Pain
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Episodic migraine (EM) may evolve into the more disabling chronic migraine (CM, monthly migraine days ≥ 8 and headache days ≥ 15) with unknown mechanism. Aiming to elucidate the pathophysiology of CM and its relationship with EM, this study characterized the visual cortical responses in CM and EM. Neuromagnetic visual-evoked responses to left-hemifield checkerboard reversals were obtained in patients with EM (interictal or ictal states), CM (interictal) and age-matched controls. ⋯ These CM features also characterized the P100m in the ictal state of EM (n=9). There was no difference of P100m between CM and ictal state of EM. In conclusion, patients with CM demonstrate a persistent ictal-like excitability pattern of the visual cortex between migraine attacks which may implicate central inhibitory dysfunction.
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Comparative Study
A novel mechanism of inhibition of high-voltage activated calcium channels by α-conotoxins contributes to relief of nerve injury-induced neuropathic pain.
α-Conotoxins that are thought to act as antagonists of nicotinic acetylcholine receptors (nAChRs) containing α3-subunits are efficacious in several preclinical models of chronic pain. Potent interactions of Vc1.1 with other targets have suggested that the pain-relieving actions of α-conotoxins might be mediated by either α9α10 nAChRs or a novel GABA(B) receptor-mediated inhibition of N-type calcium channels. Here we establish that three α-conotoxins, Vc1.1, AuIB and MII have distinct selectivity profiles for these three potential targets. ⋯ However, MII, a potent α3β2 nAChR antagonist but inactive on α9α10 and α3β4 nAChRs and GABA(B)/Ca(2+) channels, was demonstrated to have short-acting anti-allodynic action. This suggests that α3β2 nAChRs may also contribute to reversal of allodynia. Together, these findings suggest that inhibition of α9α10 nAChR is neither necessary nor sufficient for relief of allodynia and establish that α-conotoxins selective for GABA(B) receptor-dependent inhibition of N-type Ca(2+) channels relieve allodynia, and could therefore be developed to manage chronic pain.
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It was previously reported that in 5 patients with small-fiber neuropathy, neuropathic pain, and hyperalgesia, application of a single, brief electrical stimulus to the skin could give rise to 2 afferent impulses in a C-nociceptor fiber. These double spikes, which are attributed to unidirectional conduction failure at branch points in the terminal arborisation, provide a possible mechanism for hyperalgesia. We here report that similar multiple spikes are regularly observed in 3 rat models of neuropathic pain: nerve crush, nerve suture, and chronic constriction injury. ⋯ Whereas only double spikes had previously been described in patients, in these more extensive recordings from rats we found that triple spikes could also be observed after a single electrical stimulus. The results strengthen the suggestion that multiple spiking, because of impaired conduction in the terminal branches of nociceptors, may contribute to hyperalgesia in patients with neuropathic pain. Double and triple spikes in c-nociceptors, caused by impaired conduction in terminal branches, may be an important cause of hyperalgesia in patients with neuropathic pain.
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We examined the relationship between catastrophizing and a 3-stage model of pain processing, consisting of pain sensation intensity (stage 1), pain unpleasantness (stage 2), and suffering (stage 3). We studied 310 patients with chronic and severe osteoarthritic knee pain (68.7% female) using 4 competing structural equation models. A strong relationship was found between the suffering construct and its indicators. ⋯ These results emphasize the benefit of integrating knowledge of the psychological and neural mechanisms of pain. Catastrophizing makes a unique contribution to suffering apart from the contribution of immediate unpleasantness. The study results emphasize the benefit of integrating knowledge of the psychological and neural mechanisms of pain, and the importance of psychological intervention targeting catastrophizing to reduce pain-related suffering.