The journal of pain : official journal of the American Pain Society
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Neonatal peripheral inflammatory insult might result in the alteration of neuronal development in the nociceptive circuit. During early postnatal period, neurotrophins play important roles in neural development and sensory nerve innervation in the central and peripheral nervous systems. In this study, we investigated mRNA expression for neurotrophic factors and their receptors in the dorsal root ganglia of rat pups during postnatal life after peripheral inflammation induced by injection of complete Freund's adjuvant (CFA) into hind paw on postnatal day 1. Our results showed that mRNA expression levels of alpha-calcitonin gene-related peptides, tropomyosin-related kinase-A (trkA), p75 neurotrophin receptor (p75(NTR)), and brain-derived neurotrophic factor (BDNF) elevated significantly after CFA treatment. Such an increase began 1 day after CFA treatment and lasted 2 to 3 days for trkA, p75(NTR), and BDNF. In contrast, there was no change in mRNA expression levels for neurotrophin-4/5, beta-nerve growth factor (beta-NGF), trkB, glial cell line-derived neurotrophin factor, and receptor protein tyrosine kinase protein. Our study demonstrated that neonatal peripheral inflammatory insult might result in molecular changes of neurotrophic factors, particularly in NGF receptors and BDNF, in the process of neuronal development and plasticity in primary afferents during early neonatal period. ⋯ Neonatal peripheral inflammation model has been used for the exploration of neuropathic pain mechanism for years. This work provided further detailed information about possible neurotransmitters and peptides involved in this process. This might also lead to future clinical application.
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It is not known if a cytokine cascade develops during muscle inflammation and whether cytokines contribute to muscle inflammatory pain. We measured plasma and tissue cytokine concentrations, and behavioral responses to noxious mechanical stimuli, after inducing inflammation in the gastrocnemius muscle and the hind paw of rats. Tissue and plasma samples were taken 3, 6, or 24 h after carrageenan or saline injection into one of the 2 sites. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and cytokine-induced neutrophil chemoattractant 1 (CINC-1) concentrations were measured. Hyperalgesia was present 3 h after carrageenan injection into the hind paw and muscle. The TNF-alpha was elevated significantly in the inflamed hind paw tissue (P < .001) but not in inflamed muscle tissue. IL-1beta was elevated 6 h after carrageenan injection in the hind paw tissue but only 24 h in the muscle tissue (P < .001). The IL-6 was elevated 3 h after injection in the hind paw tissue but only after 6 h in the muscle tissue (P < .01). The CINC-1 in plasma, muscle, and hind paw was elevated from 3 h to 24 h after carrageenan injection (P < .01). The release of IL-1beta and IL-6, known to mediate hyperalgesia elsewhere, is delayed in muscle inflammation compared with cutaneous inflammation, whereas TNF-alpha is not elevated during muscle inflammation. ⋯ The quality and mechanisms of muscle pain are different from that of cutaneous pain. So too is the pattern of cytokine release during inflammation. Inhibiting TNF-alpha is unlikely to be effective in managing inflammatory muscle pain, but other cytokines, notably IL-1beta and CINC-1, may prove useful therapeutic targets.
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Randomized Controlled Trial Comparative Study
Placebo-controlled comparison of a morphine/dextromethorphan combination with morphine on experimental pain and hyperalgesia in healthy volunteers.
In this double-blind, placebo-controlled, crossover study we compared the analgesic effect of a single oral dose of 30-mg dextromethorphan and 30-mg morphine combination (MS/DM) to 30 mg morphine (MS) alone and either placebo or 30 mg dextromethorphan (DM) on cutaneous sensitization induced by heat/capsaicin (topical) sensitization on the forearm and the brief thermal sensitization model on the thigh in 22 healthy volunteers. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation in both sensitization models and the painfulness of acute thermal noxious stimulation on the upper arm. Compared with placebo, both MS/DM and morphine had some effect on the secondary hyperalgesia and reduced the painfulness of a noxious thermal stimulus. The analgesic effect of MS/DM was not superior to that of morphine on any outcome measure. These results differ from preclinical studies with animal experimental pain models in which DM markedly potentiated the analgesic effects of opioids, but they are in accordance with recent clinical trials for chronic pain. ⋯ Adding dextromethorphan to morphine (1:1 ratio) did not enhance analgesia on measures of experimental cutaneous sensitization and acute noxious thermal stimulation in healthy volunteers. The results differ from preclinical studies but agree with clinical trials. Human experimental models of pain and neuronal sensitization, which are responsive to oral opioids, allow efficient study of opioid combination analgesics and simplify the process for determining the optimal dose and/or dose ratio.
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The purpose of this study was to document analgesic use for limb and clavicle injuries in the pediatric emergency department (ED) and to determine whether a physician-oriented pain scale form on the patient's chart would enhance the administration of analgesia. Patients 3 to 18 years old were recruited prospectively in our tertiary pediatric ED in Toronto. The study included 4 crossover periods, 2 with the pain scale form on the patient's chart and 2 without. A total of 310 patients were recruited, mean age was 10 years, 64% were boys, and 62% had sustained fractures. The mean pain score was 4.4. Only 90 (29%) patients received an analgesic in the ED, and 65 (72%) of them were ordered by a physician. Only 24 (20%) in the study group and 22 (14%) in the control group received sufficient analgesia (P = .13). The median time to physician-initiated analgesia after arrival was 2.0 hours (1.0 to 3.3 hours), without a significant difference between groups. Pain control was 4-fold more appropriate in children receiving opioids versus nonopioids. Physician pain reminders did not enhance, and other measures should be taken to increase the dispensing of analgesia. ⋯ This is the first study to evaluate whether the addition of a physician-oriented pain-scale form on the chart of patients with injuries improves administration of analgesia in the ED. We found that physicians do not give sufficient analgesia even with this reminder form.