European journal of pain : EJP
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Randomized Controlled Trial
Validating speed of onset as a key component of good analgesic response in acute pain.
Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief, as well as need for additional analgesia. ⋯ In acute pain following third molar extraction, faster acting analgesic formulations provide earlier onset of pain relief, better overall pain relief and a less frequent need for additional analgesia, indicating longer lasting pain relief.
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In postherpetic neuralgia (PHN), dorsal root ganglia neurons are damaged. According to the proposed models, PHN pain might be associated with nociceptive deafferentation, and peripheral (heat hyperalgesia) or central sensitization (allodynia). ⋯ PHN is associated with damage of afferent fibres. Central sensitization (i.e., allodynia) might contribute to PHN pain. There was a striking association between anxiety, depression and age, and the magnitude of PHN pain.
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Mounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo. ⋯ Here we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation.
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Inflammatory mediators activate and sensitize nociceptors. Tissue acidosis with low pH of 5.5 often accompanies inflammation and could enhance inflammatory pain and sensitization. ⋯ Our results confirm nociceptor class independent heat sensitization by PGE2 which is probably mediated by transient receptor potential vanilloid 1 phosphorylation. However, prolonged and increased pain responses in humans upon low pH/PGE2 stimulation appear to be primarily dependent on CMi fibres, whereas CM nociceptors appear crucial for phasic responses.
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Previous data showed that, in rats, anti-migraine drugs (triptans, olcegepant) significantly reduced mechanical allodynia induced by infraorbital nerve (ION) ligation but not that evoked by sciatic nerve (SN) ligation. Whether this also occurs with MK-8825, a novel anti-migraine drug also acting through CGRP receptor blockade (but chemically unrelated to olcegepant) was tested in the present study, which also investigated possible anti-neuroinflammatory effects of this drug. ⋯ These data further support the idea that CGRP receptor blockade might be a valuable approach to alleviate trigeminal, but not spinal, neuropathic pain through, at least partly, an inhibitory effect on neuropathic pain-associated increase in NO production in trigeminal ganglion.