| Pain Syndrome and Peripheral NeuropathyJuly 2006; updated July 2007 | Background | | 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 in those with advanced HIV disease.
It occurs in 30-60% of HIV/AIDS patients and can diminish their quality of life
significantly. Like cancer patients, HIV patients experience, on average, 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
<200 cells/µL), to medication toxicity (eg, from certain nucleoside
analogues such as didanosine or stavudine), or to the effects of chronic
illnesses (eg, 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. Factors associated with increased risk of peripheral neuropathy
include the following: | Previous peripheral neuropathy | | | Low CD4 count (<100 cells/µL) | | | Prior AIDS-defining opportunistic infection or neoplasm | | | Vitamin B12 deficiency | | | Concomitant use of other drugs associated with peripheral neuropathy (eg,
isoniazid) | | | Use of neurotoxic agents (eg, alcohol) | |
Patients should be assessed carefully before the introduction of a potentially
neurotoxic nucleoside analogue (eg, didanosine, stavudine) to avoid the use of
these medications in patients at greatest risk of developing peripheral
neuropathy. Pain is significantly undertreated, especially in 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. | |
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| SOAP (Subjective, Objective, Assessment, Plan) | | | Subjective | | The patient complains of pain. The site and character of the pain will vary with the
underlying cause. Ascertain the following from the patient: | | | | Duration, onset, progression | | | Distribution, symmetry | | | Character or quality (eg, burning, sharp, dull) | | | Intensity | | | Severity (see below) | | | Neurologic symptoms (eg, weakness, cranial nerve abnormalities, bowel or
bladder abnormalities) | | | Exacerbating or relieving factors | | | Response to current or past treatments | | | Past medical history (eg, AIDS, diabetes mellitus) | | | Alcohol intake (amount, duration) | | | Medications, current and recent (particularly zalcitabine, didanosine,
stavudine, and isoniazid) | | | Nutrition (vitamin deficiencies) | | | Meaning of the pain to the patient | |
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| Objective | | Measure vital signs (an increase in blood pressure, respiratory rate, and heart rate
can correlate with pain). Perform a symptom-directed physical examination, including
a thorough neurologic 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. | |
| Assessment | | Pain assessment includes determining the type of pain: nociceptive or neuropathic.
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. Nociceptive pain 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. Assess the severity of the pain. Have the patient rate the pain severity on a
numeric scale of 0-10 (0 = no pain and 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. Although pain in HIV-infected patients is often due to 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: | Anorectal carcinoma | | | Aphthous ulcers | | | Appendicitis | | | Arthritis, myalgias | | | Candidiasis, oral or esophageal | | | Cholecystitis | | | Cryptococcal disease | | | Cytomegalovirus colitis | | | Dental abscesses | | | Gastroesophageal reflux disease (GERD) | | | Ectopic pregnancy | | | Herpes simplex | | | Herpes zoster | | | Kaposi sarcoma | | | Lymphoma | | | Medication-induced pain syndromes (eg, due to growth hormone, granulocyte
colony-stimulating factor) | | | Medication-induced peripheral neuropathy (eg, due to didanosine, stavudine,
isoniazid, vincristine) | | | Mycobacterium avium complex | | | Myopathy | | | Other neuropathy | | | Pancreatitis | | | Pelvic inflammatory disease | | | Toxoplasmosis | |
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| Plan | | Perform a diagnostic evaluation based on the suspected causes of pain. | Treatment | | 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 with minimal medication adverse effects.
Use the 3-step pain analgesic ladder originally devised by the World Health
Organization (WHO). | Pharmacologic interventions | | The following 3 steps are adapted from the WHO analgesic ladder. | Step 1: Nonopiates for mild pain (scale 1-3) | | | The most common agents in this step include acetaminophen and
nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2
(COX-2) inhibitors. | | | Acetaminophen has no effect on platelets and no antiinflammatory
properties; avoid use in patients with hepatic insufficiency. | | | Note that COX-2 inhibitors have been associated with an increased
risk of cardiovascular events and should be used with caution. | | | Tramadol (Ultram) is a centrally acting nonopiate that can be
combined with NSAIDs. Avoid coadministration with selective
serotonin reuptake inhibitors (SSRIs) and monoamine oxidase
inhibitors (MAOIs) because of serotonin syndrome; also avoid in
patients with a seizure history. | |
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| Step 2: Mild opiates with or without nonopiates for moderate pain
(scale 4-6) | | | Most agents used to treat moderate pain are combinations of
opioids and Step 1 agents. | | | The most common agents are acetaminophen combined with codeine,
oxycodone, or hydrocodone. | | | Meperidine (Demerol) should be avoided because its active
metabolite, normeperidine, has activating properties that may cause
delirium and seizures. | | | Chronic pain is more likely to be controlled when analgesics are
dosed on a continuous schedule rather than "as
needed." Sustained-release formulations of opioids should
be used whenever possible. | | | For breakthrough pain, use "as needed"
medications in addition to scheduled-dosage analgesics. | |
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| Step 3: Opioid agonist drugs for severe pain (scale 7-10) | | | Morphine is the drug of choice in this step. Others used are
oxycodone, hydromorphone, fentanyl, levorphanol, methadone, codeine,
hydrocodone, oxymorphone, and buprenorphine. | | | Avoid meperidine because of the increased risk of delirium and
seizures. | | | Around-the-clock, oral, sustained-release dosing will achieve
optimum pain relief. Patients unable to take oral therapy may use
transdermal fentanyl patches or rectal administration of
sustained-release tablets. | | | Anticipate and treat complications and adverse effects of opioid
therapy, such as nausea, vomiting, and constipation. | |
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| 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. Consider dosage
reductions of stavudine to reduce peripheral neuropathy (consult with an HIV
expert). For isoniazid regimens, ensure that patients are taking vitamin B6
(pyridoxine) regularly to avoid isoniazid-related neuropathy. | 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. | Anticonvulsants | | The following may be effective for neuropathic pain. | Gabapentin (Neurontin): Starting dosage is 100-300 mg 2 or
3 times daily. Usual maintenance dosage is 1,200-3,600 mg/day in
divided doses. Monitor response and increase the dosage every 1-2
weeks by 300-600 mg/day. Adverse effects include somnolence,
dizziness, fatigue, and nausea. | | | Lamotrigine (Lamictal): Starting dosage is 25 mg twice
daily. Usual maintenance dosage is 50-300 mg/day in divided doses.
Adverse effects include sedation, dizziness, ataxia, confusion,
nausea, blurred vision, and rash. | | | Valproic acid (Depakote): Starting dosage is 500 mg twice
daily. Usual maintenance dosage is 500-1,500 mg 2 or 3 times daily.
Monitor valproic acid serum levels. Adverse effects include weight
gain, sedation, ataxia, nausea, and diarrhea. | | | Although phenytoin and carbamazepine have some effectiveness in
treating neuropathy, they have significant drug interactions with
protease inhibitors and nonnucleoside reverse transcriptase
inhibitors, and their use in HIV-infected patients is limited.
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| Substance Abuse, HIV, and Pain | | Some health care providers hesitate to treat pain in patients with current or
past substance abuse because of concern about worsening these patients'
dependence on opioids or suspicion that such patients are seeking pain
medications for illicit purposes. However, the following points should be
considered: | Many patients with current or past substance abuse do experience pain, and
this pain should be evaluated by care providers and treated appropriately. | | | Failure to distinguish among addiction, tolerance, and dependence can lead
to undertreatment of chronic pain by health care providers. | | | Addiction (substance abuse) is a complex behavioral syndrome characterized
by compulsive drug use for the secondary gain of euphoria. | | | Pharmacologic tolerance refers to the reduction of effectiveness, over
time, of a given dosage of medication. | | | Physical dependence is the consequence of neurophysiologic changes that
take place in the presence of exogenous opioids. | | | Aberrant use of pain medications, if it develops, is best managed by an
interdisciplinary team of providers from HIV clinical care, psychiatry,
psychology, pharmacy, social services, and drug addition management. | | | Drug-drug interactions between certain antiretroviral medications and
methadone can decrease methadone serum concentrations (see chapter
Drug-Drug Interactions with HIV-Related Medications). If this
occurs, methadone dosages may need to be increased to prevent opiate
withdrawal. | | | As part of chronic pain management in patients with substance abuse,
consider establishing a written pain-management contract to be signed by the
clinician and the patient. The contract should: | | | Clearly state limits and expectations for both the patient and provider | | | Identify a single clinician responsible for managing the pain regimen | | | Tell the patient what to do if the pain regimen is not working | | | Describe the procedure for providing prescriptions (eg, 1 prescription
given to the patient, in person, for a limited period of time, such as 1
month). | | | List the rules for dealing with lost medications or prescriptions | |
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| Patient Education | | |
| Pain management is part of HIV treatment and patients should give feedback to
allow the best treatment decisions. If pain persists for more than 24 hours at a
level that interferes with daily life, patients should call so that their health
care provider can change the plan and try additional measures if needed. | | | Patients should not expect full pain relief in most cases, but enough relief
that they can perform their daily activities. | | | "Mild" pain medications (eg, NSAIDs, aspirin, acetaminophen)
usually are continued even after "stronger" medications are
started because their mechanism of action is different from that of opiates.
This combination of pain medication has additive effects, so that pain may be
controllable with a lower narcotic dosage. | | | Patients taking "around the clock" medications, should take
them on schedule. Those taking "as needed" medications should
take them between doses if they have breakthrough pain. | | | Opiates are noted for causing severe constipation. Patients must remain
hydrated and may need stool softeners, laxatives, or other measures. They should
call their health care provider quickly if constipation occurs. | | | Patients should avoid recreational drugs or alcohol when taking opiates
because opiates can interact with them or cause additive adverse effects,
possibly resulting in central nervous system depression, coma, or death. | | | Patients taking opiates should avoid driving and operating machinery. | |
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| References | | | The appearance of external hyperlinks does not constitute endorsement by the Department of Veterans Affairs of the linked Web sites, or the information, products or services contained therein. | | |
| Alexander C. Palliative and End-of-Life Care. In: Anderson JR, ed. A Guide to the Clinical Care of Women with HIV. Rockville, MD: Health Services and Resources Administration; 2005. Available online at hab.hrsa.gov/publications/womencare05/. Accessed May 20, 2006. | | | American Academy of HIV Medicine. Pain Management. The HIV Medicine
Self-Directed Study Guide (2003 ed.). Los Angeles: AAHIVM; 2003. | | | Association of Nurses in AIDS Care. Pain. In: Kirton C, ed. Core Curriculum
for HIV/AIDS Nursing, 2nd ed. Thousand Oaks, CA: Sage Publications;
2003:143-155. | | | Breitbart W. Suicide Risk and Pain in Cancer and AIDS. In: Chapman CR, Foley
KM, eds. Current and Emerging Issues in Cancer Pain: Research and Practice. New
York: Raven Press; 1993:49-66. | | | Hahn K, Arendt G, Braun JS, et al. A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies. J Neurol. 2004 Oct;251(10):1260-6. | | | Singer EJ, Zorilla C, Fahy-Chandon B, et al. Painful symptoms reported by ambulatory HIV-infected men in a longitudinal study. Pain. 1993 Jul;54(1):15-9. | | | Slaughter A, Pasero C, Manworren R. Unacceptable pain levels. Am J Nurs. 2002 May;102(5):75, 77. | | | Swica Y, Breitbart W. Treating pain in patients with AIDS and a history of substance use. West J Med. 2002 Jan;176(1):33-9. | | | U.S. Department of Health and Human Services. Management of Cancer Pain.
Rockville, MD: Department of Health and Human Services; 1994. | | | U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 10, 2006. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7. Accessed July 3, 2007. | | | O'Neill WM, Sherrard JS: Pain in human immunodeficiency virus disease: a review. Pain. 1993 Jul;54(1):3-14. | | | Weinreb NJ, Kinzbrunner BM, Clark M. Pain Management. In: Kinzbrunner BM,
Weinreb NJ, Policzer JS, eds. 20 Common Problems: End-of-life Care. New York:
McGraw Hill Medical Publishing Division; 2002:91-145. | | | World Health Organization. Cancer Pain Relief and Palliative Care, Report of a
WHO Expert Committee. Geneva: World Health Organization; 1990. | |
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