Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 & 40 mg), hydrocodone (15, 30 & 45 mg), hydromorphone (10, 17.5 & 25 mg) and placebo. Healthy adult volunteers (n=9) with sporadic prescription opioid abuse participated in 11 experimental sessions (6.5 hr in duration) conducted in a hospital setting. All three opioids produced a typical mu opioid agonist profile of subjective (increased ratings of liking, good effects, high and opiate symptoms), observer-rated, and physiological effects (miosis, modest respiratory depression, exophoria and decrements in visual threshold discrimination) that were generally dose-related. Valid relative potency assays revealed that oxycodone was roughly equipotent to or slightly more potent than hydrocodone. Hydromorphone was only modestly more potent (less than two-fold) than either hydrocodone or oxycodone, which is inconsistent with prior estimates arising from analgesic studies. These data suggest that the abuse liability profile and relative potency of these three commonly used opioids do not differ substantially from one another and suggest that analgesic potencies may not accurately reflect relative differences in abuse liability of prescription opioids.

Short-latency averaged responses in the C5 phrenic nerves to electrical stimulation (2.5-80 microA; 5-80 Hz; 150 microseconds pulse duration) of raphe pallidus (RP) and raphe obscurus (RO) were investigated in anesthetized, paralyzed, and artificially ventilated cats. The responses to stimulation of RO were excitatory, whereas a mixture of inhibitory and excitatory responses of lesser magnitude were observed after stimulating in RP. The maximal response was obtained from the ventral part of RO and consisted of early and delayed excitatory responses that were of equal magnitude in both left and right C5 phrenic nerve roots. The mean latency for the early response was 2.5 +/- 0.1 msec and for the delayed response was 7.0 +/- 0.2 msec. Both responses were elicited during inspiratory phase stimulation, but only the delayed response was present during expiratory phase stimulation. The stimulus threshold of the early response was 5 microA; the delayed response was elicited at currents as small as 2.5 microA. Early and delayed responses were affected in different ways by increasing stimulus current and by increasing stimulus frequency. Intravenous administration of serotonin receptor antagonists methysergide (0.1-0.7 mg/kg), metergoline (33-244 micrograms/kg), and cinanserin (1.5-9.0 micrograms/kg) caused significant dose-related reductions in the magnitude of the delayed response, but did not significantly affect the early response. These data suggest that the early and delayed excitatory responses are mediated by different neuronal pathways. The early response does not involve serotonin release, while the later response is mediated at least in part by activation of a serotonergic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

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The treatment of pain produced during the management of burn injury has been an ongoing problem for physicians caring for these patients. The main therapeutic option for analgesia has been the repeated and prolonged use of opioids. The adverse effects of opioids are well known but the long term use of opioids which produces tolerance with accompanying dose escalation and dependence is most problematic. Another potentially important consequence of opioid exposure that sometimes masks as tolerance is that of opioid induced hyperalgesia. This syndrome is manifest as enhanced pain, sensitivity and loss of analgesic efficacy in patients treated with opioids who actually become sensitized to painful stimuli. This article focuses on the treatment of burn pain and how current analgesic therapies with opioids may cause hyperalgesia and affect the adequacy of treatment for burn pain. This article also provides possible modalities to help therapeutically manage these patients and considers future analgesic strategies which may help to improve pain management in this complicated patient population.

A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.