There is widespread consensus that opioid therapy is the mainstay approach for the treatment of moderate-to-severe acute pain, and moderateto- severe chronic pain associated with cancer or AIDS. As noted previously, undertreatment is common despite this consensus, and chemically dependent patients are more likely to be undertreated than those without this history. Although a history of addiction and MMT for addiction may yield challenges during opioid therapy for pain, there is clinical agreement that opioid drugs should still be considered the major approach in these settings.

The role of long-term opioid therapy for noncancer-related pain is evolving rapidly. There are now consensus statements from major professional societies, including the American Society of Addiction Medicine, that acknowledge the appropriateness of this treatment for selected patients. Although the use of this therapy for those with a history of chemical dependency has barely been studied, it is clear from a clinical perspective that, when opioids are required to relieve significant and persistent chronic pain in this population, they must be utilized with appropriate care and structure to avoid complications of use.

Careful assessment must be done when opioid therapy of chronic pain is contemplated for individuals with addictions, in order to clarify the state of the addictive disorder (active, at risk or recovering); to determine the presence or absence of co-morbid psychopathology; to assess the degree to which unrelieved pain may be driving aberrant drug-related behaviors; and to establish a means to structure treatment in a way that would reduce the risk of inappropriate use. The active abuser may be very different from the patient in MMT or in stable drug-free recovery, and the decision to consider long term opioid therapy for chronic pain in these patients presumably carries very different degrees of risk.

When deciding whether to consider long-term opioid therapy for chronic pain in patients with a history of chemical dependency, the clinician should also recognize the difficulties that the patient may experience because of anxiety about relapse, abandonment by friends, or challenges from addiction treatment programs. In all cases, the treatment requires a detailed assessment, including an open discussion with the patient, concerning all risks and benefits.

Many patients who are receiving MMT for addiction recognize that pain is often inappropriately managed in patients on MMT, and this may cause significant anxiety among those confronting injury, illness or surgery. Patients often fear ineffectively treated pain, loss of effective maintenance therapy, and the emergence of acute withdrawal, as well as the possibility of disrespectful treatment by health-care personnel. Anxiety related to these fears may in turn result in behaviors that become challenging to clinicians.

Reassuring the patient that pain management is a high priority, including the patient in decision making, and adhering to good basic principles of pain management are critical to providing effective pain treatment. MMT patients may also experience anxiety about using opioid medications for pain. Some believe they should "grin and bear" their pain because of concern that taking an opioid analgesic constitutes a relapse and will lead to readdiction (15).

These patients and their families and physicians often need reassurance and encouragement to accept the analgesic treatment. It is sometimes helpful to point out that medications prescribed for acute pain are most often time limited and that relief of pain is essential for a quick and healthy recovery. Many former illicit drug users fear losing control over medications and thus refuse any analgesia. Methadone patients receiving a blockade dose can be reassured that their daily dose of methadone will generally block any euphoric effects of the analgesic medications and that analgesics will only produce relief of pain.

However, in some patients, pain may eventually overcome this fear, and a request for pain medication may be made. Some methadone patients fear that use of analgesic opioids will result in the need to increase their maintenance dose of methadone. It has been documented, however, that use of opioids for analgesia does not result in increased dose requirement for maintenance therapy once acute pain is resolved (16). With treatment, methadone patients will most likely continue with their usual maintenance treatment.

In order for pain management to be effective, patients who require maintenance therapy of addiction must be on an effective dose of methadone for their addiction treatment. Patients receiving subtherapeutic doses, who are experiencing early symptoms of withdrawal or craving, will be much more difficult, or impossible, to treat for pain. It may be difficult for patients on subtherapeutic doses to distinguish between the pain from surgical procedures and the pain from withdrawal syndrome. Opioid blockade may reduce the risk of euphorigenic effects and provide relative protection against re-addiction and relapse associated with the therapeutic use of an opioid analgesic.

A study by Compton et al. (17), which examined pain, pain thresholds and pain tolerance in the presence of experimentally induced cold-pressor pain in humans, demonstrated that stable doses of methadone used as maintenance therapy appear to provide no analgesic effect and that methadone maintenance patients overall have lowered pain thresholds (increased pain sensitivity) and less pain tolerance than non-maintained individuals. This research affirms that the usual dose of methadone used chronically for opioid therapy of addiction does not relieve pain and that individuals receiving MMT for addiction may require more aggressive pain management because of a predisposition to pain. If opioid analgesia is selected for the MMT patient, relatively high doses may be needed, both to overcome whatever level of analgesic tolerance the MMT has produced and to address the predisposition to pain (17).

Studies suggest that 30 - 80% of substance abusers suffer from co-existing psychiatric illness (14). Anxiety, panic disorder, and the range of mood disorders (depressive and bipolar) which have a high prevalence in the addiction population may all be associated with bodily discomfort, pain itself, or distorted somatic perception (14). Psychiatric evaluation and effective treatment can be crucial to relieving the pain syndromes in many of these people.

Unless there is compelling evidence suggesting otherwise, all patients presenting with complaints of pain, including those with addictive disorders, should be evaluated and treated for their presenting pain complaint. Most often, individuals seeking opioids for non-medical uses will declare themselves eventually, through a pattern of aberrant behaviors. If opioid therapy is selected as an intervention for pain in the patient with addictive disease, it is important to establish a clear understanding with the patient. Appropriate discussion and documentatio of the potential risks and benefits of therapy, as well as the structural guidelines of treatment, should be made. If therapy takes place in the ambulatory setting and is expected to continue for a prolonged period of time, it may be helpful to detail this understanding in the medical record and have it signed by both treatment provider and patient. This is often referred to as a "contract," agreement, or covenant (18). A number of structural supports may facilitate effective pain therapy in patients with addictive disorders and should be noted in any agreement between patient and provider. These are discussed below.

In the ambulatory setting, it is best for the patient to have one physician prescribe all the analgesics and, preferably, all controlled medications. This provides continuity of care, eliminates overlap of medications, reduces the risk of drug interactions, and is reassuring to both the patient and the clinicians. In this arrangement, the physician prescribing analgesic medications should inform other doctors who are prescribing for the patient, including the methadone prescriber, primary care physicians and any consultants who see the patient on a regular basis.

For those patients in MMT for addiction, it is essential that their team of counselors, nurses and others participate in the evaluation and treatmentplanning process. The treatment staff must know what medications the patient is prescribed in order to observe for effects and side effects, be aware of potential drug interactions, and support the individual in his or her recovery.

Some MMT patients who are receiving opioids for chronic pain choose to drop out of their formal MMT program. Although using the opioid for pain may continue to block craving, the physician prescribing the drug for pain must carefully document that the intention of therapy is analgesic and not addiction management. A decision to leave the MMT program should be carefully discussed with the patient and members of the treatment team. It may be convenient, but such a decision may eliminate an important source of support for the patient.

Opioid analgesics should be titrated according to reported pain, as with all patients reporting pain. Use of pain scales such as a numeric pain scale (0 - 10) or a visual analogue is recommended in order to evaluate both pain and responses to pain treatment. Because of relative tolerance to opioids and possibly lowered pain thresholds, MMT patients often will require higher-than-standard analgesic doses given at more frequent intervals. This must be established with clinical observations (17).

Although methadone is an effective analgesic, it is generally preferred to select an alternative mu agonist opioid such as morphine, hydromorphone or oxycodone, to provide analgesia in methadone-maintained patients. This allows clear distinction between treatment of addiction and treatment of pain, and lessens possible confusion over clinical issues of pain and addiction. In addition, because of its relatively slow onset of action and long half-life, methadone may be difficult to titrate rapidly enough to meet acute pain needs.

A fixed schedule is preferable to a variable "prn" schedule. For an inpatient, this avoids the request for opioids, which may be interpreted by some staff as pathologic drug-seeking behavior, rather than the seeking of pain relief. For ambulatory patients, it avoids the situation where the individual with an addictive disorder has to make a decision as to whether or not to take a potentially rewarding or reinforcing drug based on subjective pain level, a situation which may cause confusion, distress or, possibly, an escalating pattern of pain and medication use. If only intermittent analgesia on an irregular basis is required, it is helpful, when possible, to link doses with activity or time, rather than increased pain alone, in order to avoid the potentially reinforcing effects of opioids on pain perception. In the case of the ambulatory MMT patient requiring additional opioids for analgesia, therefore, treatment may consist of a single methadone dose per day as addiction therapy, plus a fixed schedule of the opioid as used for pain. It is important to be aware that individuals on methadone maintenance therapy of addiction and those using opioids chronically for analgesic pur420 poses will often require relatively high doses of opioids at relatively short intervals, due to tolerance.

A patient using methadone or other mu agonist opioids on a regular basis must avoid the use of opioids with agonist-antagonist properties, such as butorphanol (Stadol®), pentazocine (Talwin ®), nalbuphine (Nubain®), and dezocine (Dalgan ®). Such drugs provide analgesia through activity at non-mu opioid receptors, but act as antagonists at the mu receptor, thus reversing the actions of methadone or other therapeutic mu agonist opioids. Therefore, they may precipitate an acute withdrawal syndrome in patients using mu agonist medications such as methadone (16).

Because individuals on MMT may be relatively tolerant to the effects of opioids, thus requiring high-dose therapy, meperidine and propoxyphene should not be used when prolonged or high-dose analgesia is anticipated. Normeperidine, a metabolite of meperidine, and norpropoxyphene, are potentially neurotoxic agents that may accumulate in such circumstances, causing tremors, agitation and even seizures in some cases. Meperidine is also very short acting, is poorly absorbed after oral administration, and provides only transient analgesia. It has few indications in the treatment of pain.

Only the opioid analgesic may need to be used in higher doses for the methadone patient, unless the patient has developed tolerance to nonopioid substances. For example, an MMT patient with concurrent alcoholism also may have developed tolerance to sedative-hypnotics. Another approach is that offered by anesthesiologists, such as nerve blocks and intraspinal infusion. There are numerous non-medication approaches to pain treatment, beyond the scope of this paper, which may be helpful in individuals on MMT. These include psychological (e.g., cognitive, behavioral and other therapies) and physical modalities (e.g., physical therapy, analgesic modalities such as cold or heat, and neurostimulatory modalities such as transcutaneous electrical nerve stimulation, acupuncture and dorsal column stimulation).