Pain
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Clinical Trial
Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.
Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. ⋯ Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted.
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Comparative Study
Genotype-dependence of gabapentin and pregabalin sensitivity: the pharmacogenetic mediation of analgesia is specific to the type of pain being inhibited.
The antiepileptic drug, gabapentin, and another structurally related compound, pregabalin, are increasingly employed in the pharmacotherapy of chronic pain states, although their primary mechanism of action remains a topic of active study. A genomic approach to the study of these drugs may elucidate their potentially novel mechanisms. We examined the heritability of sensitivity to analgesia from gabapentin and pregabalin as a precursor to linkage mapping efforts. ⋯ However, there was virtually no correlation between strain sensitivities to pregabalin inhibition of formalin nociception and zymosan thermal hyperalgesia. In light of previous data from our laboratory and others regarding morphine analgesia, we now establish and empirically demonstrate the general principle that pharmacogenetic mechanisms underlying analgesic sensitivity are specific to the type of pain being inhibited. This has considerable implications for ongoing pharmacogenetic investigations and, more generally, for the choices of preclinical models of pain used in drug development.
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The use of percentage pain reduction is increasingly used to evaluate the effectiveness of pain treatments, but the degree of agreement between calculated percentage pain reduction (CPPR) as calculated from pre- and post-treatment levels of pain intensity and those reported directly by patients is unknown. Lack of agreement between these two measures could lead to errors in the determination of treatment effectiveness. We aimed to determine the agreement between CPPR and patient-reported percentage pain reduction (PRPPR). ⋯ The agreement between percentage pain reductions calculated from NRS scores and those estimated by patients did not vary according to gender or age. The good overall agreement between percentage pain reductions calculated from NRS scores and those estimated by patients suggests that these indices may be used interchangeably. The findings of this study extend existing patient-centered pain research and may be applied for the evaluation and comparison of pain treatments.
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Cancer-induced bone pain is a major clinical problem. A rat model based on intra-tibial injection of MRMT-1 mammary tumour cells was used to mimic progressive cancer-induced bone pain. At the time of stable behavioural changes (decreased thresholds to mechanical and cold stimuli) and bone destruction, in vivo electrophysiology was used to characterize natural (mechanical, thermal, and cold) and electrical-evoked responses of superficial and deep dorsal horn neurones in halothane-anaesthetized rats. ⋯ Deep WDR neurones showed less pronounced changes to the superficial dorsal horn, however, the response to thermal and electrical stimuli, but not mechanical, were significantly increased in the MRMT-1-injected rats. In conclusion, the spinal cord is significantly hyperexcitable with previously superficial NS cells becoming responsive to wide-dynamic range stimuli possibly driving this plasticity via ascending and descending facilitatory pathways. The alterations in superficial dorsal horn neurones have not been reported in neuropathy or inflammation adding to the evidence for cancer-induced bone pain reflecting a unique pain state.
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Comparative Study
The development of psychological changes following whiplash injury.
Psychological distress is a feature of chronic whiplash-associated disorders, but little is known of psychological changes from soon after injury to either recovery or symptom persistence. This study prospectively measured psychological distress (General Health Questionnaire 28, GHQ-28), fear of movement/re-injury (TAMPA Scale of Kinesphobia, TSK), acute post-traumatic stress (Impact of Events Scale, IES) and general health and well being (Short Form 36, SF-36) in 76 whiplash subjects within 1 month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered (<8), mild pain and disability (10-28) or moderate/severe pain and disability (>30). ⋯ Elevated IES scores, indicative of a moderate post-traumatic stress reaction, were unique to the group with moderate/severe symptoms. The results of this study demonstrated that all those experiencing whiplash injury display initial psychological distress that decreased in those whose symptoms subside. Whiplash participants who reported persistent moderate/severe symptoms at 6 months continue to be psychologically distressed and are also characterised by a moderate post-traumatic stress reaction.