Current Perspectives on Pain in AIDS, Part 2

ABSTRACT: As active participants in the care of patients with acquired immunodeficiency syndrome (AIDS), oncologists need to be aware of the many facets of pain management in this population. This two-part article, which began in the June 2002 issue, describes the prevalence and types of pain syndromes encountered in patients with AIDS, and reviews the psychological and functional impact of pain as well as the barriers to adequate pain treatment in this group and others with human immunodeficiency virus (HIV)-related disease. Finally, principles of pain management, with particular emphasis on controlling pain in HIV-infected patients with a history of substance abuse, are outlined. [ONCOLOGY 16:964-982, 2002]

In part 1 of thisarticle, we discussed the prevalence of pain in patients with acquiredimmunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-relateddisease, and offered an overview of pain syndromes in this population. We thenbriefly explored the topics of pain in women and children with AIDS and theimpact of pain on quality of life, before beginning a general discussion on painmanagement in AIDS patients. After assessment and measurement issues, wedetailed three major pharmacotherapeutic approaches—the use of nonopioidanalgesics, opioid analgesics, and adjuvant analgesics. Continuing thediscussion of management, part 2 will address nonpharmacologic interventions,the undertreatment of pain in AIDS patients, and barriers to pain control,concluding with an extensive consideration of pain treatment in HIV-infectedsubstance abusers.

Nonpharmacologic Interventions

A variety of physical and psychological therapies may prove useful in themanagement of HIV-related pain (Table 1). Physical interventions range from bedrest and simple exercise programs to the application of cold packs or heat toaffected sites. Other nonpharmacologic interventions include whirlpool baths,massage, the application of ultrasound, and transcutaneous electrical nervestimulation (TENS). Increasing numbers of AIDS patients have resorted toacupuncture to relieve their pain, with anecdotal reports of efficacy.

Several psychological interventions—including hypnosis, relaxation anddistraction techniques such as biofeedback and imagery, and cognitive-behavioraltechniques—have demonstrated potential efficacy in alleviating HIV-relatedpain. Where nonpharmacologic and standard pharmacologic treatments fail,anesthetic and even neurosurgical procedures (such as nerve block, cordotomy,and epidural delivery of analgesics) are additional options available to thepatient who appreciates the risks and limitations of these procedures.

Undertreatment of Pain in AIDS

Reports of dramatic undertreatment of pain in AIDS patients have appeared inthe literature.[1,2] These studies suggest that all classes of analgesics,particularly opioid analgesics, are underutilized in the treatment of pain inAIDS. Our group[3] has reported that less than 8% of individuals in our cohortof ambulatory AIDS patients reporting pain in the severe range (8-10 on anumerical rating scale of pain intensity) received a strong opioid, such asmorphine, as recommended by published guidelines.[4] In addition, 18% ofpatients with severe pain were prescribed no analgesics whatsoever, 40% wereprescribed a nonopioid analgesic (eg, a nonsteroidal anti-inflammatory drug[NSAID]), and only 22% were prescribed a "weak" opioid (eg,acetaminophen in combination with oxycodone).

Utilizing the Pain Management Index,[5] a measure of adequacy of analgesictherapy derived from the Brief Pain Inventory’s record of pain intensity andstrength of analgesia prescribed, we further examined adequacy of paintreatment. Only 15% of our sample received adequate analgesic therapy, based onthe Pain Management Index. This degree of undermedication of pain in AIDS (85%)far exceeds published reports of 40% undermedication of pain (using the PainManagement Index) in cancer populations. Larue and colleagues[6] found that, inFrance, 57% of patients with HIV disease reporting moderate to severe pain didnot receive any analgesic treatment at all, and only 22% received a weak opioid.

While opioid analgesics are underutilized, it is clear that adjuvantanalgesic agents such as the antidepressants are also dramaticallyunderutilized.[1,2,6,7] Breitbart and colleagues[7] found that less than 10% ofAIDS patients reporting pain received an adjuvant analgesic drug (eg,antidepressants, anticonvulsants), despite the fact that approximately 40% ofthe sample had neuropathic pain. This class of analgesic agents is a criticalcomponent of the World Health Organization (WHO) analgesic ladder, particularlyin managing neuropathic pain, and is vastly underutilized in the management ofHIV-related pain.

Barriers to Pain Management in AIDS

A number of different factors, including patient, clinician, and health-caresystem-related barriers, have been proposed as potential influences on thewidespread undertreatment of pain in AIDS (see Table2).[7-10] Sociodemographicfactors reported to be associated with undertreatment of pain in AIDS includegender, education, and a history of substance abuse.[3] Women, less-educatedpatients, and patients who reported injection drug use as their HIV-transmissionrisk factor are significantly more likely to receive inadequate analgesictherapy for HIV-related pain.

Breitbart and colleagues[9] surveyed 200 ambulatory AIDS patients using amodified version of the Barriers Questionnaire (BQ),[11] which assesses avariety of patient-related barriers to pain management (resulting in patientreluctance to report pain or take opioid analgesics). Results of this studydemonstrated that patient-related barriers (as measured by BQ scores) weresignificantly correlated with undertreatment of pain (as measured by the PainManagement Index) in AIDS patients with pain. Additionally, BQ scores weresignificantly correlated with higher levels of psychological distress anddepression, indicating that patient-related barriers contributed toundertreatment of pain and poorer quality of life.

The most frequently indicated BQ items were those concerning the addictionpotential of opioids, side effects and discomfort related to opioidadministration, and misconceptions about tolerance. Although there were no age,gender, or HIV-transmission risk factor associations with BQ scores, nonwhiteand less-educated patients scored higher on the questionnaire. Examination ofadditional AIDS-specific patient-related barriers[8,9] revealed that 66% ofpatients were trying to limit their overall intake of medications (ie, pills) orutilize nonpharmacologic interventions for pain, 50% of patients could notafford to fill a prescription for analgesics or had no access to painspecialists, and about 50% were reluctant to take opioids for pain because ofconcern that family, friends, or physicians would assume they were misusing orabusing these drugs.

In a survey of approximately 500 AIDS care providers,[10] clinicians(primarily physicians and nurses) rated the barriers to pain management thatthey perceived to be the most important in the care of AIDS patients. The mostfrequently noted barriers were those regarding lack of knowledge about painmanagement or access to pain specialists, and concerns regarding the use andaddiction potential of opioid drugs in the AIDS population. The top fivebarriers indicated by AIDS clinicians were (1) lack of knowledge regardingpain management (51.8%), (2) reluctance to prescribe opioids (51.5%), (3) lackof access to pain specialists (50.9%), (4) concern regarding drug addictionand/or abuse (50.5%), and (5) lack of psychological support/drug treatmentservices (43%).

Patient reluctance to report pain and patient reluctance to take opioids wereless commonly indicated barriers, noted by about 24% of respondents.[10] Incontrast, past surveys of oncologists rated patient reluctance to report pain ortake opioids as two of the top four barriers. Like AIDS care providers,oncologists frequently noted a reluctance to prescribe opioids, even to apopulation of cancer patients with a significantly lower prevalence of past orpresent substance abuse disorders. Both oncologists and AIDS care providersreport that they have inadequate knowledge of pain management and painassessment skills.

Pain Management and Substance Abuse in AIDS

Individuals who inject drugs constitute one of the AIDS exposure categorieswith the highest rates of increase over the past 5 years, especially in largeurban centers. Pain management in the substance-abusing AIDS patient is perhapsthe most challenging of clinical goals. Fears of addiction and concernsregarding drug abuse affect both patient compliance and physician management ofpain (and use of narcotic analgesics), often leading to the undermedication ofHIV-infected patients with pain.

Studies of patterns of chronic narcotic analgesic use in patients withcancer, burns, and postoperative pain, however, have demonstrated that, althoughtolerance and physical dependence commonly occur, addiction (ie, psychologicaldependence and drug abuse) is rare and almost never occurs in individualswithout a history of drug abuse.[12-14] More relevant to the clinical problem ofpain management in AIDS patients, however, is the issue of managing pain in thegrowing segment of HIV-infected patients who have a history of substance abuseor who are actively abusing drugs.

Specifically, the use of opioids for pain control in patients with HIVinfection and a history of substance abuse raises several difficult paintreatment questions. For example: How do we treat pain in people with a hightolerance to narcotic analgesics? How do we mitigate this population’sdrug-seeking and potentially manipulative behavior? How do we deal with patientswho may offer unreliable medical histories or who may not comply with treatmentrecommendations? How do we counter the risk of patients spreading HIV while highand disinhibited.

Patient Credibility

Perhaps of greatest concern to clinicians is the possibility that they arebeing lied to by a substance-abusing AIDS patient complaining of pain.Clinicians must rely on a patient’s subjective report, which is often the bestor only indication of the presence and intensity of pain, as well as the degreeof pain relief achieved by an intervention. Physicians who believe they arebeing manipulated by drug-seeking patients often hesitate to use appropriatelyhigh doses of narcotic analgesics to control pain. They may fear that they arebeing duped into prescribing narcotic analgesics that will be abused or sold.Clinicians do not want to contribute to or help sustain addiction. This leads toan immediate defensiveness on the part of the clinician, an impulse to avoidprescribing opioids, and even an inclination to avoid fully assessing a paincomplaint.

Because concerns are often raised regarding the credibility of AIDS patients’reports of pain, particularly when there is a history of injection drug use,Breitbart and colleagues[15,16] conducted a study of 516 ambulatory AIDSpatients, in which they compared the report of pain experience and the adequacyof pain management among patients with and without a history of substance abuse.They found no significant differences in the report of pain experience (ie, painprevalence, pain intensity, and pain-related functional interference) amongpatients who reported injection drug use as their HIV-transmission risk factorand those who reported other transmission risk factors.

Furthermore, there were no differences in the report of pain experience amongpatients who acknowledged current substance abuse, those in methadonemaintenance, and those who were in drug-free recovery. The description ofHIV-related pain was comparable among both groups. What differed was theirtreatment. Patients in the injection drug use group were significantly moreundermedicated for pain, compared to those with no history of injection druguse.

Martin and colleagues[17] conducted a survey of 211 HIV-infected patients toassess pain reporting in HIV-infected patients with and without intravenous druguse. They demonstrated that non-intravenous drug users showed a strongcorrelation between pain and disease stage, CD4 levels, and mortality rates.Intravenous drug users, however, did not display the same correlations betweenpain and disease parameters. Finally, the investigators concluded that pain wasmore prominent in injection drug users compared to nonusers, suggesting the needto differentiate risk groups in pain-related studies.

Unfortunately, the existence or severity of pain cannot be objectivelyproven. The clinician must accept and respect the patient’s report despite thepossibility of being duped, and proceed in the evaluation, assessment, andmanagement of pain.

Principles of Pain Management in Substance Abusers

Experience from the cancer pain literature suggests that it is possible toadequately manage pain in substance abusers with a life-threatening illness andto do so safely and responsibly using opioid analgesics and sound principles ofpain management, which are outlined in Table 3.[18-20]

Most clinicians experienced in working with this population recommend thatpractitioners set clear and direct limits. While this is an important aspect ofthe care of IV drug-using people with HIV disease, it is by no means the wholeanswer. As much as possible, clinicians should attempt to eliminate the issue ofdrug abuse as an obstacle to pain management by dealing directly with theproblems of opiate withdrawal and drug treatment. Clinicians should err on theside of believing patients when they complain of pain, and should utilizeknowledge of specific HIV-related pain syndromes to corroborate the report of apatient perceived as being unreliable.

Messiah and colleagues[21] sought to demonstrate whether physicians were ableto accurately identify injection drug users and treat them appropriately. Theresults suggest that identification of active users may be partially based onincorrect interpretations of subjective cues.[21

Key Terminology

The clinician must be familiar with and understand thecurrent terminology relevant to substance abuse and addiction. It is importantto distinguish between the terms tolerance, physical dependence, and addictionor abuse.

Tolerance is a pharmacologic property of opioid drugs, defined by the needfor increasing doses to maintain an (analgesic) effect. Physical dependence ischaracterized by the onset of signs and symptoms of withdrawal if narcoticanalgesics are abruptly stopped or a narcotic antagonist is administered.Tolerance usually occurs in association with physical dependence.

Addiction or abuse—also often termed psychological dependence—is apsychological and behavioral syndrome in which there is drug craving, compulsiveuse (despite physical, psychological, or social harm to user), other aberrantdrug-related behaviors, and relapse after abstinence.[22] The termpseudoaddiction has been coined to describe the patient who exhibits behaviorthat clinicians associate with addiction, such as requests for higher doses ofopioid, but in fact is due to uncontrolled pain and inadequate painmanagement.[23]

Addiction Distinctions

The clinician must also distinguish between theformer addict who has been drug-free for years, the addict in a methadonemaintenance program, and the addict who is actively abusing illicit and/orprescription drugs.

Actively using addicts and those on methadone maintenance with pain must beassumed to have some tolerance to opioids and may require higher starting andmaintenance doses of opioids. Preventing withdrawal is an essential first stepin managing pain in this population. In addition, active addicts with AIDS willunderstandably require more in the way of psychosocial support and services toadequately deal with the distress of their pain and illness.

Former addicts may pose the challenge of refusing opioids for pain because offears of relapse. Such patients can be assured that opioids, when prescribed andmonitored responsibly, may be an essential part of pain management, and that theuse of the drug for pain is quite different from its use when they were abusingsimilar drugs.

Defining the Pain Syndrome

Some authorities emphasize the importance ofconducting a comprehensive pain assessment in order to define the pain syndrome.Specific pain syndromes often respond best to specific interventions (eg,neuropathic pains respond well to antidepressants or anticonvulsants). Adequateassessment of the cause of pain is essential in all AIDS patients, andparticularly in the substance abuser. It is critical that adequate analgesia beprovided while diagnostic studies are under way. Often, treatments directed atthe underlying disorder causing pain are very effective as well. For example,headache from central nervous system toxoplasmosis responds well to primarytreatments and steroids.

Pharmacologic Principles

When deciding on an appropriate pharmacologicintervention in the substance abuser, it is advisable to follow the WHOanalgesic ladder. This approach advocates selection of analgesics based onseverity of pain, but clinicians also often take into account the nature of thepain syndrome in selecting analgesics. For mild to moderate pain, NSAIDs areindicated. The NSAIDs are continued with adjuvant analgesics (antidepressants,anticonvulsants, neuroleptics, steroids) if a specific indication exists.Patients with moderate to severe pain and those who do not achieve relief fromNSAIDs are treated with a weak opioid, often in combination with NSAIDs andadjuvant drugs, if indicated.

It is critical that appropriate pharmacologic principles for opioid use areapplied. Data by Kaplan et al[24] suggest that AIDS patients with a priorhistory of drug use benefited from opioid analgesia but required substantiallymore morphine than nonusers. One should avoid using agonist-antagonist opioiddrugs. The use of prn (as-needed) dosing often leads to excessive drug-centeredinteractions with staff that are not productive. While patients should notnecessarily be given the specific drug or route they want, every effort shouldbe made to give patients more a greater sense of control and a sense ofcollaboration with the clinician. Often, a patient’s report of beneficial oradverse effects of a specific agent are useful to the clinician.

Multidimensional Approach

The management of pain in substance-abusingAIDS patients requires a team approach. Early involvement of pain specialists,psychiatric clinicians, and substance abuse specialists is critical.Nonpharmacologic pain interventions should be appropriately applied, not as asubstitute for opioids but as an important adjunct. Realistic goals fortreatment must be set, and problems related to inappropriate behavior around thehandling of prescriptions and interactions with staff should be anticipated.

Hospital staff must be educated and made aware that such difficult patientsevoke feelings that, if acted on, could interfere with providing good care. Theestablishment of clear limits is helpful for both the patient and treatingstaff. Sometimes, written rules about what behaviors are expected and whatbehaviors will not be tolerated (and their consequences) should be provided. Theuse of urine toxicology monitoring, restrictions on visitors, and strict limitson the amount of drug per prescription can all be useful.

Rehabilitation or detoxification from opioids is not appropriate during anacute medical crisis and should not be attempted at that time. Once more stablemedical conditions exist, referral to a drug rehabilitation program may behelpful. The effects of pain interventions must be constantly assessed andreevaluated to optimize care. Special attention should be given to points intreatment when routes of administration are changed or when opioids are beingtapered. It must be made clear to patients what drugs and/or regimen would beintroduced to control pain when opioids are tapered or withdrawn, and whatoptions are available if that nonopioid regimen is ineffective.

Finally, it is important to recognize that substance abusers with AIDS arequite likely to have comorbid psychiatric symptoms as well as multiple otherphysical symptoms that can contribute to increased pain and suffering. For painmanagement to be optimized, adequate attention must be paid to these physicaland psychological symptoms.

Summary

Even in this era of protease inhibitors and decreased AIDS death rates, painis a clinically significant problem in AIDS patients, contributing greatly topsychological and functional morbidity. That said, pain can be adequatelytreated, and so, must be a focus of palliative care in the AIDS patient.Substance abusers and women represent a particularly undertreated segment of theAIDS pain population and require special attention. Managing pain in AIDSpatients with a history of substance abuse is a particularly challengingproblem, which oncologists who provide care to AIDS patients will be facing withincreasing frequency.

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