Tramadol rather than codeine was predominantly used in the "weak" opioid category

Multidisciplinary management of cancer pain: a longitudinal retrospective study on a cohort of end-stage cancer patients.

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About 50% of all cancer patients and 70% of patients with advanced cancer have pain. The World Health Organization (WHO) guidelines for the treatment of cancer pain have proven to be effective in 71%-100% of patients with cancer. To better understand the status of cancer pain management, this study was conducted to evaluate the epidemiology of pain in an end-stage cancer population and assess the effectiveness of multidisciplinary pain management as it is routinely practiced in a cancer center in Taiwan.

A total of 772 patients were identified through the review of medical records from all cancer patients consecutively treated for cancer at the center between January 2001 and June 2003. The study population consisted of all patients who were deceased due to their malignant disease at the time of data collection.

At the inpatient setting, whenever a patient complained of pain or required analgesics, a detailed quantitative assessment of pain would be initiated by his/her nurse and placed in the medical records. Pain intensity was measured using a verbal rating scale 0-10; where 0 = no pain. In the outpatient setting, patients on opioids were evaluated at least every 2 weeks.

All therapies for pain were prescribed essentially by following the WHO guidelines as a much as possible, although opioids such as oxycodone, hydromorphone, and methadone are unavailable in Thailand, making opioid rotation difficult.

Evaluation of outcome of pain treatment was focused on the last 6 months of life. The highest pain intensity on the day of the selected time points, i.e., 6 months, 3 months, 1 month, 1 week, and at the day before death occurred, were analyzed. In this study, substantial pain was defined as pain rated 5 or greater and good and poor pain control corresponded to pain rated 0-4 and 5-10, respectively.

Cancer pain was not restricted to any particular type of cancer; it was present in 80%-96% of cancers. Of 772 patients, 669 (87%) suffered from pain during various time periods, whereas 103 (13%) were free of pain throughout their survival periods. Mean duration of pain was 6.9 months; about half of the data points were between 2 and 9 months. Of the 669 patients with pain, 566 (84%) were caused by primary cancer or metastases; 338 were related to antineoplastic treatments; 93 were due to complications caused by cancer; and 21 had pain unrelated to cancer throughout the course of their disease.

During the last 6 months of life, the prevalence of pain increased at as the survival time shortened, from 20% at 6 months to 79% at one day before death. However, under treatment with the multidisciplinary approach, mild pain or pain-free status could be achieved for most patients. The number of patients having pain scores 5-10 did not exceed 11% during the last 6 months of life.

Tramadol rather than codeine was predominantly used in the "weak" opioid category. Meperidine was briefly used for postoperative pain or following invasive interventions. Patient-controlled analgesia (PCA) and intraspinal analgesia were used in 29% of patients who were considered to have intractable pain. Overall, 79% patients received nonsurgical antineoplastic treatments for pain, including chemotherapy, radiotherapy, and hormonal therapy. Based on the WHO three-step approach, the authors found that 85% of the 669 patients with pain had been treated with "strong" opioids, ranging from a few doses only to long-term for several years. Only 14 patients could obtain sufficient pain relief with nonopioid analgesics alone.

Treatment outcome was measured by pain intensity. Using multidisciplinary pain management, the majority of these patients had their pain become mild to none, and the number with substantial pain ranged from 1% at 6 months to 11% at 1 week pre-death.

In summary, these data revealed that a significant number of patients require an individualized and multidisciplinary approach to achieve adequate pain control, and that the approach resulted in good treatment outcomes. Evaluation of the severity of pain did not show correlation with the progression of cancer or a final crescendo of pain.

Management of peripheral neuropathic pain.

Underlying causes of neuropathic pain include infection, trauma, metabolic abnormalities, chemotherapy, surgery, irradiation, neurotoxins, nerve compression, inflammation, and tumor infiltration. Neuropathic pain syndromes may be divided into two groups, central and peripheral, based on the location of the nervous system lesion.

Available information from experimental animal models suggests that chronic neuropathic pain results from cellular and neuroplastic changes that occur in both the peripheral and central nervous systems. In the periphery, after an event causing nerve damage, an inflammatory response ensues. Lysis of inflammatory cells results in the release of various chemical mediators, including serotonin, bradykinin, substance P, histamine, and other products. If demyelination of the nerve occurs (A-beta or A-delta), ectopic discharges along the length of the nerve fiber may provide sustained afferent input to the spinal cord. These ectopic signals may persist for extended periods of time and are believed to play a role in the initiation and maintenance of neuropathic pain. Continuous discharge in C fibers may produce sensations of burning pain, whereas intermittent spontaneous discharges in A-delta or A-beta fibers may produce lancinating dysesthesias or paresthesias.

Central sensitization, together with peripheral changes, is believed to account for the clinical phenomenon of allodynia. Neuroplasticity refers to the ability of neurons to alter their structure or function. Central sensitization seems to be mediated through the release of various neurotransmitters such as substance P, glutamate, calcitonin gene-related peptide, gamma aminobutyric acid (GABA), and neurokinin A.

Treatment options include anticonvulsants, antidepressants, topical analgesics, opioids, and other drugs. Anticonvulsant drugs act by a variety of different mechanisms, including having effects on sodium or calcium conductance, increases in GABA levels, decreases in glutamate levels, and other unknown mechanisms. The majority of their uses are off label. The drugs are described in this article and include gabapentin, carbamazepine, pregabalin, oxcarbazepine, sodium valproate, topiramate, and zonisamide.

Tricyclic antidepressants (TCAs -- amitriptyline, nortriptyline, imipramine, clomipramine, desipramine, and doxepin) have an analgesic effect independent of their antidepressant effect. TCA-mediated inhibition of reuptake of norepinephrine and serotonin at spinal dorsal horn synapses is well known, and alternative potential mechanisms include blockade of sodium channels, GABAB effects, potassium channel blockade, and effects on adenosine. Currently, none of the TCAs are FDA-approved for use as an analgesic.

Chemical treatments for neuropathic pain include the 5% lidocaine patch, ketamine gel, and capsaicin. Lidocaine, like other local anesthetics, seems to act through inhibition of voltage-gated sodium channels. Capsaicin is thought to elevate the pain threshold in areas to which it is applied through depletion of substance P from the membranes of type C nociceptive fibers. Ketamine gel is an N-methyl-D-aspartate-receptor antagonist. Results with these are varied.

The consensus of clinical opinion on the use of opioids for neuropathic pain is evolving in view of results from several recent, well-controlled trials. Oxycodone, morphine, tramadol, and methadone have shown efficacy for the treatment of this type of pain, particularly following the use of controlled-release oxycodone and morphine. Tramadol works through multiple mechanisms, including mu-opioid receptor agonists, inhibition of serotonin and norepinephrine reuptake, and enhancement of neuronal serotonin release. Methadone was evaluated and demonstrated slightly improved visual analogue scale pain scores in neuropathic pain.

Muscle relaxants are sometimes prescribed. Baclofen, dantrolene, and tizanidine have shown efficacy in treatment of spasticity. Intrathecal baclofen was effective for spasticity-related pain. Options for interventional therapy include peripheral nerve blocks, neuraxial nerve blocks, implanted spinal cord stimulators, and implanted intrathecal catheters. The topic of rational polypharmacy is discussed in the article.

The author concludes that improved understanding of basic science provides an inroad into more rational strategies for pharmacotherapy. Neuropathic pain remains a challenge for the clinician, best addressed by a thorough understanding of newer and older treatment options and the evidence base that supports their use.