The authors found that high intrathecal morphine concentrations lead to aseptic intrathecal inflammatory masses. The lack of effect of clonidine and the possible suppressive effects of clonidine on the local reaction suggest the utility of such coadministration.
Pain is the cancer related event that is most disruptive to the cancer patient's quality of life. Although bone cancer pain is one of the most severe and common of the chronic pains that accompany breast, prostate and lung cancers, relatively little is known about the mechanisms that generate and maintain this pain. Recently, we developed a mouse model of bone cancer pain and 16 days following tumor implantation into the intramedullary space of the femur, significant bone destruction and bone cancer pain-related behaviors were observed. A critical question is how closely this model mirrors human bone cancer pain. In the present study we show that, as in humans, pain-related behaviors are diminished by systemic morphine administration in a dose dependent fashion that is naloxone-reversible. Humans suffering from bone cancer pain generally require significantly higher doses of morphine as compared to individuals with inflammatory pain and in the mouse model, the doses of morphine required to block bone cancer pain-related behaviors were ten times that required to block peak inflammatory pain behaviors of comparable magnitude induced by hindpaw injection of complete Freund's adjuvant (CFA) (1-3mg/kg). As these animals were treated acutely, there was not time for morphine tolerance to develop and the rightward shift in analgesic efficacy observed in bone cancer pain vs. inflammatory pain suggests a fundamental difference in the underlying mechanisms that generate bone cancer vs. inflammatory pain. These results indicate that this model may be useful in defining drug therapies that are targeted for complex bone cancer pain syndromes.
. An automated flinch detecting system for use in the formalin nociceptive bioassay. J Appl Physiol 90: [2386][2387][2388][2389][2390][2391][2392][2393][2394][2395][2396][2397][2398][2399][2400][2401][2402] 2001.-The biphasic display of pawflinch behavior in the rat after injection of formalin into the dorsum of the hind paw is used for the screening of antihyperalgesic agents. Described and characterized here is a less labor-intensive system for counting flinch activity by detecting movement of a small metal band placed on the formalin-injected paw. A signal is generated as the band breaks the electromagnetic field of a loop antenna located under the rat and processed through an algorithm that determines flinch activity using 1) amplitude, 2) zero-voltage crossing, and 3) signal duration. Flinches are summed and stored over a selected collection interval throughout the assay for later analysis. Studies have validated the measures with respect to 1) system stability over time; 2) system-to-"practiced observer" correlation on flinch detection, r 2 ϭ 0.94; 3) system variables including time of day, sex, age, and body weight; and 4) 50% effective dose values similar to those previously reported for intrathecal morphine and the NMDA antagonist MK-801. formalin test; spinal sensitization; pain models; flinching behavior THE ESCAPE RESPONSE OR AGITATION evoked by a transient, strong stimulus attests to there being a close relationship between stimulus intensity, peripheral afferent discharge, and magnitude of the pain state as defined by response latency and magnitude. There are situations, however, in which the magnitude of the response to pain may exceed what would normally be anticipated, given the magnitude of the physical stimulus and the afferent traffic generated by that stimulus (31,45,47). These situations are loosely considered as reflecting a state of hyperalgesia, possibly arising from sensitization of the peripheral terminal and/or a central facilitation.Several preclinical models have been developed that may reflect the significance played by such facilitation on behavior. The common characteristic found in these models is the injury that is induced and its causing of the sensory axon to produce a persistent discharge. A frequently used method of producing injury in the rat is the subcutaneous injection of a small volume of irritant such as formalin into its hind paw. Typically, after the formalin injection, the rat displays a biphasic (phase I and phase II) incidence of flinching (rapid paw shaking) and licking of the injected paw (18,42,43). The behavioral syndrome produced by the injection of formalin into the paw has been widely used to define the pharmacology of systems that regulate facilitated processing. The "formalin test" has evolved into a widely used tool in the screening of analgesic and anti-hyperalgesic drugs (45).An important limitation of this behavioral model is its labor-intensive nature regarding data collection and the time required to train observers in its reliable implementation. ...
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