Pain
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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
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 characteristics of spatial summation of pressure pain are not clear. Pressure pain threshold (PPT) and perceived pressure pain intensity were measured in the hand, painfree back and myofascial trigger points (MTPs) in the back, using three different stimulus areas (0.5, 1 and 2 cm(2)). PPT decreased and perceived pain increased significantly with an increase in stimulation area in all the regions (e.g. ⋯ In conclusion, both PPT and perceived pressure pain intensity are subject to a considerable spatial summation in all the regions tested. The quality of pressure-evoked pain is probably determined by this spatial summation. Body region significantly affects the PPT level for a fixed stimulation area but not the magnitude of its spatial summation for areas up to 2 cm(2), which are probably within the receptive field of single spinal nociceptive neurons.
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In painful inflammation, exogenous as well as endogenous corticotropin-releasing hormone (CRH) can release opioid peptides (mainly beta-endorphin) from various types of immune cells and produce antinociception by activating opioid receptors on peripheral sensory nerve endings. CRH mediates its central effects through two high-affinity membrane receptors, the CRH receptor subtypes 1 and 2. It is unclear at present whether the peripheral antinociceptive effects of CRH are mediated through CRH receptor 1 (CRH R1) or CRH receptor 2 (CRH R2). ⋯ Also we observed a high degree of co-localization of CRH R1 and CRH R2 receptors on circulating and resident immune cells. Both the selective CRH R1 antagonist CP-154,526 and the selective CRH R2 antagonist astressin 2B significantly attenuated peripheral antinociceptive effects of CRH indicating the involvement of both CRH receptor subtypes. Taken together, these findings suggest that in inflammatory pain CRH-induced peripheral antinociception is mediated via both CRH R1 and CRH R2 located on END containing immune cells within inflamed sites.
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Randomized Controlled Trial Clinical Trial
Pain coping strategies play a role in the persistence of pain in post-herpetic neuralgia.
Post-herpetic neuralgia (PHN) is a neuropathic pain state that is often difficult to treat. Although frequently discussed in the clinical literature, little is known about the impact of pain on daily function and the extent to which psychosocial factors, in particular pain coping strategies, influence adaptation to this chronic illness. In the context of a crossover pharmacological trial, 68 patients with PHN completed a battery of psychological measures during a first drug-free baseline period. ⋯ Patients who reported increasing their activity in response to pain also reported more perceived interference due to pain 8 weeks later. Higher levels of ignoring pain sensations at baseline were prospectively correlated with more depressive symptoms 8 weeks later. These findings support a role for the continued investigation of cognitive-behavioral factors affecting the adaptation of elderly individuals experiencing PHN.