Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of a 39-year-old man with severe pain due to unresectable squamous-cell carcinoma of the maxillary sinus that had invaded cranial bone and had metastasized to the cervical spine. Tolerance to opioids had developed, and high doses of transdermal, continuous intravenous, and epidural opioids did not control his pain. An acute episode of extremely severe head pain was immediately controlled with a subanesthetic dose of ketamine after failure of a stress dose of corticosteroid and intravenous lidocaine. Because the patient was terminally ill and invasive procedures were not options, we controlled his pain using a low-dose ketamine infusion until his death 13 days later. Ketamine may be a good co-analgesic for breakthrough pain and for severe pain caused by terminal cancer when invasive techniques are inappropriate. Its mechanism of action may include reversal of opioid tolerance in addition to an inherent analgesic effect.
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PMID:Effective treatment of severe cancer pain of the head using low-dose ketamine in an opioid-tolerant patient. 754 37

Chronic post-thoracotomy pain (CPP) is associated with surgical intercostal nerve injury. Like other forms of neuropathic pain, there is no ideal treatment. Nitroglycerin (NTG) has been found efficacious in acute pain, but has not been tested for chronic pain with neuropathic characteristics. The present study investigated the efficacy of NTG combined with the nonsteroidal anti-inflammatory drug etodolac for the treatment of CPP. Thirty of 129 patients who underwent thoracotomy within an 18-month period had moderate to severe pain that did not respond to etodolac. NTG, 5 mg/day, was added to the treatment. A significant reduction in VAS was observed on day 14 of treatment (from 66.7 +/- 11 to 42.1 +/- 5, P< 0.05). Similar changes were noted in breakthrough pain intensity and and sleep efficiency. The only side effect was mild headache, which was self-limited to the first few days of NTG administration. We conclude that NTG added to etodolac appears to be effective for the treatment of CPP, with minimal side effects. Further randomized blinded studies are required.
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PMID:Efficacy of transdermal nitroglycerin combined with etodolac for the treatment of chronic post-thoracotomy pain: an open-label prospective clinical trial. 1503 39

BACKGROUND: Fentanyl buccal tablet (FBT; FENTORA(R), Cephalon, Inc., Frazer, PA, USA) is indicated in the US for breakthrough pain in patients with cancer who are already receiving and are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain. For each individual patient, FBT should be titrated to the effective dose. OBJECTIVE: The primary objective was to characterize the pharmacokinetic parameters of FBT 400 microg administered as a single 400 microg tablet (regimen A) or as two 200 microg tablets given simultaneously (regimen B) and determine whether these are bioequivalent in healthy Japanese volunteers. Regimen C (two 200 microg tablets 30 minutes apart) was also compared as a secondary objective. METHODS: Healthy Japanese adults received regimens A, B, and C in a crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Serum fentanyl concentrations were determined in venous blood collected through 36 hours post dose. Regimens were declared bioequivalent with respect to bioavailability (as reflected by AUC(0-infinity), AUC(0-last), and C(max)) if the 90% confidence interval (CI) of the regimens' ratio fell within 0.80-1.25 (80%-125%). RESULTS: Twenty-nine volunteers (13 men, 16 women) were enrolled; 24 completed the study. Regimens A and B had bioequivalent systemic exposure parameters (B/A [90% CI]: AUC(0-infinity)108.4 [103.4, 113.7], AUC(0-last) 106.1 [100.7, 111.7], and C(max) 92.3 [83.2, 102.4]). Regimen C was bioequivalent to both A and B for AUCs, but only to B for C(max). Median time to C(max) was 45 minutes for regimen A and 60 minutes for regimens B and C. The most frequent AEs were dizziness, application-site erythema, headache, somnolence, nausea, and vomiting. All AEs were mild or moderate. CONCLUSIONS: Bioavailability of fentanyl after FBT 400 microg administered as a single tablet was bioequivalent to that after 2 simultaneously administered 200 microg tablets in healthy Japanese volunteers. AEs were mild or moderate.
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PMID:Relative Bioavailability of Fentanyl Following Various Dosing Regimens of Fentanyl Buccal Tablet in Healthy Japanese Volunteers. 1991 9

Fentanyl buccal tablet (FBT) is indicated for the treatment of breakthrough pain in patients who are already receiving, and who are tolerant to, opioid therapy for underlying, persistent cancer pain. Breakthrough pain may be severe or excruciating, and some patients may require high doses of rapid-onset opioids to obtain adequate analgesia. The objective of this study was to assess the dose proportionality of FBT over a range of 600-1300 microg in healthy subjects. This was a randomized, open-label, four-period, crossover, single-centre study of FBT (Fentora) conducted in healthy adult subjects who were not tolerant to opioids. The study included 120 men and women aged 18-45 years with a body mass index of 20-30 kg/m2 who had no clinically significant findings on medical and psychiatric histories, physical examination, ECG or standard clinical laboratory tests, and who had a negative urine screen for drugs and alcohol. Eligible subjects were randomized to one of four dose sequences: ABDC, BCAD, CDBA and DACB, where A, B, C and D were FBT doses from lowest to highest (600, 1000, 1200 and 1300 microg). Each dose of FBT was separated by a minimum of 7 days. Naltrexone 50 mg was administered to block the opioid receptor-mediated effects of fentanyl. Plasma fentanyl concentration was measured through 72 hours after placement of FBT. The main outcome measures, maximum plasma fentanyl concentration (C(max)) and area under the plasma drug concentration versus time curve from time zero to infinity (AUC(infinity)), were analysed to determine dose proportionality. Other pharmacokinetic parameters were also evaluated. Dose proportionality was concluded if the two-sided 90% confidence intervals (CIs) for the slopes of the C(max) versus dose and AUC(infinity) versus dose curves were completely contained within the range of 0.711-1.289. The safety and tolerability of FBT were assessed throughout the study. The slope for C(max) versus dose was 0.8627 (90% CI 0.7730, 0.9525), and the slope for AUC(infinity) versus dose was 0.9330 (90% CI 0.8738, 0.9922). Given that the CIs for C(max) and AUC(infinity) were within the predefined range of 0.711-1.289, dose proportionality was concluded over the 600-1300 microg range. The mean dose-normalized plasma fentanyl concentration reached 80% of C(max) within 25 minutes; plasma fentanyl concentration was maintained at this level for 3 hours after dose. No unexpected safety or tolerability concerns were noted in the naltrexone-blocked healthy subjects. Seventy-four subjects (68%) experienced adverse events (AEs); all were mild (56 [51%]) or moderate (18 [17%]). The most common AEs were nausea, dizziness and headache. No serious AEs were reported. The dose proportionality of FBT from 600-1300 microg was shown in healthy subjects. Based on the data, when FBT is titrated up to 1300 microg, a predictable and linear increase in systemic exposure can be expected. Currently, FBT is approved up to 800 microg. This study provides pharmacokinetic data to support a potential, expanded therapeutic dose range of FBT.
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PMID:Dose proportionality of fentanyl buccal tablet in doses ranging from 600 to 1300 microg in healthy adult subjects: a randomized, open-label, four-period, crossover, single-centre study. 2044 Dec 45

Perspectives of patients with fibromyalgia influence their likelihood of participating in randomized placebo-controlled trials and potentially clash with current, well-established methodology of randomized controlled trial design. Mandates to use only acetaminophen for breakthrough pain and that require discontinuation of concomitant medications, especially in studies lacking an active comparator arm, could bias a trial cohort to thereby reduce the generalizability of study findings and conclusions. This study evaluates factors affecting willingness to participate in such clinical trials, including the impact of altruism, payment, study duration, forced discontinuation of specific medications, and subject demographics for patients seen by rheumatologists proficient and avidly interested in treating fibromyalgia.
Curr Pain Headache Rep 2010 Dec
PMID:Patient-derived determinants for participation in placebo-controlled clinical trials for fibromyalgia. 2095 41

During the course of a psychophysical study of fibromyalgia syndrome (FMS), one of the subjects with a long history of headache and facial pain displayed an extraordinarily severe thermal allodynia. Her stimulus-response function for ratings of cutaneous heat pain revealed a sensitivity clearly beyond that of normal controls and most FMS subjects. Specially designed psychophysical methods showed that heat sensitivity sometimes increased dramatically within a series of stimuli. Prior exposure to moderate heat pain served as a trigger for allodynic ratings of series of normally neutral thermal stimulation. These observations document a case of breakthrough pain sensitivity with implications for mechanisms of FMS pain.
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PMID:Extreme thermal sensitivity and pain-induced sensitization in a fibromyalgia patient. 2211 Sep 17

Whereas most pain due to cancer can be relieved with relatively simple methods using oral analgesics, as suggested by WHO guidelines, some patients may have difficult pain situations that require more complex approaches. It is estimated that 10-20 % of cancer patients suffer from pain that is not easily relieved. There are a number of factors that may reduce the efficacy of opioids in the management of cancer pain. Neuropathic pain (NP) and breakthrough pain (BP), especially of the incident subtype, have been identified as challenges for clinicians. In several prognostic studies, these two mechanisms were associated with limited positive outcomes compared with other syndromes. Opioid-induced hyperalgesia has recently been described as representing a challenge for physicians in the clinical setting. The global response to opioids, including the development of adverse effects, typically varies by individual and is likely genetically determined. Moreover, clinical evidence suggests that different opioids may produce different effect profiles, and so it is more appropriate to consider the response to each individual opioid rather than general opioid response. This paper will review both pharmacological and procedural mechanisms and treatments of these difficult pain syndromes.
Curr Pain Headache Rep 2014 Feb
PMID:Managing difficult pain conditions in the cancer patient. 2440 50

Breakthrough pain is a distinct pain state that is common in patients with cancer pain and which is associated with significant morbidity in this group of patients. The aim of this article is to highlight important journal articles relating to breakthrough pain that have been published within the last year, including a systematic review of the epidemiology of breakthrough pain, the largest-ever study of the clinical features of breakthrough pain, and a network meta-analysis of the treatment of breakthrough pain.
Curr Pain Headache Rep 2014 Jun
PMID:Breakthrough cancer pain. 2476 Apr 89