Pain
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While spontaneous and stimulus-evoked pain are the hallmarks of complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy, autonomic abnormalities, motor dysfunction, and trophic changes in the affected limb are additional clinical characteristics distinguishing this syndrome. Even though the exact underlying mechanisms of the syndrome remain obscure, a recent hypothesis suggests that the abnormal response of neural nociceptive tissue plays a major role in the pathogenesis of CRPS via the mechanism known as 'neurogenic inflammation'. The group of patients presented here exhibited all the clinical characteristics of CRPS but had no pain, thereby indicating that ongoing or evoked pain is not a necessary condition for CRPS to be maintained. We suggest the term complex regional painless syndrome to describe this syndrome.
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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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Randomized Controlled Trial Clinical Trial
Effects of TENS frequency, intensity and stimulation site parameter manipulation on pressure pain thresholds in healthy human subjects.
This study evaluated the effects of varying frequency, intensity and stimulation site, of transcutaneous electrical nerve stimulation (TENS) in an experimental model of pain. In a double-blind design 240 volunteers were randomised to one of six experimental TENS groups, a sham TENS or control (n=30 per group; gender balanced). Two TENS frequencies (110 or 4 Hz) and two intensities (strong but comfortable or highest tolerable) at a fixed pulse duration (200 micros) were applied at three sites relative to the measurement site (segmentally, extrasegmentally or a combination of these), for 30 min. Pressure pain thresholds (PPT) were measured using a pressure algometer, in the first dorsal interosseous muscle, every 10 min, during stimulation and for a further 30 min. The high frequency, high intensity segmental, and combined stimulation groups, showed rapid onset and significant hypoalgesic effects. This effect was sustained for 20 min post-stimulation in the high frequency segmental group. All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group, and none of these groups reached a clinically significant hypoalgesic level. ⋯ The role of TENS frequency, intensity and site are pivotal to achieving optimal hypoalgesic effects, during and after stimulation. Clinical applications of these parameter combinations require further investigations.