Articles: hyperalgesia-pathology.
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Background Although the peripheral and central sensitizations of trigeminal nervous system may be one of the important factors of migraine, the precise mechanism is not fully understood. In this study, we examined the influence of the sensitization of the second division of the trigeminal nerve (V2) by chronic constriction injury (CCI) of the infraorbital nerve (ION) on migraine headache, using the capsaicin-induced migraine model. Methods Male Sprague-Dawley rats were assigned to four groups: (a) sham surgery and topical-dural vehicle application (Sham + Vehicle) group, (b) CCI-ION and topical-dural vehicle application (CCI-ION + Vehicle) group, (c) sham surgery and topical-dural capsaicin application (Sham + Capsaicin) group, (d) CCI-ION and topical-dural capsaicin application (CCI-ION + Capsaicin) group. ⋯ However, comparing between effects of the peripheral and central sensitizations (in the TG and TCC), from our results, peripheral sensitization would play a much less or not significant role. Conclusions These data demonstrate that the sensitization of V2 could influence the activation and the sensitization of the first division of the trigeminal nerve in the TCC, subsequently exacerbating pain sensation and pain-related behaviors. We have shown for the first time that the existence of the central sensitization of V2 can be an exacerbating factor for migraine related nociceptive thresholds/activation.
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Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. ⋯ Hyperalgesia induced by spinal nerve ligation corresponds temporally and in magnitude with degranulation of thalamic mast cells. Here, we provide evidence that hyperalgesia induced by NGF, formalin and dynorphin also may depend on mast cell degranulation in the CNS whereas cromolyn, a mast cell stabilizer, blocks these effects in mice.
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Tactile allodynia, a condition in which innocuous mechanical stimuli are perceived as painful, is a common feature of chronic pain. However, how the brain reorganizes in relation to the emergence of tactile allodynia is still largely unknown. This may stem from the fact that experiments in humans are cross-sectional in nature, whereas animal brain imaging studies typically require anaesthesia rendering the brain incapable of consciously sensing or responding to pain. ⋯ In contrast, nucleus accumbens and prefrontal brain areas displayed abnormal activity to normally innocuous stimuli when such stimuli induced tactile allodynia at 28 days after peripheral nerve injury, which had not been the case at 5 days after injury. Our data indicate that tactile allodynia-related nociceptive inputs are not observable in the primary somatosensory cortex BOLD response. Instead, our data suggest that, in time, tactile allodynia differentially engages neural circuits that regulate the affective and motivational components of pain.
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Background Calpain is a calcium-dependent cysteine protease, and inhibition of calpain by pre-treatment with MDL28170 attenuated the rat mechanical allodynia in a variety of pain models. Postherpetic neuralgia (Shingles) is a neuropathic pain conditioned with the presence of profound mechanical allodynia. Systemic injection of resiniferatoxin can reproduce the clinical symptoms of postherpetic neuralgia. ⋯ Conclusions Up-regulation and activation of µ-calpain located in Schwann cell may be the mechanism underlying resiniferatoxin-mediated proteolysis of myelin basic protein in dorsal root. Calpain inhibitor MDL28170 prevents resiniferatoxin-induced sprouting of myelinated afferent fibers and mechanical allodynia through inhibition of degradation of the myelin basic protein in dorsal root. Our results indicate that inhibition of pathological µ-calpain activation may present an interesting novel drug target in the treatment of postherpetic neuralgia.