The journal of pain : official journal of the American Pain Society
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The recently introduced fentanyl transdermal therapeutic system (TTS) with a drug release rate of 12.5 microg/h matches the lower dosing requirements of cancer pain control in children. It is likely that fentanyl TTS will be used in pediatrics with increasing frequency. We compiled the published evidence on pediatric applications of this drug formulation to help physicians get the most benefit from its use. Within this systematic review, a total of 11 observational clinical or pharmacokinetic studies were identified. There are no pediatric randomized or controlled cohort studies. Pharmacokinetic studies poorly described time-concentration profiles after application. The time to reach steady-state serum drug concentrations seems to be longer, clearance (expressed as liters per kilogram per hour) higher, and elimination half-life shorter in children than in adults. There are no fundamental differences in effect or profile of adverse effects compared with adults. Fentanyl TTS may be associated with less constipation compared with morphine use. Frequently, pediatric patients need supplemental mechanical fixation of the fentanyl TTS by means of medical tape. Younger patients tend to have a higher fentanyl requirement when referenced to body weight. Both parents and medical professionals are satisfied with fentanyl TTS to a higher degree than with individual analgesic pretreatment regimens. Fentanyl TTS is a promising option for chronic pain control in children. An approximate conversion factor of 45 mg/day oral morphine to 12.5 microg/h fentanyl TTS is used for initial therapy dose estimation in children receiving long-term morphine therapy. This is conservatively low to avoid respiratory depression. Daily oral morphine equivalent dose should be at least 30 mg/d before fentanyl TTS therapy is started with 12.5 microg/h. Evidence for superiority of fentanyl TTS treatment above conventional opioid administration is both scarce and of low quality. ⋯ The article gives a comprehensive overview of all pediatric data concerning the fentanyl TTS. Children may take longer to reach steady-state fentanyl serum concentrations than adults, and younger children may require higher doses referenced to body weight than older children or adults. Consequently, there is a need to provide sufficient medication in the phase of therapy initiation to prevent breakthrough pain. The 72-hour dosing schedule recommended by the manufacturers may not be applicable to children because of poor patch adhesiveness. The authors suggest to ensure firm fixation of the fentanyl TTS with additional medical tape if necessary and to change the fentanyl TTS after 48 hours. Transdermal fentanyl in children may exhibit fewer side effects when compared with other opioids, especially constipation. Randomized studies are urgently needed to definitively answer this question.
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Randomized Controlled Trial Comparative Study Clinical Trial
Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: a prospective pilot study.
Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that might develop after breast surgery. Like many other forms of neuropathic pain, it is relatively resistant to treatment and negatively affects the quality of life. A double-blind, randomized, placebo-controlled pilot trial was conducted to study the analgesic efficacy of perioperative administration of the N-methyl-D-aspatrate (NMDA) receptor antagonist amantadine in preventing PMPS after mastectomy plus axillary lymph node dissection (ALND). In the study group, a regimen of 200 mg/day of amantadine was started 1 day before surgery and continued for 14 days, whereas the control group received a placebo. Patients were required to indicate the exact location of their pain and to record its level at 1, 3, and 6 months after surgery. Neurologic examination and Quantitative Thermal Testing (QTT) were performed 1 and 6 months after surgery. On both the neurologic examination and the QTT, all patients, regardless of the perioperative intervention (amantadine or placebo), presented evidence for nerve injury, manifested primarily by painful hypoesthesia (anesthesia dolorosa) in the axilla or inner arm. PMPS persisted for the entire duration of the study in 82% of the patients who were available for follow-up. The average intensity of the pain was moderate in both groups and tended not to decline over time. No differences between the 2 groups in any of the outcome parameters reached statistical significance. According to the results of the present pilot study, the NMDA antagonist amantadine does not prevent the development of PMPS in patients who undergo breast surgery with ALND. ⋯ Breast surgery that involves ALND seems to uniformly cause nerve injury, which cannot be prevented by the perioperative administration of 200 mg of amantadine. It is most commonly presented by painful hypoesthesia or anesthesia dolorosa in the axillary/inner arm area, which is moderate in intensity and likely to persist for at least 6 months.
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Comparative Study
Factors associated with depressed mood in chronic pain patients: the role of intrapersonal coping resources.
The purpose of this study was to examine processes through which chronic pain can result in depressed mood and to determine whether intrapersonal coping resources, namely high self-esteem and optimism, affect these processes. We hypothesized that pain severity contributes to depressed mood largely because pain interferes with involvement in important pursuits. We then examined whether intrapersonal resources are directly associated with pain severity, interference, and depressed mood and whether resources moderate associations between pain and interference or between interference and depressed mood. Structured interviews containing psychometrically robust measures were conducted with 141 outpatients of a university hospital-affiliated chronic pain center. As predicted, interference mediated much of the association between pain severity and depressed mood, and high resources were associated with less severe pain, less interference, and lower depressed mood. The association between pain severity and interference was stronger for people with high than people with low intrapersonal resources. The pattern of results that emerged from this study illustrates that intrapersonal coping resources may affect chronic pain patients through a variety of differentiated mechanisms. Pain severity appears to have greater adverse impact on the activity of people who possess highly positive self-views and outlook, but these resources are also associated with better emotional status. ⋯ Pain had greater adverse impact on the activity of people with highly positive self-views and outlook, but these coping resources were also associated with better emotional status. Chronic pain sufferers with few resources may require different interventions than those with more positive views of themselves and the world around them.
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Calcitonin gene-related peptide (CGRP) and/or substance P (SP) immunoreactivity as well as isolectin B(4) (IB(4)) binding are commonly used to define peptidergic and non-peptidergic nociceptor populations, respectively. Although this demarcation is well supported in the mouse, there is accumulating evidence to suggest it is not so in the rat. Hence, this investigation was undertaken to evaluate and quantify the colocalization of the neuropeptides CGRP and SP with IB(4) binding sites and the transient receptor potential vanilloid subfamily type 1 (TRPV1) channel and to compare this colocalization between trigeminal (TG) and dorsal root ganglia (DRG) in adult rats. These findings illustrate that there is a substantial overlap ( approximately 45% in the DRG and approximately 30% in the TG) between peptidergic neurons (ie, CGRP- and SP-expressing) and neurons that bind IB(4) in rat sensory ganglia. However, there were also significant differences in the colocalization of these markers between the DRG and TG. For instance, in the DRG, significantly more CGRP-immunoreactive neurons also expressed IB(4) binding sites (44.5%) compared with the TG (27.5%). In contrast, significantly fewer CGRP-immunoreactive neurons in the DRG colocalized TRPV1 immunoreactivity (49.2%) compared with the TG (70%). Moreover, we directly assessed the colocalization of CGRP and IB(4) in the TG of rats and mice using a CGRP antibody that recognizes this peptide in both species. Thus, whereas only an approximately 10% overlap was observed in TG neurons of mouse, significantly greater overlap (approximately 35%) was observed in those of rat. ⋯ These data indicate that in adult rat sensory ganglia, there is not a clear distinction between the peptidergic and non-peptidergic nociceptor subclasses as a function of IB(4) binding. Furthermore, there are significant differences between the TG and DRG in the degree to which commonly utilized nociceptive neuronal markers are co-expressed. Taken together, the present findings dictate prudence when extrapolating experimental conclusions about the neurochemical classification of neurons between sensory ganglia or between species, including humans.
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This study evaluated sensory and biomechanical assets in 2 heel pain conditions with similar symptoms, entrapment syndrome of the nerve to abductor digiti quinti and myofascial syndrome of abductor hallucis. Thirty-three patients with unilateral heel pain and 20 asymptomatic subjects underwent pressure pain threshold measurement in the painful area in site A (medial process of calcaneal tuberosity, trigger point site of abductor hallucis) and site B (1 cm posteriorly to site A, where the nerve to abductor digiti quinti becomes most superficial) and contralaterally; electroneurography of posterior tibial nerve; evaluation of ground-foot reaction on a dynamic platform. Eighteen patients had electric shock-type pain (entrapment syndrome, Group 1), 15 had cramp-like pain (myofascial syndrome, Group 2). Pain thresholds on the affected side versus contralaterally were significantly lower in site B in Group 1 and in site A in Group 2 (P < .001). Nerve conduction velocity was slightly reduced in Group 1 (P = .05). Ground-foot reaction was significantly altered on the affected side in all patients versus asymptomatic subjects; a significant difference between the 2 sides was found for peak of force (F1) in Group 1 and for all parameters except temporal phase of peak of force (TF3) (P = .05) for Group 2 (P < .0001). The different sensory and biomechanical patterns of the 2 examined syndromes help the differential diagnosis and consequent therapeutic approach. ⋯ This study shows different sensory and biomechanical patterns in 2 algogenic conditions of the heel with similar pain location. These distinct patterns reflect different pathophysiologic mechanisms in the 2 cases, which has a potential significant impact on treatment.