In response to concerns over the clinical relevance of analgesic testing paradigms which involve acute nociceptive stimuli, the present research examined the utility of the conditioned place preference (CPP) paradigm as a novel approach for determination of analgesic drug efficacy against chronic nociception. Rats display preferences for environments that have been previously paired with positively reinforcing drugs; whether place preference to the negatively reinforcing effects of analgesic drugs in an animal model of chronic pain occurs is yet unknown. The present research sought to determine whether animals experiencing chronic pain would display a place preference for an environment paired with analgesic drug treatment. Persistent inflammatory nociception was induced by unilateral injections of complete Freund's adjuvant (0.1 ml) into the rat hind paw. Place preference to the opiate agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the non-steroidal anti-inflammatory drug (NSAID) indomethacin was examined in 3 separate experiments. Rats received 8 counter-balanced conditioning trials (4 drug, 4 no-drug) of 60 min each with various drug doses (morphine: 3.0 and 10.0 mg/kg; indomethacin: 2.5 and 5.0 mg/kg; MK-801: 0.03, 0.1 and 0.3 mg/kg, i.p.) or vehicle serving as the reinforcing stimuli in a 3 compartment (2 stimuli, 1 neutral) place preference apparatus. In general, morphine place preference was observed in both inflamed and non-inflamed groups; inflamed groups exhibited enhanced morphine place preference than non-inflamed groups. MK-801 produced a low-dose place preference in inflamed animals; higher doses of MK-801 produced a place aversion in both inflamed and non-inflamed groups. Indomethacin failed to produced place preference in either inflamed or non-inflamed groups. These data demonstrate that the negatively reinforcing properties of analgesic drugs can be assessed via the CPP paradigm. In addition, this paradigm offers greater clinical relevance as animals determine drug efficacy without the involvement of high-intensity, phasic nociceptive stimulation.
The formalin test is a well-established model for assessing inflammatory nociceptive processes and analgesic drug effects. Previous research established the validity of an ordinal relationship among three well-defined pain behavior categories used to compute a composite pain score (CPS). However, optimal weights had not been validated. The present research used data from Coderre et al. (1993) and from Sufka and Roach (1996) to determine and validate optimal pain behavior category weights. Based on multiple regression analyses and Pearson correlations, optimal weights of 1 and 2 are proposed for behavior categories 2 and 3, respectively; behavior category 1 is not scored. These results are consistent with the work of Abbott et al. (1995) and Coderre et al. (1993) in that the ordinal relationship among category weights is preserved, and extend previous work by establishing optimal category weights.
Xanthohumol (XN) is the major prenylated flavonoid in hop plants and as such a constituent of beer. Pharmacological studies have shown that XN possesses marked antioxidant and antiproliferative effects. In order to study the resorption and metabolism of this compound, reversed-phase high-performance liquid chromatography is used for the determination of XN in rat plasma, urine, and feces. In session one, rats receive either oral or intravenous (iv) administration (20 mg/kg body weight) of XN. In session two, rats receive oral administration of 50, 100, 200, 400, and 500 mg/kg body weight XN for bioavailability studies at various dose levels. Plasma, urine, and feces are collected at varying time points and assayed for their XN content. Plasma levels of XN fell rapidly within 60 min after iv administration; no XN is detected in plasma after oral administration in either session. XN and its metabolites are excreted mainly in feces within 24 h of administration. The method is a reliable tool for performing studies of XN in different biological material.
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