin and norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine)17; calcium channel alpha2; ligand drugs (e.g., gabapentin, pregabalin)18; and targeted topical analgesics (e.g., 5% lidocaine patch) used alone or in combination with other medications.19

Opioids are considered second-line medications that should be used when needed for pain flares, cancer-related pain, or at initial onset if pain is severe.20

Such nonpharmacologic therapies as relaxation, cognitive behavior therapy, and interventional options may also be helpful.

Neuropathic pain syndromes with specific treatment options include three involving the peripheral nervous system (postherpetic neuralgia, postmastectomy syndrome, and diabetic neuralgia) and CRPS types I and II, which affect the central nervous system.

•    Postherpetic neuralgia occurs most commonly in patients older than age 50 who have shingles, the reactivation of the varicella-zoster virus that is present on peripheral neurons. These neurons become hypersensitive to touch, and the pain is severe. The distribution of the rash is quite distinctive, as
it is found only in the dermatomal distribution of the affected neuron.

•    Postmastectomy pain syndrome develops in approximately 20% of women who undergo lumpectomy or mastectomy with node dissection. The syndrome is more common in younger women and those who are overweight. Patients will likely complain of the typical burning pain in the axilla and chest on the affected side, but they may also complain of “strange painful sensations” or “painful pins and needles.” 21 The pain is sustained by continued inflammatory response in the surgical area. Without early intervention, patients may be unable to fully rehabilitate the surgical-side arm. To avoid functional limitations, targeted topical analgesics, a neuropathic pain medication (e.g., gabapentin), and a short course of opioids will help manage the pain well enough to allow participation in physical therapy.

•    Painful diabetic neuropathy occurs in 37%-45% of type 2 diabetes patients and 54%-59% of type 1 patients.17 Sufferers report allodynia (perception of pain caused by normally nonpainful stimulus) as well as sharp, stabbing, burning pain coupled with numbness (most commonly in the feet). Treatment options include the targeted topical analgesics18 as well as the recommended oral medication regimen from the neuropathic pain guideline.20

•    CRPS type I is a centrally mediated pain syndrome (formerly known as reflex sympathetic dystrophy) with no obvious nerve lesion. In contrast, type II has a detectable nerve lesion. CRPS can develop after surgery, a crush injury, or undertreated acute pain. Transmission moves from peripheral pain stimulus-response to a centrally mediated response that is not governed by the continued peripheral pain input, which makes the syndrome difficult to treat. The syndrome is characterized by sensitivity to heat/cold, hyperalgesia, abnormal swelling, muscle contractures, and high levels of pain for extended periods of time. Treatment can involve a multidisciplinary approach using neuropathic pain medications, physical therapy, and such interventional options as localized blocks.