Jimenez-Andrade JM, Ghilardi JR, Castaneda-Corral G, Kuskowski MA, Mantyh PW. Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain. Pain 152, 2564–2574 (2011).
Using a mouse model of prostate cancer-induced bone pain, the authors injected anti-NGF at 14 days (before tumor-induced nerve sprouting) and 35 days (after extensive nerve sprouting) after tumor injection. They observed pain-related behaviors as well as morphological changes in bone using immunohistochemistry, and laser confocal microscopy to observe nerve fibers, blood vessels and macrophage invasion. Preemptive administration was more effective than late administration of anti-NGF but both times of injection resulted in reduced nociceptive behaviors, sensory and sympathetic nerve sprouting and neuroma formation. As is true for most cancers, the prostate cancer used in this study grew in a pattern of individual cell colonies that had a limited half-life due to their proliferating, metastasizing and undergoing necrosis as the parent cell colony outgrows its vascular supply. Similar changes are seen in the sensory and sympathetic nerve fibers that innervate the tumor. Newly formed nerves are found in the daughter cell colonies. This study demonstrates that the pains associated with cancer are nociceptive, neuropathic and tumorigenic in origin. The innervation of a tumor seems to evolve with the neoplasm itself; this could explain why there is no direct correlation of pain with the extent of a neoplasm in bone. It also suggests that anti-NGF may be clinically useful, if the reported undesirable side effect of accelerated joint destruction can be abolished. This study is a model of translational research with both behavioral and histological end points.
– Written by John D Loeser
Mezei L, Murinson BB; Johns Hopkins Pain Curriculum Development Team. Pain education in North American medical schools. J. Pain 12, 1199–1208 (2011).
This article is a shot across the bow of medical education in the USA and Canada. It very nicely documents the mismatch between the magnitude of the problems of acute and chronic pain management and the curricular content in our schools of medicine. It is no wonder that the graduates of our medical schools do not like to see patients with pain and do not do a good job relieving their pain and suffering. We teach them very little of the knowledge base, skills or attitudes that are important in pain management. Mezei and her coauthors have undertaken a thorough survey of the Association of American Medical Colleges (AAMC) accredited schools, utilizing the curricular database maintained by the AAMC. Individual topics are identified and the time devoted to pain education has been quantified. Many medical schools do not have any curricular content devoted to pain; approximately half of the schools devote less than 5 h to all pain topics. Less than 4% of the schools have an integrated course devoted to pain; almost all of the pain content in the overwhelming majority of schools is found in courses that are focused upon other topics. Resources for creating pain courses abound; the International Association for the Study of Pain has published curricular materials for over 30 years and many other societies have generated curricular guidelines as well. The problem, of course, is the lack of concern for pain by those responsible for curricular content. They do not realize that the disability caused by pain in the working years in the USA is greater than the sum of disability due to cancer, heart disease, AIDS and stroke. The costs of pain to our society and to the individuals who suffer from it are immense. The time has come for those active in the pain world to forcefully lobby within their academic institutions to rectify this situation. Mezei, Murinson and the Johns Hopkins Hospital Group have provided us with the facts to lead our mission.
– Written by John D Loeser
Chapman CR, David J, Donaldson GW, Naylor J, Winchester D. Postoperative pain trajectories in chronic pain patients undergoing surgery: the effects of chronic opioid pharmacotherapy on acute pain. J. Pain 12, 1240–1246 (2011).
This fascinating, convenience sample, cohort study demonstrated that chronic pain patients resolve their acute postoperative pain slower than those who do not have chronic pain. Moreover, chronic pain patients who use opioids have a higher initial postoperative pain score than those who do not and resolve their acute pain at the same rate as those who did not use opioids preoperatively. Hence, a chronic pain patient who is using opioids who then undergoes a surgical procedure has more pain immediately after surgery and a higher pain level that persists throughout the recovery period. This is true for both pain at rest and movement-induced pain. This suggests, as others have written before, that patients who come to a surgical procedure with a history of opioid intake need particular attention to their pain relief in the postoperative period. It is also another reason why chronic opioid therapy needs careful consideration.
– Written by John D Loeser
Choi KC, Kim JS, Kang BU et al. Changes in back pain after percutaneous endoscopic lumbar discectomy and annuloplasty for lumbar disc herniation: a prospective study. Pain Med. 12, 1615–1621 (2011).
Percutaneous lumbar discectomy and annuloplasty were performed on 58 patients with leg and back pain of at least 6 weeks‘ duration, secondary to lumbar disc herniation as confirmed on MRI and/or CT scan. Exclusion criteria included patients with foraminal herniation, multilevel herniation, spinal stenosis, spondylolisthesis, scoliosis or prior lumbar surgery. Preoperative radiologic assessment was carried out on disc height, type of herniation, degree of spinal canal compromise and degree of disc degeneration. Pain intensity (Visual Analog Scale) and functional status (Oswestry Disability Index) were evaluated preoperatively and at 1, 6 and 24 months. A total of 52 patients with a mean age of 36.2 years were included in follow-up, 41 of which received treatment at the L4–5 level. Mean scores preoperatively and at 1, 6 and 24 months respectively were as follows: Visual Analog Scale for back pain = 6.6, 4.2, 2.8 and 2.5; Visual Analog Scale for leg pain = 7.6, 3.3, 1.7 and 1.8; Oswestry scores = 55.9, 34, 19.1 and 12.7. Eighteen patients (34.6%) did not achieve a favorable outcome from the procedure. It was noted that those patients with advanced disc degeneration achieved a significantly worse outcome than those with mild disc degeneration (odds ratio = 6.316). No other radiographically observed parameter correlated significantly with procedural outcome.
– Written by Michael Erdek
Burton AW, Mendoza T, Gebhardt R et al. Vertebral compression fracture treatment with vertebroplasty and kyphoplasty: experience in 407 patients with 1156 fractures in a tertiary cancer center. Pain Med. 12, 1750–1757 (2011).
A retrospective review was carried out of 407 patients who received either vertebroplasty (VP) or kyphoplasty (KP) treatment for a total of 1156 fractures over a 7.5-year period. Patients‘ pain was assessed with the Brief Pain Inventory and related symptoms by the Edmonton Symptom Assessment Scale. Average patient age was 62.9 years, while 43% of fractures were due to multiple myeloma and 35% to osteoporosis. Of the 536 procedures performed, 262 were VP, 156 were KP and 111 were combined procedures. An average of 2.8 fractures per patient were treated. Of the patients treated, 24% experienced subsequent fractures, 46% of which occurred at a level adjacent to previous treatment. Pain and symptom data at up to 60 days postintervention were only available for 170 of the 407 patients treated. Pain scores decreased by an average of 1.4 points (p < 0.001) while symptom scores decreased for fatigue, depression, anxiety, drowsiness (all p < 0.001) and difficulty thinking clearly (p < 0.006). A total of 134 complications were observed, the most common of which were paravertebral cement spread (38.8%), intradiscal extrusion (28.4%) and venous extrusion (23.9%). Complications occurred more frequently in combination procedures than in VP (p < 0.02) or KP (p < 0.003) alone. No significant complication difference was observed between VP and KP (p < 0.27). Symptomatic epidural extrusion occurred in four patients, two of whom required open surgical decompression with subsequent symptom resolution.
– Written by Michael Erdek
Jensen R, Tassorelli C, Rossi P et al.; Basic Diagnostic Headache Diary Study Group. A basic diagnostic headache diary (BDHD) is well accepted and useful in the diagnosis of headache. A multicentre European and Latin American study. Cephalalgia 31, 1549–1560 (2011).
The diagnosis of headaches is made based on diagnostic criteria defined in the International Classification of Headache Disorders. Due to recall bias, headache diaries provide important information. This study describes the validation of a basic diagnostic headache diary (BDHD) for migraine, tension-type headache and medication-overuse headache. The BDHD is translated into eight languages. The BDHD was adequate for the diagnosis of almost 96% of patients, with no differences between centers. The authors emphasize that the clinical interview and neurological examination is important in the diagnosis of headaches, but the BDHD may be a helpful tool in the diagnostic assessment of the most frequent of the primary headaches and may be useful before the patient‘s first consultation and integrated with the findings at interview.
– Written by Nanna B Finnerup
Niemi-Murola L, Unkuri J, Hamunen K. Parenteral opioids in emergency medicine – a systematic review of efficacy and safety. Scand. J. Pain 2, 187–194 (2011).
This is a systematic review of the efficacy and safety of parenteral opioids used in emergency medicine. All opioids, especially morphine, showed analgesic effect in emergency medicine patients and also in the prehospital setting. The most commonly used morphine dose was 0.1 mg/kg but evidence for the optimal opioid dose is scarce and more studies are needed in this area. Adverse effects were very variable. Only one out of 1266 patients was given naloxone for drowsiness and ventilator depression was very unlikely, suggesting that the use of opioids is relatively safe in emergency medicine. The authors also conclude that training of emergency personnel and prevention and treatment of opioid-induced nausea and vomiting is important.
– Written by Nanna B Finnerup
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.