Articles: hyperalgesia.
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The Journal of physiology · Jul 2011
TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity.
The mechanosensory role of TRPA1 and its contribution to mechanical hypersensitivity in sensory neurons remains enigmatic. We elucidated this role by recording mechanically activated currents in conjunction with TRPA1 over- and under-expression and selective pharmacology. First, we established that TRPA1 transcript, protein and functional expression are more abundant in smaller-diameter neurons than larger-diameter neurons, allowing comparison of two different neuronal populations. ⋯ In summary our data demonstrate TRPA1 makes a contribution to normal mechanosensation in a specific subset of DRG neurons. Furthermore, they also provide new evidence illustrating mechanisms by which sensitisation or over-expression of TRPA1 enhances nociceptor mechanosensitivity. Overall, these findings suggest TRPA1 has the capacity to tune neuronal mechanosensitivity depending on its degree of activation or expression.
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Neuroscience letters · Jul 2011
Minocycline injection in the ventral posterolateral thalamus reverses microglial reactivity and thermal hyperalgesia secondary to sciatic neuropathy.
We hypothesized that microglia in the ventral posterolateral (VPL) nucleus of the thalamus are reactive following peripheral nerve injury, and that inhibition of microglia by minocycline injection in the VPL attenuates thermal hyperalgesia. Our results show increased expression of OX-42 co-localized with phosphorylated p38MAPK (P-p38) in the VPL seven days after chronic constriction injury (CCI) of the sciatic nerve. ⋯ Minocycline abrogates the increased expression of OX-42 in the VPL after CCI. Therefore, peripheral nerve injury favors a hyperactive microglial phenotype in the VPL, suggesting remote neuroimmune signaling from the damaged nerve to the brain, concomitant with neuropathic behavior that is reversed by local intervention in the VPL to inhibit microglia.
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Platinum-based anticancer drugs cause neurotoxicity. In particular, oxaliplatin produces early-developing, painful, and cold-exacerbated paresthesias. However, the mechanism underlying these bothersome and dose-limiting adverse effects is unknown. ⋯ Administration of cisplatin evoked mechanical allodynia, an effect that was reduced in TRPA1-deficient mice. TRPA1 is therefore required for oxaliplatin-evoked mechanical and cold hypersensitivity, and contributes to cisplatin-evoked mechanical allodynia. Channel activation is most likely caused by glutathione-sensitive molecules, including reactive oxygen species and their byproducts, which are generated after tissue exposure to platinum-based drugs from cells surrounding nociceptive nerve terminals.
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Electrical high-frequency stimulation (HFS) of skin afferents elicits long-term potentiation (LTP)-like hyperalgesia in humans. Time courses were evaluated in the facilitating (homotopic) or facilitated (heterotopic) pathways to delineate the relative contributions of early or late LTP-like pain plasticity. HFS in healthy subjects (n=55) elicited highly significant pain increases to electrical stimuli via the conditioning electrode (to 145% of control, homotopic pain LTP) and to pinprick stimuli in adjacent skin (to 190% of control, secondary hyperalgesia). ⋯ Dynamic mechanical allodynia (only present in 16 of 55 subjects) lasted for a shorter time than secondary hyperalgesia. Three different readouts of nociceptive central sensitization suggest that brief intense nociceptive input elicits early LTP1 of pain sensation (based on posttranslational modifications), but susceptible subjects may already develop longer-lasting late LTP2 (based on transcriptional modifications). These findings support the hypothesis that LTP may contribute to the development of persistent pain disorders.
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One indirect line of evidence for opioid-induced hyperalgesia (OIH) in humans is decreased pain thresholds (PTREs) and tolerances (PTOLs) in opioid addicts on opioids. There are a number of such studies in opioid maintained addicts, but no such studies in chronic pain patients (CPPs) with current opioid addiction. The objective of this study was to determine if this group demonstrates hyperalgesia. ⋯ This study contributes to the human OIH literature. However, because of the potential confounders in this study, the issue of OIH in humans remains unresolved.