Pain
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Comparative Study
Peripheral group II metabotropic glutamate receptors mediate endogenous anti-allodynia in inflammation.
We previously demonstrated that activation of peripheral group II mGluRs inhibits PGE2-induced thermal hyperalgesia. In the present study we examined the role of peripheral group II mGluRs in inflammation-induced mechanical allodynia in CD1 mice. Subcutaneous injection of group II mGluR agonists or antagonists into the plantar surface of the mouse hind paw did not alter mechanical thresholds, suggesting that peripheral group II mGluRs did not modulate basal mechanical sensation. ⋯ The application of group II mGluR antagonist (LY341495) alone delayed the recovery of PGE2- and carrageenan-induced mechanical allodynia. Three hours after injection of carrageenan, LY341495-injected mice showed little or no recovery with mechanical thresholds 8+/-1% of pre-carrageenan baselines, compared to 57+/-8% of pre-carrageenan baselines in vehicle-injected mice at the same time point. Our results suggest that activation of peripheral group II mGluRs reduces inflammation-induced mechanical allodynia and that peripheral group II mGluRs may mediate endogenous anti-allodynia effects, which speed recovery from inflammation-induced hypersensitivity.
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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 Comparative Study Clinical Trial
The association between anger expression and chronic pain intensity: evidence for partial mediation by endogenous opioid dysfunction.
Recent work suggests that an expressive anger management style (anger-out) is associated with elevated acute pain sensitivity due to endogenous opioid antinociceptive dysfunction. We tested the hypothesis that this opioid dysfunction mediates the previously reported positive association between anger-out and chronic pain intensity. To assess endogenous opioid antinociception in the laboratory, 71 subjects with chronic low back pain received opioid blockade (8 mg naloxone i.v.) or placebo in counterbalanced order in separate sessions. ⋯ Inclusion of blockade effects in the first step of the regression resulted in a decrease from 7 to 3% in chronic pain variance accounted for by anger-out. Opioid dysfunction did not mediate the positive association between anger-in and chronic pain. These results provide preliminary support for the hypothesis that the positive association between anger expression and chronic pain intensity is mediated by opioid antinociceptive system dysfunction.
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To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. ⋯ There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy.
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Comparative Study
Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables.
Laboratory pain research has been criticized as being irrelevant to the clinical experience of pain. Previous findings have been inconsistent with some studies suggesting that experimental pain responses may be related to the reported presence or severity of chronic pain, while others report no such associations. However, few of these studies assess a variety of laboratory pain responses, and none has assessed relationships between clinical pain and diffuse noxious inhibitory controls (DNIC) in healthy subjects. ⋯ Of the laboratory pain variables, only DNIC was the sole consistent predictor of clinical pain and physical health, with greater DNIC responses related to less pain, better physical functioning, and better self-rated health. In addition, age differences in DNIC appeared to partially mediate age differences in physical functioning. These findings highlight the potential clinical relevance of experimental pain procedures and suggest that DNIC may be the laboratory pain response most closely associated with clinical pain and health-related variables.