Pain
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Pain is a biologically relevant signal and response to bodily threat, associated with the urge to restore the integrity of the body. Immediate protective responses include increased arousal, selective attention, escape, and facial expressions, followed by recuperative avoidance and safety-seeking behaviors. To facilitate early and effective protection against future bodily threat or injury, learning takes place rapidly. ⋯ In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, context dependent and only occurs through inhibitory processes. Here, we review features of associative forms of learning in humans that contribute to pain, pain-related distress, and disability and discuss promising future directions. Although conditioning has a long and honorable history, a conditioning perspective still might open new windows on novel treatment modalities that facilitate the well-being of individuals with chronic pain.
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Research into complex regional pain syndrome (CRPS) has made significant progress. First, there was the implementation of the official IASP "Budapest" diagnostic criteria. It would be desirable to also define exclusion and outcome criteria that should be reported in studies. ⋯ In an attempt to avoid pain, patients neglect their limb and learn maladaptive nonuse. The final step will be to assess large cohorts and to analyze these data together with data from public resources using a bioinformatics approach. We could then develop diagnostic toolboxes for individual pathophysiology and select focused treatments or develop new ones.
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Cancer pain sends a message. It is frightening to the patient. It heralds progression or recurrence to the oncologist. ⋯ In this manner, these nerves serve as bellwethers and sensors embedded within the cancer. When we rigorously assess patients' cancer pain, we gain insight into the action of cancer. An enhanced understanding of cancer pain offers biological questions that if answered might not only provide relief from cancer pain but might also improve survival.
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Neuropathic pain (NP) is a significant medical and socioeconomic burden. Epidemiological surveys have indicated that many patients with NP do not receive appropriate treatment for their pain. A number of pharmacological agents have been found to be effective in NP on the basis of randomized controlled trials including, in particular, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor antidepressants, pregabalin, gabapentin, opioids, lidocaine patches, and capsaicin high-concentration patches. ⋯ However, meta-analyses indicate that only a minority of patients with NP have an adequate response to drug therapy. Several reasons may account for these findings, including a modest efficacy of the active drugs, a high placebo response, the heterogeneity of diagnostic criteria for NP, and an inadequate classification of patients in clinical trials. Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms.
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Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. ⋯ Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.