Clinical Guide > Neuropsychiatric Disorders > Pain

Pain Syndrome and Peripheral Neuropathy

January 2011

Chapter Contents


The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage." Pain is subjective, it is whatever patient says it is, and it exists whenever the patient says it does. Pain is a common symptom in people with HIV infection, especially those with advanced disease. It occurs in 30-60% of HIV/AIDS patients and can diminish their quality of life significantly. Like cancer patients, HIV patients experience an average of 2.5 to 3 types of pain at once. Pain in HIV-infected patients may have many causes (as discussed below).

Peripheral Neuropathy

Pain from HIV-associated peripheral neuropathy is particularly common, and may be debilitating. Peripheral neuropathy is clinically present in approximately 30% of HIV-infected individuals and typically presents as distal sensory polyneuropathy (DSP). It may be related to HIV itself (especially at CD4 counts of <200 cells/µL), to medication toxicity (e.g., from certain nucleoside analogues such as stavudine or didanosine), or to the effects of chronic illnesses (e.g., diabetes mellitus). Patients with peripheral neuropathy may complain of numbness or burning, a pins-and-needles sensation, shooting or lancinating pain, and a sensation that their shoes are too tight or their feet are swollen. These symptoms typically begin in the feet and progress upward; the hands may be affected. Patients may develop difficulty walking because of discomfort, or because they have difficulty feeling their feet on the ground. Factors associated with increased risk of peripheral neuropathy include the following:

Patients should be assessed carefully before the introduction of a potentially neurotoxic medication (including stavudine or didanosine), and the use of these medications for patients at high risk of developing peripheral neuropathy should be avoided.

Pain is significantly undertreated, especially among HIV-infected women, because of factors ranging from providers' lack of knowledge about the diagnosis and treatment of pain to patients' fear of addiction to analgesic medications. Pain, as the so-called fifth vital sign, should be assessed at every patient visit.

S: Subjective

Self-report is the most reliable method to assess pain.

The patient complains of pain. The site and character of the pain will vary with the underlying cause. Ascertain the following from the patient:

Measuring the severity of the pain: Have the patient rate the pain severity on a numeric scale of 0-10 (0 = no pain; 10 = worst imaginable pain), a verbal scale (none, small, mild, moderate, or severe), or a pediatric faces pain scale (when verbal or language abilities are absent). Note that pain ratings >3 usually indicate pain that interferes with daily activities. Use the same scale for evaluation of treatment response.

Figure 1. Faces Pain Rating Scale (0-10)

Scale of 1 to 10

Quick screen for peripheral neuropathy: Ask about distal numbness and check Achilles tendon reflexes. Screening for numbness and delayed or absent ankle reflexes has the highest sensitivity and specificity among the clinical evaluation tools for primary care providers. For a validated screening tool, use the ACTG Brief Peripheral Neuropathy Scale (BPNS) to scale and track the degree of peripheral neuropathy.

O: Objective

Measure vital signs (increases in blood pressure, respiratory rate, and heart rate can correlate with pain). Perform a symptom-directed physical examination, including a thorough neurologic and musculoskeletal examination. Look for masses, lesions, and localizing signs. Pay special attention to sensory deficits (check for focality, symmetry, and distribution [such as "stocking-glove"]), muscular weakness, reflexes, and gait. Patients with significant motor weakness or paralysis, especially if progressive over days to weeks, should be evaluated emergently.

To evaluate peripheral neuropathy: Check ankle Achilles tendon reflexes and look for delayed or absent reflexes as signs of peripheral neuropathy. Distal sensory loss often starts with loss of vibratory sensation, followed by loss of temperature sensation, followed by onset of pain. Findings are usually bilateral and symmetric.

A: Assessment

Pain assessment includes determining the type of pain, for example, nociceptive, neuropathic, or muscle spasm pain.

Nociceptive pain occurs as a result of tissue injury (somatic) or activation of nociceptors resulting from stretching, distention, or inflammation of the internal organs of the body. It usually is well localized; may be described as sharp, dull, aching, throbbing, or gnawing in nature; and typically involves bones, joints, and soft tissue.

Neuropathic pain occurs from injury to peripheral nerves or central nervous system structures. Neuropathic pain may be described as burning, shooting, tingling, stabbing, or like a vise or electric shock; it involves the brain, central nervous system, nerve plexuses, nerve roots, or peripheral nerves. It is associated with decreased sensation and hypersensitivity.

Muscle spasm pain can accompany spinal or joint injuries, surgeries, and bedbound patients. It is described as tight, cramping, pulling, and squeezing sensations.

Although pain in HIV-infected patients often results from opportunistic infections, neoplasms, or medication-related neuropathy, it is important to include non-HIV-related causes of pain in a differential diagnosis. Some of these other causes may be more frequent in HIV-infected individuals. A partial list for the differential diagnosis includes:

P: Plan

Perform a diagnostic evaluation based on the suspected causes of pain.


Treatment should be aimed at eliminating the source of pain, if possible. If symptomatic treatment of pain is needed, begin treatment based on the patient's pain rating scale, using the least invasive route. The goal is to achieve optimal patient comfort and functioning (not necessarily zero pain) with minimal medication adverse effects, negotiated with the patient. Use the three-step pain analgesic ladder originally devised by the World Health Organization (WHO); see Figure 2, below.

Nonpharmacologic interventions

The following Interventions can be used at any step in the treatment plan:

Pharmacologic interventions

Principles of pharmacologic pain treatment

The following three steps are adapted from the WHO analgesic ladder. Agents on higher steps are progressively stronger pain relievers but tend to have more adverse effects.

Figure 2. Pharmacologic Approaches to Pain Management: WHO Three-Step Ladder

WHO Pain Ladder

Adapted from World Health Organization. Cancer Pain Relief and Palliative Care, Report of a WHO Expert Committee. Geneva: World Health Organization; 1990.

Note: "Adjuvants" refers either to medications that are coadministered to manage an adverse effect of an opioid or to so-called adjuvant analgesics that are added to enhance analgesia.

Step 1: Nonopiates for mild pain (pain scale 1-3)
Step 2: Mild opiates with or without nonopiates for moderate pain (pain scale 4-6)
Step 3: Opioid agonist drugs for severe pain (pain scale 7-10)
Adjunctive treatments

The addition of antidepressant medications can improve pain management, especially for chronic pain syndromes. These agents, and anticonvulsants, usually are used to treat neuropathic pain (discussed in more detail below), but should be considered for treatment of other chronic pain syndromes as well.

Treatment of neuropathic pain

Assess the underlying etiology, as discussed above, and treat the cause as appropriate. Review the patient's medication list for medications that can cause neuropathic pain. Discontinue the offending agents, if possible. For patients on stavudine or didanosine, in particular, switch to another nucleoside analogue if suitable alternatives exist, or at least consider dosage reduction of stavudine to 30 mg BID (consult with an HIV expert). For patient on isoniazid, ensure that they are taking vitamin B6 (pyridoxine) regularly to avoid isoniazid-related neuropathy.

Nonpharmacologic interventions for neuropathic pain

The nonpharmacologic interventions described above can be useful in treating neuropathic pain.

Pharmacologic interventions for neuropathic pain

Follow the WHO ladder of pain management described above. If Step 1 medications are ineffective, consider adding antidepressants, anticonvulsants, or both before moving on to opioid treatments.


Antidepressant medications often exert analgesic effects at dosages that are lower than those required for antidepressant effects. As with antidepressant effects, optimum analgesic effects may not be achieved until several weeks after starting therapy.


The following agents may be effective for neuropathic pain:

Treatment of Muscle Spasm Pain

Stretching, heat, and massage may help the pain of muscle spasm. This pain also can respond to muscle relaxants such as baclofen, cyclobenzaprine, tizanidine, benzodiazepines, as well as intraspinal infusion of local anesthetics for spinal injuries.

Substance Abuse, HIV, and Pain

Patient Education