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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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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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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Randomized Controlled Trial Comparative Study Clinical Trial
Caffeine attenuates delayed-onset muscle pain and force loss following eccentric exercise.
This double-blind, placebo-controlled, repeated-measures experiment examined the effects of a 5 mg . kg(-1) body weight dose of caffeine on delayed-onset muscle pain intensity and force loss in response to 64 eccentric actions of the dominant quadriceps induced by electrical stimulation. Low caffeine-consuming college-aged females (n = 9) ingested caffeine or placebo 24 and 48 hours following electrically stimulated eccentric exercise of the quadriceps. One hour after ingestion, maximal voluntary isometric contractions (MVIC) and submaximal voluntary eccentric actions were used to determine force loss during activation of damaged quadriceps and whether caffeine attenuates muscle pain intensity. Pain intensity was measured using a 0 to 100 visual analog scale. Caffeine produced a large (12.7 raw visual analog scale [VAS] units; -48%; Cohen's d effect size = -0.88), statistically significant hypoalgesia during the MVIC (t = -2.52; df = 8; P = .036). The reduction in pain scores during submaximal voluntary eccentric movements was smaller (7.8 raw VAS units; -26%, d = -0.34), as was the increase in MVIC force (4.4%; d = 0.13). ⋯ Eccentric exercise occurs when skeletal muscles produce force while being lengthened. For example, the biceps brachii muscles act eccentrically when a cup of coffee is lowered from the mouth to a tabletop. This experiment found that caffeine (equal to approximately 2 cups of brewed coffee) could produce a large reduction in pain resulting from eccentric exercise-induced, delayed-onset muscle injury. This finding may improve the quality of life of individuals who experience skeletal muscle pain after engaging in unaccustomed, eccentrically biased exercise.
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Comparative Study Clinical Trial
Pain catastrophizing, response to experimental heat stimuli, and post-cesarean section pain.
This prospective study assessed the relation between pain catastrophizing, response to experimental pain stimuli, and pain perceived by women after elective cesarean sections. Forty-seven women who were scheduled for elective cesarean section were enrolled in the study. Magnitude estimation to suprathreshold phasic and tonic heat pain stimuli was assessed 1 or 2 days before surgery. Women completed the Pain Catastrophizing Scale after the heat stimuli and again on the first postoperative day. During the first and second postoperative days, perception of pain intensity was assessed by visual analog scale at each analgesia request. A multiple regression analysis revealed that pain on the first postoperative day was predicted by patient response to preoperative tonic heat stimuli (r(2) = .167, P = .008). Pain on the second postoperative day was predicted by preoperative pain catastrophizing (r(2) = .139, P = .021). No significant association was observed between preoperative response to heat stimuli or pain catastrophizing and the patient's analgesic consumption in the obstetrical ward. It is concluded that pain catastrophizing and response to experimental tonic heat pain correlate with post-cesarean section pain. ⋯ This article presents psychological and psychophysical measures that may be of help in the prediction of post-cesarean section pain. It may therefore contribute to the treatment of the sequelae of the most common major surgical procedure performed in women in their reproductive years.