Do changes in brain sodium channels cause central pain?
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Brain↗
Biomedical subjects
N A Hagen
Publications and source records attributed to N A Hagen.
Targeting the N-methyl-D-aspartate receptor for chronic pain management. Preclinical animal studies, recent clinical experience and future research directions.
A 1967-1999 MEDLINE search of published reports evaluating the role of the glutamate N-methyl-D-aspartate (NMDA) receptor in pain identified 378 animal studies and 132 human studies. There is convincing evidence in these studies that the NMDA receptor mediates prolonged nociceptive behaviors in animal models and various chronic pain symptoms in the clinical population. Administration of older compounds, such as ketamine, dextromethorphan, and amantadine, which are now known to act as NMDA receptor antagonists, have recently been shown to alleviate chronic pain. For years, the pharmaceutical industry has been attempting to produce novel compounds that modulate NMDA receptor activity; however, the adverse effects associated with this class of drugs have prevented their widespread clinical use. Collaborative studies between basic researchers, clinical scientists, and clinicians are needed to delineate characteristics of NMDA receptor antagonism that predict optimal analgesic activity and an acceptable toxicity profile in patients with chronic pain.
Animals↗
Analgesic effect of oral ketamine in chronic neuropathic pain of spinal origin: a case report.
Ketamine is an injectable anesthetic induction agent that has been reported to have analgesic activity in pain from a variety of mechanisms, but predominantly in neuralgic and dysesthetic neuropathic pain. In this case report we illustrate the effectiveness of ketamine in a patient with neuropathic pain resulting from cauda equina trauma. Among the issues addressed are the role of pretreatment with haloperidol to prevent ketamine-induced psychomimetic effects, the potential for fewer side effects and a need for lower doses when ketamine is administered orally, and the need for further study regarding appropriate monitoring parameters during the titration phase. Oral ketamine can be effective in treatment refractory chronic neuropathic pain of spinal origin.
Administration, Oral↗
Cardiac pacemakers and implantable defibrillators in terminal care.
The use of cardiac pacemakers and arrhythmia control devices is increasingly common. The presence of a previously placed pacemaker or implantable cardioverter-defibrillator (ICD) in a terminally ill patient may result in medical and ethical issues for the patient, family, and healthcare provider. Two cases are presented to illustrate the complex issues that may arise in the terminally ill with a pacemaker or an ICD. Based on these cases and a review of published data, it is likely that the disabling of a previously placed pacemaker will neither hasten nor prolong the natural history of the underlying illness in most instances. There are uncommon but potentially severe adverse effects of disabling the pacemaker; therefore, pacemakers should generally be left intact in terminally ill patients. It is more difficult to generalize as to whether deactivation of an ICD is appropriate; in this case death may be hastened and the decision concerning an ICD will depend on the specific clinical scenario. Patient and family education regarding palliative care treatment goals and the function of pacemakers and other implanted arrhythmia control devices can help to alleviate anxiety surrounding the impact of this technology at the end of life.
Aged↗
How long do prepared epidural solutions remain sterile?
The purpose of this study is to determine whether prepared epidural solutions remain sterile when refrigerated prior to use. The sterility of all epidural solutions prepared by an outpatient pharmacy of a tertiary level cancer facility was tested both at the time of preparation and after 14 days of refrigeration. Over a seven-month interval, we found no incidence of epidural solution colonization in 84 submitted samples prepared for four patients. All four patients had good relief of pain with ambulatory epidural infusion, and none developed clinical evidence of infection. We conclude that selected ambulatory patients with severe cancer pain, who are managed in the home environment with permanent epidural catheters, can use preservative-free epidural solutions that have been prepared with the sterile technique and stored in a standard domestic refrigerator for up to 14 days.
Analgesia, Epidural↗
Methadone: outpatient titration and monitoring strategies in cancer patients.
Methadone can be an effective drug for cancer pain but it can also be difficult to use safely. It has been recommended that rotation to methadone from other opioids be undertaken in a hospital setting. The purpose of the study was to characterize the safety, toxicities, and outcomes of outpatient rotation to methadone for severe cancer pain in a heavily pretreated cohort of cancer patients. Data were collected through a retrospective review of consecutive patients from a tertiary level cancer pain clinic. Twenty-nine patients were rotated to methadone, 13 (45%) due to opioid toxicity and 16 (55%) because of either cost or difficulty swallowing their prior opioid. Eleven of 29 patients (38%) failed methadone due to rapidly progressive cancer, dose-limiting side effects, or other reasons, but the other patients were successfully rotated to methadone. Pain usually improved following rotation to methadone, but drowsiness from methadone was common. On average, it took 32 days to successfully rotate to methadone in the outpatient setting. Cancer patients with advanced disease and severe pain can be safely and effectively rotated to methadone in the outpatient setting. It takes considerably longer to stabilize these patients than patients on lower doses of opioid or those titrated in the inpatient setting. A careful monitoring system is needed to screen for evidence of toxicity.
Analgesics, Opioid↗
Reproducing a cancer patient's pain on physical examination: bedside provocative maneuvers.
While various aspects of the physical examination in pain patients have been validated, the value of screening maneuvers that reproduce a cancer patient's pain on physical examination has been less well defined. The purpose of this prospective case series is to better characterize the role of bedside provocative maneuvers as part of the comprehensive evaluation of cancer pain patients. Fifty consecutive patients referred to an ambulatory cancer pain clinic were evaluated; they described a total of 89 discrete pains. All or much of the pain that brought each patient to medical attention was reproduced by a provocative maneuver in 47 (94%) patients; 79 of 89 (89%) pains were elicited at the bedside. Pains that were not reproducible with any provocative maneuver included paroxysmal spells of pain, neuropathic pain, and steady headache. On the basis of the history, physical examination, and both positive and negative provocative maneuvers, all pains were characterizable as somatic, visceral, neuropathic, or mixed, and a pathophysiological basis for the pain was inferred in 85 of 89 (95%) pains. On the basis of this preliminary report, we conclude that provocative bedside maneuvers are usually able to reproduce a cancer patient's pain. They help to better characterize the pain and identify the pain sensitive structure, and should be a routine part of the comprehensive assessment of cancer pain patients. Further research is needed to validate the diagnostic role of standardized pain-provoking maneuvers in a variety of clinical situations.
Humans↗
Analgesic effect of hyperbaric oxygen for pain caused by cancer treatment.
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Adult↗
Putting clinical practice guidelines into the hands of cancer patients.
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Breast Neoplasms↗
Long-term glioblastoma multiforme survivors: a population-based study.
BACKGROUND: Long-term glioblastoma multiforme survivors (LTGBMS) are uncommon. The frequency which these occur in an unselected population and factors which produce these unusually long survivors are unknown. OBJECTIVES: To determine in a population-based study 1) the frequency of LTGBMS in a population and 2) identify which patient, treatment or tumor characteristics would predict which glioblastoma (GBM) patient would become a LTGBMS. METHODS: The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in southern Alberta between 1/1/75-12/31/91. Patient charts were reviewed and histology re-examined by a blinded neuropathologist. LTGBMS were defined as GBM patients surviving > or = 3 years after diagnosis. Each LTGBMS was compared to three age-, gender-, and year of diagnosis-matched controls to compare patient, treatment, and tumor factors to GBM patients without long-term survival. RESULTS: There were 279 GBMs diagnosed in the study period. Five (1.8%) survived > or = three years (range, 3.2-15.8 years). Seven additional long-term survivors, who carried a diagnosis of GBM, were excluded after neuropathologic review; the most common revised diagnosis was malignant oligodendroglioma. LTGBMS (avg. age = 45 years) were significantly younger when compared to all GBM patients (avg. age = 59 years, p = 0.0001) diagnosed in the study period. LTGBMS had a higher KPS at diagnosis (p = 0.001) compared to controls. Tumors from LTGBMS tended to have fewer mitoses and a lower Ki-67 cellular proliferative index compared to controls. Radiation-induced dementia was common and disabling in LTGBMS. CONCLUSIONS: These data highlight the dismal prognosis for GBM patients who have both a short median survival and very small chance (1.8%) of long-term survival. The LTGBMS were younger, had a higher performance status, and their tumors tended to proliferate less rapidly than control GBM patients. When long-term survival does occur it is often accompanied by severe treatment-induced dementia.
Adult↗
Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain.
BACKGROUND: The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half-life, which necessitates administration every 4 hours. This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain. METHODS: In a double-blind crossover study, 44 patients with stable cancer pain were randomized to controlled-release oxycodone or controlled-release hydromorphone, each given every 12 hours for 7 days. Pain intensity, nausea, and sedation were assessed by patients four times daily, and breakthrough analgesia was recorded. RESULTS: Thirty-one patients completed the study (18 women, 13 men; mean age, 56 +/- 3 years) and received a final controlled-release oxycodone dose of 124 +/- 22 mg per day and a final controlled-release hydromorphone dose of 30 +/- 6 mg per day. There were no significant differences between treatments in overall Visual Analogue Scale (VAS) pain intensity (VAS 28 +/- 4 mm vs. 31 +/- 4 mm), categorical pain intensity (1.4 +/- 0.1 vs. 1.5 +/- 0.1), daily rescue analgesic consumption (1.4 +/- 0.3 vs. 1.6 +/- 0.3), sedation scores (24 +/- 4 mm vs. 18 +/- 3 mm), nausea scores (15 +/- 3 mm vs. 13 +/- 3 mm), or patient preference. Two patients experienced hallucinations on controlled-release hydromorphone, but none did while receiving controlled-release oxycodone. CONCLUSIONS: Controlled-release oxycodone demonstrated excellent pharmacodynamic characteristics, analgesic efficacy, and safety as compared with controlled-release hydromorphone and represents an important new therapeutic option for cancer pain management.
Analgesics, Opioid↗
Cancer pain emergencies: a protocol for management.
Cancer is often associated with chronic pain, which can be managed by established algorithms. Cancer is also occasionally associated with sustained episodes of excruciating pain (cancer pain emergencies) that require rapid application of powerful analgesic strategies in a manner that is distinct from chronic pain management techniques. To clarify the utility of rapid opioid dose escalation in this setting, we reviewed the management of ten cancer pain emergencies in nine patients. After initial assessment, all patients were managed according to a protocol whereby intravenous boluses of opioid are administered with rapid upward titration until an effective analgesic dose is found. Using this technique, all patients had relief of their excruciating pain after a mean of 89 min (range, 4-215 min). No patient demonstrated evidence of significant toxicity. We conclude that repeated intravenous boluses of an opioid, doubling the dose every 30 min until analgesia is achieved, is effective and safe management of cancer pain emergencies. Validation of this protocol is required.
Adult↗
Neuropathic pain in cancer patients: mechanisms, syndromes, and clinical controversies.
The identification of a neuropathic pain syndrome in a cancer patient requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. If a tumor is directly involved in the etiology of the pain, oncologic treatment is an initial consideration and may include surgery, radiation, or chemotherapy. There is no single accepted algorithm for the analgesic treatment of neuropathic pain and a systematic approach utilizing therapeutic trials of specific agents at gradually increasing doses is warranted. A trial of opioids, perhaps in combination with an NSAID, is warranted. If the pain is relatively unresponsive to an opioid, a trial with an adjuvant analgesic is reasonable. For example, a tricyclic antidepressant might be selected early for patients with continuous dysesthesia, and early treatment with an anticonvulsant might be used if the pain is predominantly lancinating or paroxysmal. Other adjuvant analgesics can be selected if there is insufficient response to these agents. A trial of sympathetic blockade, pharmacologic, anesthetic or surgical, should be considered in patients with evidence of causalgia or reflex sympathetic dystrophy. Physiatric modalities such as massage, heat, or cold; counterstimulation or transcutaneous electrical nerve stimulation (TENS), and orthopedic interventions, such as braces and splints may be useful. Epidural injections or neurostimulation of the spinal cord or brain can be considered in selected cases where appropriate expertise is available. Treatment of neuropathic pain remains a challenge for both clinicians and patients. The complexity of syndromes and underlying etiologic mechanisms warrants further clinical trials to determine the best treatment modalities for individual pain syndromes.
Diagnosis, Differential↗
Prospective study of postoperative magnetic resonance imaging in patients with malignant gliomas.
PURPOSE: We studied the natural history of postoperative enhancement on magnetic resonance (MR) scans in patients with malignant glioma to determine the following: (1) when a postoperative MR scan most accurately shows residual enhancing tumor; and (2) whether repeated doses of the contrast agent gadopentetate dimeglumine (Gd-DTPA) were well tolerated. PATIENTS AND METHODS: Seventeen patients with malignant glioma underwent tumor resection; four (24%) had nonenhancing tumors preoperatively. Serial MR scans were performed on postoperative days 1, 3, 5, 7, 14, and 21 and were analyzed qualitatively and quantitatively. The evolution of enhancement and subacute hemorrhage were described and measured. A uniform schedule of postoperative dexamethasone administration was used in all but four patients (24%) (each required higher doses to maintain neurologic function). RESULTS: Nontumoral, marginal (i.e., postsurgical) enhancement, potentially mimicking residual tumor, developed in eight patients (53%), including tumors that were nonenhancing preoperatively, and was maximal from days 5 to 14. Tumor enhancement was optimally visualized on postoperative days 3 to 5. Nine of 10 patients (90%) with gross residual enhancing tumor showed an increase of enhancing tumor size during the study. Methemoglobin was detected at some time in all patients (100%) and was usually minor, but in six (35%) it interfered with residual tumor assessment. The 97 doses of Gd-DTPA, administered in 17 patients, were well tolerated. CONCLUSION: When accurate assessment of residual enhancing tumor is needed in patients with malignant glioma, an MR scan performed on postoperative days 3 to 5 should minimize the confounding effects of postsurgical enhancement and methemoglobin. The repeated administration of Gd-DTPA over several weeks is well tolerated.
Adolescent↗
Regulated analgesics and pain control.
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Analgesics, Opioid↗
Cooperative hernia study. Pain in the postrepair patient.
BACKGROUND: The Cooperative Hernia Study assessed postoperative pain in a prospective trial as part of a larger study looking at the recurrence rate and other morbidity of the Bassini, McVay, and Shouldice repairs. METHODS: Patients were randomized to one of three surgical hernia repairs. Patients were seen in follow-up at 6, 12, and 24 months and were assessed for the presence of pain, numbness, paresthesia, and recurrence. RESULTS: Three hundred fifteen patients were seen in follow-up, with 276 seen at the 2-year mark. At 1 year, 62.9% of patients had groin or inguinal pain and 11.9% of patients had moderate to severe pain; 53.6% had pain and 10.6% of patients continued to report moderate to severe pain 2 years postoperatively. The predictors for long-term postoperative pain were as follows: absence of a visible bulge before the operation (p < 0.001); presence of numbness in the surgical area postoperatively (p < 0.05); and patient requirement of more than 4 weeks out of work postoperatively (p < 0.004). Three distinct chronic pains were identified. The most common and most severe pain was somatic, localized to the common ligamentous insertion to the public tubercle. The second was neuropathic and was referable to the ilioinguinal or genitofemoral nerve distribution. This was likely because of injury to the genitofemoral nerves, either at surgery or subsequently by encroachment of scar. The third pain was visceral, ejaculatory pain. Twenty-four percent of patients had postoperative numbness at 2 years, independent of the type of repair. Numbness was most common in the distribution of cutaneous branches of the ilioinguinal and iliohypogastric nerves. CONCLUSION: Pain or numbness are common late sequelae of traditional external surgical hernia repairs. Strategies need to be developed to reduce the risk of these complications.
Adult↗
Malignant supratentorial glioma in the elderly: is radiotherapy useful?
OBJECTIVES: To determine (1) if radiotherapy (RT) improves survival or neurologic function in elderly patients with malignant supratentorial glioma (MSG) and (2) which prognostic factors predict survival. BACKGROUND: The prevalence of MSG is increasing because both the number of elderly patients and the age-adjusted incidence are increasing. Because age is a powerful negative prognostic factor in MSG, it is not clear if RT is useful in the elderly. DESIGN/METHODS: We retrospectively studied 103 patients from the Southern Alberta Cancer Registry diagnosed January 1, 1978, to December 31, 1993, aged 70 yrs, with MSG in whom sufficient clinical and follow-up information was available. Multiple treatment and patient factors were compared with survival and neurologic function score. Diagnosis was confirmed in 15 (14.6%) by biopsy, in 66 (64.1%) by resection, and in 22 (21.4%) by clinical course and typical radiographic appearance only. RESULTS: All patients died and median survival was 3.9 months. Better neurologic function at diagnosis and administration of RT were independently associated with significantly longer survivals (p = 0.001 and < 0.001; log rank test). However, RT was only associated with longer survival in patients aged less than 80 years. Neurologic status only rarely improved following RT. CONCLUSIONS: The prognosis for elderly patients with MSG is poor. RT is unlikely to benefit patients who are aged 80 years or older. RT has a short-lived benefit for patients who are functionally disabled.
Aged↗
Sharp, shooting neuropathic pain in the rectum or genitals: pudendal neuralgia.
In 18 mo, the author encountered six patients with severe sharp, shooting genital or rectal pain. All patients had cancer, diabetes, or both, and all patients responded dramatically to adjuvant analgesics with or without opioid analgesics. The author concludes that the presence of pudendal neuralgia should prompt a search for an underlying cause, and that this severe neuropathic pain syndrome is effectively managed with adjuvant analgesics.
Aged↗