Pain
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Randomized Controlled Trial Comparative Study Clinical Trial
Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR).
Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients' usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen. ⋯ GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study. Somnolence, nausea, constipation, and dizziness were the most common drug-associated side effects. In conclusion, OTFC was more effective than MSIR in treating breakthrough cancer pain.
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Randomized Controlled Trial Clinical Trial
Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain.
Both mu opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are implicated in the regulation of neuropathic pain in post-nerve injury preclinical pain models. This study characterizes the effects of intravenously infused alfentanil (a mu-receptor agonist) and ketamine (an NMDA-receptor antagonist) on human neuropathic pain states, characterized by allodynia and hyperalgesia. Using diphenhydramine as the placebo, alfentanil and ketamine infusions were given in a randomized double-blind fashion 1 week apart via a computer-controlled infusion (CCI) pump that was programmed to target plasma levels of alfentanil at 25, 50 and 75 ng/ml and ketamine at 50, 100 and 150 ng/ml. ⋯ Therefore, clinical utilization of opioids with careful titration may be beneficial in post-nerve injury patients with partial deafferentation. With the absence of significant CNS side effects, the ketamine infusion not only demonstrated the well-documented spinal cord mechanism of the NMDA receptor, but the result of the current study also suggests that a peripheral mechanism of NMDA receptor may exist. The relationship between central sensitization and regulation of peripheral NMDA-receptor expression requires further investigation.
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Meta Analysis
Seeking a simple measure of analgesia for mega-trials: is a single global assessment good enough?
We sought to investigate the potential of using a simple global estimation ('How effective do you think the treatment was?') as a measure of efficacy by comparing it with at least 50%maxTOTPAR (at least 50% of the maximum possible pain relief) in acute pain studies. One hundred and fifty randomized, double-blind trials included in 11 systematic reviews of single dose, oral analgesics for postoperative pain were used as a source of data. The relationship between the proportion of patients reporting the top two or three values on a five-point global scale and the proportion with at least 50%maxTOTPAR was investigated. ⋯ Individual patient data were also used from four randomized, placebo-controlled, double-blind trials in postoperative pain. The frequency distribution for %maxTOTPAR was plotted for patients reporting each of the five categories on the global scale. A global assessment provides similar measures of analgesic efficacy as TOTPAR derived from hourly measurements, but the effects of adverse effects have yet to be understood.
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Randomized Controlled Trial Clinical Trial
Habituation of the early pain-specific respiratory response in sustained pain.
Neurokinin-1 receptor and mu-opioid receptor agonists affect respiratory rhythm when injected directly into the preBötzinger brainstem complex, which is the hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999) 1566). Early stress-induced analgesia (SIA) is naloxone-insensitive and as such considered independent of the activation of the mu-opioid system. Prolonged application of electrical shocks, however, produces analgesia that is mediated by the mu-opioid system (Science 208 (1980) 623). ⋯ In the early stage of pain, all monitored variables (respiration rate, minute ventilation volume, and inspiratory and expiratory flow rates) were elevated to statistically significant degrees when compared to measurements taken at baseline or during control infusion. Only respiration rate continued to be significantly elevated in sustained pain. We concluded that rhythmogenic neurons in the preBötzinger brainstem complex appear as the likely target for pro-nociceptive and anti-nociceptive input, explaining both the observed initial facilitation and subsequent habituation of respiration in early and sustained pain.
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Although individuals with fibromyalgia syndrome (FMS) consistently report wide-spread pain, clear evidence of structural abnormalities or other sources of chronic stimulation of pain afferents in the involved body areas is lacking. Without convincing evidence for peripheral tissue abnormalities in FMS patients, it seems likely that a central pathophysiological process is at least partly responsible for FMS, as is the case for many chronic pain conditions. Therefore, the present study sought to obtain psychophysical evidence for the possibility that input to central nociceptive pathways is abnormally processed in individuals with long standing FMS. ⋯ Within series of stimuli, FMS subjects reported increases in sensory magnitude to painful levels for interstimulus intervals of 2-5 s, but pain was evoked infrequently at intervals greater than 2 s for control subjects. Following the last stimulus in a series, after-sensations were greater in magnitude, lasted longer and were more frequently painful in FMS subjects. These results have multiple implications for the general characterization of pain in FMS and for an understanding of the underlying pathophysiological basis.