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May-June 2006; Issue 3Strong Opioids Show Better Relief in Chronic Noncancer Pain This edition of News/Research Updates was researched/compiled by Winnie Dawson, MA, RN, BSN, and edited by Stewart B. Leavitt, MA, PhD; Medical reviewers were: Lee A. Kral, PharmD, BCPS; Paul W. Lofholm, PharmD, FACA; James D. Toombs, MD. Posting Date: June 24, 2006. Strong Opioids Show Better Relief in Chronic Noncancer PainA meta-analysis in the May issue of the Canadian Medical Association Journal examined the literature for studies focusing on opioid efficacy, side effects, and risks of abuse or addiction. Data from 41 studies that reported results on a total of 6,019 patients were included in the analysis. All patients had chronic noncancer pain: 80% had nociceptive pain of rheumatoid arthritis, osteoarthritis or back pain without radiculopathy; 12% neuropathic pain; 7% fibromyalgia, and 1% had mixed pain. Treatment duration varied from 1 to 16 weeks (average, 5 weeks) and oral, transdermal, or rectal administration was prescribed for 5 different opioids. Oxycodone and morphine were classified as “strong opioids,” while codeine, tramadol and propoxyphene were considered “weak opioids” in this analysis. Opioids were most favorable in all placebo-controlled studies, except the 1% with mixed pain. In the 8 trials comparing opioid therapy with other analgesic agents (either NSAIDs or tricyclic antidepressants), the results showed no significant statistical differences overall; although, “strong opioids” were significantly more effective for pain relief but not for functional outcomes. Two studies – comparing tramadol versus diclofenac and controlled-release morphine versus nortriptyline – did not result in significant statistical differences for functional outcomes. Two opioid side effects, constipation and nausea, were clinically significant, while diarrhea occurred less often with opioids than other drugs. Dropout rates were 33% and 38% in the opioid and control groups, respectively. Studies on patients with an addiction history were excluded from the analysis and only 3 studies out of 41 questioned participants about symptoms of addiction. In the 1 study that requested answers to specific questions on “drug craving,” approximately 9% in the morphine group and 4% in the placebo group reported the development of a drug craving.Clinical Implications: The investigators caution that many studies on opioids contain weaknesses in terms of study duration, collection of data related to opioid tolerance, and longer-term side effects like sexual function and hypogonadism. In addition, while opioids demonstrate consistent effectiveness when compared with placebo, additional equivalence studies are needed to compare opioids with other analgesic drugs. Source: Furlan AD, Sandoval JA, Mailis-Gagnon A et al. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006(May);174(11):1589-1594. < Back to Top > Update: Pain Management During Methadone MaintenancePatients in methadone maintenance treatment (MMT) for opioid addiction frequently have pain conditions that can present added clinical challenges in pain management. As a further complication, there are many misunderstandings among practitioners regarding effects of methadone during MMT versus when the medication is used for analgesia. An update on these issues in Addiction Treatment Forum (ATForum.com) reviews recent literature and provides the following summary points on managing pain during MMT:
Some research further suggests that opioid-addicted persons may have or develop an abnormally low tolerance for painful stimuli (hyperalgesia). Additionally, long-term daily opioid administration, whether during MMT or to treat chronic pain, may paradoxically increase sensitivity to pain; thus counteracting analgesic effects of opioids. Practice Pointers:The observations regarding methadone in MMT also would apply to buprenorphine, which is approved for the maintenance treatment of opioid addiction. The recent discussions in the literature reinforce 2 important overall principles: (A) methadone or buprenorphine maintenance do not themselves facilitate pain relief in those patients with pain conditions, and (B) the complaints of these patients about increasing pain are probably more real than imagined. Since the analgesic effectiveness of opioids in these patients may be limited, it emphasizes the value of employing additional methods of pain control. Minimally, this might recommend the potential usefulness of switching from one type of opioid analgesic to another when pain seems to get worse rather than better. Healthcare providers need to be aware of these issues to deliver adequate pain management for this patient population. Source: Leavitt S. Perils of pain in MMT: Updated evidence. Addiction Treatment Forum. 2006(Spring);15(2):1,6-7. Available at: http://www.atforum.com/SiteRoot/pages/current_pastissues/spring2006.html#perilsofpain. Access checked 6/20/06. < Back to Top > Random Testing Reduces Illicit-Drug Use in Patients With PainResearchers conducted a study of 500 patients from an interventional pain management practice to investigate the impact of random urine testing for illicit-drug use during opioid treatment for pain. All patients were on stable doses of hydrocodone, oxycodone, methadone, or morphine as supplemental treatment to their primary therapy. Patients were informed that rapid screen drug tests would be performed randomly. Tests were identified as positive if one of the following illicit drugs was present in the screening results: cocaine, marijuana, amphetamines, or methamphetamine. Positive tests for the last 3 drugs were double-checked for possible false-positive results. Overall, illicit drug use in this patient sample was 16%. These results were compared with a previous study of a similar population (Manchikanti et al. 2005) which showed illicit drug use prevalence of 22%.Clinical Implications: The results of this study suggest that random urine drug testing can help reduce the use of illicit drugs in patients receiving opioids for chronic pain management. In terms of abuse based on age, 26% of patients under 45 years of age, 13% of those between 45 and 64 years, and no patients over age 65 were abusers. [In this study, every participant was drug-tested; however, similar reductions in substance abuse might be accomplished via a well-designed program that includes patient education, medication management agreements, and random drug testing primarily in the highest-risk age groups. – W. Dawson, MA, RN, BSN.] Source: Manchikanti L, Manchukonda R, Pampati V, et al. Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids? Pain Physician. 2006(Apr);9(2):123-129. Previous Study Source: Manchikanti L, Fellows B, Damron KS, et al. Prevalence of illicit drug use among individuals with chronic pain in the Commonwealth of Kentucky: an evaluation of patterns and trends. J Ky Med Assoc. 2005(Feb):103(2):55-62. < Back to Top > Pediatric Pain Assessments Need ImprovementAn evaluation was done on a national sample of emergency department (ED) pediatric visits from the National Hospital Ambulatory Medical Care Survey to identify the presence or absence of a documented pain score, the level of pain severity, and the resulting relationship to analgesic use. The sample of patients 18 years of age or younger who visited the ED for pain during a 4-year period totaled 24,707.
Practice Pointers: Surprisingly, only approximately half of the pediatric visits for injuries known to be painful, such as burns and fractures, had recorded pain scores. And, less than 60% of patient records included a pain score for illnesses that are identified by an American Academy of Pediatrics policy statement as recommending a pain assessment. Examples are otitis media, headache, pharyngitis, and pelvic pain. The authors state that pain documentation is clearly suboptimal and an improvement would mean better pain management and better patient outcomes. Source: Drendel AL, Brousseau DC, Gorelick MH. Pain assessment for pediatric patients in the emergency department. Pediatrics. 2006(May);117(5):1511-1518. < Back to Top > Music Helps Reduce Chronic Pain SymptomsThis study compared the effects of daily music listening on the power, pain, disability, and depression of patients with chronic non-malignant pain. The experiences of pain, disability, and depression were each measured using individual assessment tools. One additional measurement was that of “power,” defined in this study as a “knowing participation in change”; for this, a separate instrument was used to measure concepts like choices, freedom, awareness, and personal involvement in creating change. A total of 60 patients who experienced pain for an average of 6.5 years were randomly assigned to a researcher-selected music group, a subject-preferred music group, or to a control group. The participants in the subject-preferred group were asked to make personal selections of music that would help them to relax, reduce anger, improve mood, decrease anxiety, and/or promote energy. It was suggested that they choose instrumental or vocal selections that were upbeat, familiar, and soothing or rhythmic according to their needs and preferences. The researcher-provided music participants were allowed to choose one pre-recorded relaxing instrumental tape offering piano, jazz, orchestra, harp, or synthesized music. Music group participants listened to music 1 hour per day for 7 days. All participants completed pre-intervention questionnaires, kept a diary, and completed a second set of questionnaires on day 9. Both music groups reported more power and less pain, disability, and depression than the control group. Also, in the music groups, pain measures declined by about 20% and depression scores dropped 15% to 23%. Disability scores decreased 4% with subject-preferred music and 13% when the researcher provided the music. An up to 8% increase in power was observed in the music groups. Overall differences between the researcher-provided music and the subject-preferred music were not statistically significant. Two-thirds of the participants who completed the 2nd set of questionnaires responded that the music had been helpful in managing their pain and would continue to use music as a therapeutic tool.Practice Pointers: Music is a safe and inexpensive way for patients to reduce their chronic pain symptoms in a way that also offers an opportunity to exhibit a measure of personal power over their symptoms. Healthcare providers can explore ways to offer music in treatment and rehabilitation settings and to encourage patients to explore their options for music in their home environments. This study did not evaluate the advantages of any specific type of music and the researchers stated that a variety of music styles were found to be effective. Caregivers can aid a patient’s selection of music therapy timing based on the potential for greatest need and, in addition, offer help with music selection according to preferences related to age, culture, and personal enjoyment. Source: Siedliecki SL, Good M. Effects of music on power, pain, depression and disability. 2006(Jun);54(5):553-562. < Back to Top > Ergonomic Forearm Support Reduces Pain of Keyboard UseShoulder and neck pain can be associated with the repetitive strain of computer keyboard use. This controlled trial randomized 182 customer service employees of a large healthcare organization to 1 of 4 interventions designed to reduce upper body pain. The participants followed an intervention for one year and received either: A) ergonomics training only, B) training plus a trackball (a stationary cursor-control device that functions somewhat like an upside-down mouse), C) training plus a forearm support, or D) training plus both a trackball and forearm support. During the year-long intervention, weekly questionnaires were completed to assess the pain in neck, shoulders, and arms. By year-end, more than a third (63) of all participants had been diagnosed with one or more musculoskeletal disorders such as wrist tendonitis, elbow tendonitis, or muscle strain of the neck and upper back. However, the use of a forearm support reduced the risk of shoulder and neck disorders by about half. Additionally, this intervention significantly reduced self-reports of neck and shoulder pain as well as right upper extremity pain when compared with only the ergonomics training. The use of a trackball did not have a significant effect on neck and shoulder disorders but did significantly reduce the risk for left upper extremity disorders; an unexpected result, since almost all subjects operated the mouse or trackball with their right hand.Clinical Implications: This study demonstrates that the risk for upper body musculoskeletal disorders in keyboard users is high but can be dramatically reduced by using a simple device easily found through an Internet search using terms like “forearm support,” “ergonomic arm support,” or “arm board.” These are available in different styles and many attach to the front edge of the desk. Healthcare providers should query patients with upper body chronic pain about their computer use and workplace ergonomics. In addition, the treatment regimen should include patient education and information on the benefits of using forearm supports to reduce pain and discomfort. Source: Rempel DM, Krause N, Goldberg R, et al. A randomized controlled trial evaluating the effects of two workstation interventions on upper body pain and incident musculoskeletal disorders among computer operators. Occup Environ Med. 2006(May);63(5):300-306. < Back to Top > African Americans Use Fewer Migraine Healthcare ServicesIn response to growing concerns about ethnic disparities in pain management, this study compared 131 Caucasian and African American migraine sufferers on several aspects of diagnosis and treatment in a primary care setting. Patients with moderate-to-severe headaches completed questionnaires regarding their headaches and resulting disability, to identify any differences in: A) the utilization of the healthcare system for headache treatment, B) diagnosis and treatment by a physician, C) patient-physician communication and mistrust of the healthcare system, and D) perception of headache triggers. Since additional demographics of the two groups did not differ significantly except for socioeconomic status and group size, the outcome analysis included a control for both. There were no significant differences in frequency, severity and duration of headaches. Results showed that 72% of Caucasians and 46% of African Americans sought physician assistance for headache care. Caucasians were more than twice as likely as African Americans to be under a doctor’s care and almost twice as likely to receive prescription medications for acute headache pain. The African American participants were much less likely to have a physician-patient discussion of behavioral options or to discuss the benefits of managing triggers. They also reported a higher level of mistrust and lower level of patient-physician communication than the Caucasians, which might coincide with the lower utilization of care.Clinical Implications: The investigators state that a low incidence of preventive medications prescribed and the low percentages of behavioral consulting in both groups indicate that inadequate care was received in general. Because ethnic disparities appeared to exist for healthcare utilization, diagnosis, and treatment in moderate-to-severe headache, physicians need to become more aware of cultural differences in communication and pain presentation. The authors further recommend that physicians use evidence-based guidelines for treating all migraine patients. Source: Nicholson RA, Rooney M, Vo K, et al. Migraine care among different ethnicities: do disparities exist? Headache. 2006(May);46(5):754-65. < Back to Top > Occipital Nerve Injection Relieves Primary Headache
Subjects completed a headache diary for one week pre-treatment and one-week post-treatment; an injection-day exam included whether regional tenderness at the great occipital nerve was evident or not. Clinical symptoms determined the precise unilateral injection site to be at or near 1 cm to 2 cm below the midpoint between the occipital tubercle and the mastoid process (see anatomical drawing). A solution of 3 ml of 2% lidocaine and 80 mg of methyl-prednisolone was injected and massaged to spread the analgesic mixture. A total of 116 injections were completed during a 16-month trial period. Efficacy was based on the results of the headache diary and follow-up phone calls to identify complete response, partial response (minimum 30% reduction in severity or frequency), or no response. In total, 53% of injections demonstrated some response, with a complete response in 22% and partial in 31%. The mean duration of response was 20 days for complete responders and 45 days for those experiencing partial relief. Author's Comments: Clinically, it is important to note that greater occipital nerve regional tenderness was significantly associated with a favorable response to treatment and, therefore, suggests which patients are more likely to respond to this injection therapy. For future research, the investigators noted that the duration of pain relief from a local anesthetic exceeded what was expected and they suggest conducting studies against a placebo control. Source: Afridi SK, Shields KG, Bhola R, et al. Greater occipital nerve injection in primary headache syndromes – prolonged effects from a single injection. Pain 2006(May);122(1-2):126-129. < Back to Top > Oxycodone Similar to Morphine in Cancer PainA systematic review of oxycodone in cancer-related pain resulted in the selection of 4 studies comprising this meta-analysis evaluating efficacy and tolerability. The final analysis included 160 patients without any significant differences in pre-intervention pain scores between treatment and control groups. Three studies compared oxycodone with morphine, while the fourth was an oxycodone and hydromorphone comparison study. All 4 studies lasted from 10 to 20 days and resulted in similar outcomes for pain management and tolerability. Although patients who had withdrawn from any study were not included in this analysis, the authors point out that the overall rates of discontinuation and adverse effects were similar to the rates from other studies of opioid use in cancer and non-cancer patient populations. Based on the similarities in analgesic efficacy and adverse effect profiles, this evaluation supports the use of oxycodone in cancer-related pain. Clinical Implications: Studies have shown that about 20% of patients being treated with morphine for pain management may need an alternate opioid because of ineffective pain relief and unacceptable adverse effects. The authors reinforce the need for clinicians to inform patients of the potential for immediate adverse effects, and they suggest early management of these effects along with appropriate dose titration. At least 1 study has suggested that oxycodone may have a better adverse effect profile than morphine, but larger studies of longer duration are needed to gather more comparative data. Source: Reid CM, Martin RM, Sterne JAC, et al. Oxycodone for cancer-related pain. Meta-analysis of randomized controlled trials. Arch Intern Med. 2006(Apr);166(8):837-843. < Back to Top > Update: Recent Botulinum Toxin A Pain ResearchBotulinum toxin A is a fermented culture of Clostridium botulinum, the gram-positive anaerobic bacterium that causes botulism. The crude toxin is a protein, which is purified and vacuum-dried, and then small amounts are combined with saline or another liquid for therapeutic injection into muscle or other tissues (Kedlaya 2006). Research studies that show botulinum toxin A as an effective therapeutic modality for chronic pain appear to be increasing, as evidenced by the following 4 reports released in May 2006.
Sources: Bergfeldt U, Borg K, Kullander K, et al. Focal spasticity therapy with botulinum toxin: effects on function, activities of daily living and pain in 100 adult patients. J Rehabil Med. 2006(May);38(3):166-171. Gobel H, Heinze A, Reichel G, et al. Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport®) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study. Pain. 2006(May); [epub ahead of print]. Jabbari B, Ney J, Sichani A, et al. Treatment of refractory, chronic low back pain with botulinum neurotoxin a: an open-label, pilot study. Pain Med. 2006(May-Jun);7(3):260-264. Kedlaya D. Botulinum toxin: overview. Emedicine from WebMD. 2006. Available at http://www.emedicine.com/pmr/topic216.htm. Accessed checked 6/20/06. Ney JP, Difazio M, Sichani A, et al. Treatment of chronic low back pain with successive injections of botulinum toxin a over 6 months: a prospective trial of 60 patients. Clin J Pain. 2006(May);22(4):363-369.< Back to Top > Pregabalin Improves Sleep in Patients with PainAn analysis of 13 randomized controlled trials evaluated the effect of pregabalin on sleep in patients with the chronic pain from diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia syndrome, osteoarthritis, or spinal cord injury. Pregabalin (Lyrica®) is an anticonvulsant that has been approved in the US for the treatment of diabetic peripheral neuropathy and postherpetic neuralgia. In this analysis, sleep disturbance was evaluated secondarily to pain relief; efficacy was measured using the Medical Outcomes Study Sleep (MOS-Sleep) scale during trials of 5 to 13 weeks, plus patients’ sleep diaries. Pregabalin demonstrated significant reductions in pain and “sleep disturbance,” as well as significant improvements in the “overall sleep index” and “sleep-adequacy” sections of the MOS-Sleep scale. Benefits were reported at week 1 and continued through the 13 week study period by all pain groups except the osteoarthritis group, which showed significant improvement in sleep measures in spite of the fact that it did not reduce pain. One trial of healthy volunteers evaluated pregabalin against placebo; polysomnography results showed that the treatment group experienced decreased nighttime awakenings and a significantly longer time in stages III-IV sleep.Clinical Conclusions: This meeting abstract did not provide complete data on the results of the 14 total trials, but the investigators conclude that using pregabalin for selected patients may provide pain relief and better sleep quality with a lower risk of drug abuse. In addition, they state that “the beneficial effect of pregabalin on sleep appears to be at least partly independent of pain relief.” [However, because pregabalin induces drowsiness and potentially vision disturbances, patients should monitor their reactions to the drug before driving or participating in any activity that might result in accidental injury. – SB. Leavitt, PhD.] Source: Freeman R, van Seventer R, Murphy TK, et al. Pregabalin rapidly and significantly improves sleep disturbances in chronic pain syndromes and is associated with sleep improvements in healthy volunteers. 58th Annual Meeting of the American Academy of Neurology. 2006. Abstract EV1.014. < Back to Top > Corticosteroids Effectively Reduce Postoperative PainIneffective relief of moderate-to-severe postoperative pain can delay recovery, reduce patient satisfaction, and increase healthcare costs. In an extensive literature review in the June issue of Journal of Bone and Joint Surgery, the authors discuss 4 studies supporting the fact that moderate to severe postoperative pain is experienced by 30% to 77% of patients and is, oftentimes, poorly managed. The investigators further reviewed evidence-based literature to determine whether corticosteroids are safe and effective for pain relief in the early postoperative period. Clinical studies evaluated the use of glucocorticoids following orthopedic surgery, foot and ankle surgery, abdominal surgery, trauma, and spinal cord injuries. Effectiveness plus the frequency and severity of side effects were examined for steroids administered by different methods and medical specialties. The pathophysiology of postoperative pain and the mechanism of action of corticosteroids were analyzed in detail. Because surgery creates tissue damage and resultant pain and inflammation, the powerful anti-inflammatory characteristics of corticosteroids can be used to reduce pain following surgery. Evidence shows that adverse effects with corticosteroid use is proportional to the duration and strength of treatment. The investigators concluded that the research shows good levels of evidence favoring corticosteroids, alone or with local anesthetic agents, for short-term use in safely reducing pain after surgery.Investigator Comments: While the conclusion supports the use of corticosteroids for acute postoperative analgesia in patients who are otherwise healthy, the investigators caution practitioners that a standard protocol for dosage and mode of administration has not been determined. They further comment that these agents can adversely affect many organ systems and, thus, there is potential for numerous side effects, especially during chronic use. Finally, they stress the need for large controlled studies to validate the use of corticosteroids, specifically the long-acting dexamethasone in conjunction with anesthetics similar to bupivacaine. Source: Salerno A, Hermann R. Efficacy and safety of steroid use for postoperative pain relief. J Bone Joint Surg. 2006(Jun);88-A(6):1361-1372. < Back to Top > Validity of Iatrogenic Opioid Addiction QuestionedInvestigators conducted a systematic review of the literature for evidence relating to iatrogenic addiction in patients treated for acute and subacute (moderate duration) pain with opioid medications. The search yielded 1,943 articles, of which 53 qualified for review in detail, and 41 met basic criteria for inclusion in the review. There were no randomized trials or comparative longitudinal studies identified in the literature, and 9 studies of low methodological quality suggested conflicting findings. Practice Pointer: Overall, the authors note that studies of better methodological quality will be necessary to provide more valid evidence for or against iatrogenic addiction. They concede that their systematic review, although very extensive, could not adequately resolve the question of whether or not the risk for such addiction in patients treated with opioids for acute or subacute pain is of clinical significance. [Patients and practitioners alike are sometimes concerned that prescribed opioid use of even short- or moderate-term duration might induce addiction as a result of the medical intervention (i.e., iatrogenic). It is not surprising that this apprehension is unsupported by clinical evidence; according to accepted definitions, “true addiction” in patients without prior substance abuse or dependence takes much longer to emerge and involves a cluster of behavioral symptoms developing over time. – SB. Leavitt, PhD.] Reference: Wasan AD, Correll DJ, Kissin I, O’Shea S, Jamison RN. Iatrogenic addiction in patients treated for acute or subacute pain: A systematic review. J Opioid Management. 2006;2(1):16-22. See also: How is opioid addiction different from dependence or tolerance? Pain Treatment Topics, FAQs. Available at: http://www.pain-topics.org/faqs/index1.php#tolerance. Access checked 6/22/06. < Back to Top >
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Across the age groups, about 44% of child and infant records had pain scores. Scores for infants under 1 year and toddlers aged 2 to 4 were recorded for about 23% of each group, while older children between 5 and 18 years of age had the highest percentage of pain documentation at about 53%.
Patients with primary headaches, like migraine, frequently have tenderness in the sub-occipital region of the head. This study included 101 patients who experienced treatment-refractory headache on 15 or more days per month. Patients were diagnosed with migraine, cluster headache, new daily persistent headache, or hemicrania continua (a rare type of headache with continuous pain on one side of the face).