Paul J. Christo

Cancer pain and analgesia.

Pain ranges in prevalence from 14–100% among cancer patients and occurs in 50–70% of those in active treatment. Cancer pain may result from direct invasion of tumor into nerves, bones, soft tissue, ligaments, and fascia, and may induce visceral pain through distension and obstruction. Cancer pain is multifaceted. Clinicians may describe cancer pain as acute, chronic, nociceptive (somatic), visceral, or neuropathic. Despite implementation of the WHO guidelines, reports of undertreatment of cancer pain persist in various clinical settings and in spite of decades of work to reduce unnecessary discomfort. Substantial obstacles to adequate pain relief with opioids include specific concerns of patients themselves, their family members, physicians, nurses, and the healthcare system. The WHO analgesic ladder serves as the mainstay of treatment for the relief of cancer pain in concert with tumoricidal, surgical, interventional, radiotherapeutic, psychological, and rehabilitative modalities. This multidimensional approach offers the greatest potential for maximizing analgesia and minimizing adverse effects. Primary therapies are directed at the source of the cancer pain and may enhance a patients function, longevity, and comfort. Adjuvant therapies include nonopioids that confer analgesic effects in certain medical conditions but primarily treat conditions that do not involve pain. Nonopioid medications (over‐the‐counter agents) are useful in the management of mild to moderate pain, and their continuation through step 3 of the WHO ladder is an option after weighing a drugs risks and benefits in individual patients. Symptomatic treatment of severe cancer pain should begin with an opioid, regardless of the mechanism of the pain. They are very effective analgesics, titrate easily, and offer a favorable risk/benefit ratio. Cancer pain remains inadequately controlled despite the diagnostic and therapeutic means of ensuring that patients feel comfortable during their illness. Therefore, all practitioners need to make control of cancer pain a professional duty, even if they can only use the most basic and least expensive analgesic medications, such as morphine, codeine, and acetaminophen, to reduce human suffering.

Clinical predictors of success and failure for lumbar facet radiofrequency denervation.

ObjectiveTo determine the clinical factors associated with the success and failure of radiofrequency denervation of the lumbar facet joints. MethodsClinical data were garnered from 3 academic medical centers on 192 patients with low back pain who underwent radiofrequency denervation after a positive response to diagnostic blocks. Success was defined as ≥50% pain relief lasting at least 6 months. Factors evaluated for their association with outcome included duration of pain, opioid use, symptom location, paraspinal tenderness, pain exacerbated by extension/rotation (ie, facet loading), MRI abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery and levels treated. ResultsThe only factor associated with a successful outcome was paraspinal tenderness. Variables that correlated with treatment failure were ‘facet loading,’ long duration of pain, and previous back surgery. ConclusionsIt is counterproductive to use ‘facet loading’ as the sole basis for choosing patients for facet interventions. In patients at high risk for treatment failure, taking additional steps to reduce the rate of false-positive screening blocks may improve outcomes.

Pain management in trauma patients

Cohen SP, Christo PJ, Moroz L: Pain management in trauma patients. Am J Phys Med Rehabil 2004;83:142–161.Trauma is a major cause of mortality throughout the world. In recent years, major advances have been made in the management of trauma, the end result of which has been reduced mortality and enhanced function. One of these areas is pain control. Improved pain management has not only led to increased comfort in trauma patients, but has also been shown to reduce morbidity and improve long-term outcomes. This review focuses on the treatment of pain in the setting of acute injury and on pain management in trauma patients who go on to develop chronic pain. Emphasis is placed on pharmacologic interventions, invasive and noninvasive pain management techniques, analgesia in challenging patients, and pain control in commonly encountered trauma conditions.

Interventional pain treatments for cancer pain.

Cancer pain is prevalent and often multifactorial. For a segment of the cancer pain population, pain control remains inadequate despite full compliance with the WHO analgesic guidelines including use of co‐analgesics. The failure to obtain acceptable pain or symptom relief prompted the inclusion of a fourth step to the WHO analgesic ladder, which includes advanced interventional approaches. Interventional pain‐relieving therapies can be indispensable allies in the quest for pain reduction among cancer patients suffering from refractory pain. There are a variety of techniques used by interventional pain physicians, which may be grossly divided into modalities affecting the spinal canal (e.g., intrathecal or epidural space), called neuraxial techniques and those that target individual nerves or nerve bundles, termed neurolytic techniques. An array of intrathecal medications are infused into the cerebrospinal fluid in an attempt to relieve refractory cancer pain, reduce disabling adverse effects of systemic analgesics, and promote a higher quality of life. These intrathecal medications include opioids, local anesthetics, clonidine, and ziconotide. Intrathecal and epidural infusions can serve as useful methods of delivering analgesics quickly and safely. Spinal delivery of drugs for the treatment of chronic pain by means of an implantable drug delivery system (IDDS) began in the 1980s. Both intrathecal and epidural neurolysis can be effective in managing intractable cancer‐related pain. There are several sites for neurolytic blockade of the sympathetic nervous system for the treatment of cancer pain. The more common sites include the celiac plexus, superior hypogastric plexus, and ganglion impar. Today, interventional pain‐relieving approaches should be considered a critical component of a multifaceted therapeutic program of cancer pain relief.

Post-herpetic neuralgia in older adults: evidence-based approaches to clinical management.

Many individuals across the globe have been exposed to the varicella-zoster virus (VZV) that causes chickenpox. After chickenpox has resolved, the virus remains latent in the dorsal root ganglia where it can re-emerge later in life as herpes zoster, otherwise known as shingles. Herpes zoster is a transient disease characterised by a dermatomal rash that is usually associated with significant pain. Post-herpetic neuralgia (PHN) is the term used for the condition that exists if the pain persists after the rash has resolved. Advanced age and compromised cell-mediated immunity are significant risk factors for reactivation of herpes zoster and the subsequent development of PHN. Though the pathophysiology of PHN is unclear, studies suggest peripheral and central demyelination as well as neuronal destruction are involved.Both the vaccine against VZV (Varivax®) and the newly released vaccine against herpes zoster (Zostavax®) may lead to substantial reductions in morbidity from herpes zoster and PHN. In addition, current evidence suggests that multiple medications are effective in reducing the pain associated with PHN. These include tricyclic antidepressants, antiepileptics, Opioids, NMDA receptor antagonists as well as topical lidocaine (lignocaine) and capsaicin. Reasonable evidence supports the use of intrathecal corticosteroids, but the potential for neurological sequelae should prompt caution with their application. Epidural corticosteroids have not been shown to provide effective analgesia for PHN. Sympathetic blockade may assist in treating the pain of herpes zoster or PHN. For intractable PHN pain, practitioners have performed delicate surgeries and attempted novel therapies. Although such therapies may help reduce pain, they have been associated with disappointing results, with up to 50% of patients failing to receive acceptable pain relief. Hence, it is likely that the most effective future treatment for this disease will focus on prevention of VZV infection and immunisation against herpes zoster infection with a novel vaccine.

The effect of opioid dose and treatment duration on the perception of a painful standardized clinical stimulus.

Background and Objectives: The concept of opioid‐induced hyperalgesia has recently gained prominence as a contributing factor for opioid tolerance and long‐term treatment failure. But whereas the preclinical data for this phenomenon are strong, the mixed clinical data derive primarily from experimental pain models conducted in volunteers and heroin addicts, and nonstandardized clinical stimuli, e.g., surgery. The primary objective of this study is to delineate the effect of opioid dose and treatment duration on pain intensity and unpleasantness ratings following a standardized clinical pain stimulus. Methods: Three hundred and fifty‐five patients, on a steady regimen of analgesic medications and scheduled for an interventional procedure, received a standardized subcutaneous injection of lidocaine prior to a full dose of local anesthetic. Before and immediately following the injection, subjects were asked to rate pain and unpleasantness intensity on a 0 to 10 numerical rating scale. Subjects were stratified into 6 groups based on opioid dosage. A control group of 27 volunteers who had no pain and were taking no analgesics were also injected. Results: Both opioid dose and duration of treatment directly correlated with pain intensity and unpleasantness scores. Baseline pain intensity was also positively associated with both outcome variables. Gender was found to be associated with pain intensity and unpleasantness, with females scoring higher in both categories than males. Compared with patients not receiving opioid treatment, patients receiving opioid therapy were more likely to rate the standardized pain stimulus as being more unpleasant than painful. Conclusions: The results of this study bolster preclinical and experimental pain models demonstrating enhanced pain perception in subjects receiving opioid therapy. This simple clinical model may provide a useful tool in examining opioid‐induced hyperalgesia.

Recommendations for Urine Drug Monitoring as a Component of Opioid Therapy in the Treatment of Chronic Pain

OBJECTIVE Several prominent guidelines recommend that patients on long-term opioid therapy have periodic urine drug monitoring (UDM) for appropriate use; however, none address the specific questions of which patients to test, which substances to test for, how often to test, and how to act on the results. DESIGN In the absence of adequate scientific evidence in the literature, a panel of experts in the field of pain and addiction medicine was convened to develop consensus UDM recommendations. The panel met three times between March 2010 and April 2011, and reviewed several drafts of the recommendations document between meetings. RESULTS The group was able to achieve consensus on a set of UDM recommendations addressing test selection, test frequency, interpretation of results, and how to handle discrepancies based on specific results. CONCLUSION While the participating panel members recognize that there currently is a limited evidence base to support the expert panels recommendations, primary care providers and pain specialists are largely acting today based on anecdote, intuition, and individual experience. The recommendations are meant to begin to provide a framework for standardizing practices for UDM in the treatment of chronic pain, and to serve as a catalyst to advance research that quantifies the effects of UDM on opioid therapy management and patient outcomes.

Opioid effectiveness and side effects in chronic pain

Opioids can provide effective analgesia by way of different routes of administration without limiting side effects for most patients suffering from chronic pain when clinicians properly manage the pertinent patient-, pain-, and drug-centered characteristics. Randomized, placebo-controlled, prospective studies are needed to establish a causal relationship between opioids and hypogonadism. Many of the current studies are retrospective, which only lead to suggestive associations between opioids and hypogonadism and incorporate bias. Clinicians may incorporate available tools, including urine toxicology tests, to assess any aberrant behavior on the part of patients using opioids and to maximize compliance with an opioid regimen.

Single CT-guided chemodenervation of the anterior scalene muscle with botulinum toxin for neurogenic thoracic outlet syndrome.

OBJECTIVE To examine pain relief in patients with neurogenic thoracic outlet syndrome (NTOS) after a single, low dose injection of botulinum toxin A (Botox) into the anterior scalene muscle (ASM) under computed tomographic (CT) guidance. DESIGN Prospective longitudinal study. SETTING Academic medical institution. PATIENTS Patients 18 years of age and older were evaluated for potential scalenectomy and first rib resection using the transaxillary approach at the study institution between 2005 and 2008. All patients had failed physical therapy. A total of 29 procedures on 27 participants were studied. INTERVENTIONS A single, 20-unit injection of Botox into the ASM under CT-guidance. OUTCOME MEASURES Short-form McGill Pain Questionnaire (SF-MPQ) prior to and at 1, 2, and 3 months post-Botox toxin injection. RESULTS There was a decline in pain during the 3 months subsequent to Botox injection as noted by the following components of the SF-MPQ: sensory (P = 0.02), total (P = 0.05), visual analog scale (VAS [P = 0.04]), and present pain intensity (PPI) score (P = 0.06). The proportion of patients reporting more intense pain scores did not return to the pre-intervention level at 3 months post-Botox injection. CONCLUSION Patients experienced substantial pain relief in months 1 and 2 following a single Botox injection into the ASM under CT guidance. Significant pain reduction was noted for 3 months after Botox injection with respect to both sensory and VAS scores, and the total and PPI scores approximated statistical significance. After 3 months, patients experienced a 29% decrease in the sensory component of their pain as well as an approximate 15% reduction in their VAS score. A single, CT-guided Botox injection into the ASM may offer an effective, minimally invasive treatment for NTOS.

The Effect of Morphine on Glial Cells as a Potential Therapeutic Target for Pharmacological Development of Analgesic Drugs

Opioids have played a critical role in achieving pain relief in both modern and ancient medicine. Yet, their clinical use can be limited secondary to unwanted side effects such as tolerance, dependence, reward, and behavioral changes. Identification of glial-mediated mechanisms inducing opioid side effects include cytokine receptors, κ-opioid receptors, N-methyl-D-aspartate receptors, and the recently elucidated Toll-like receptors. Newer agents targeting these receptors such as AV411, MK-801, AV333, and SLC022, and older agents used outside the United States or for other disease conditions, such as minocycline, pentoxifylline, and UV50488H, all show varied but promising profiles for providing significant relief from opioid side effects, while simultaneously potentiating opioid analgesia.