Pain
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Research has shown that transcranial magnetic stimulation (TMS) results in a transient reduction in the experience of chronic pain. The present research aimed to investigate whether a single session of high frequency TMS is able to change the sensory thresholds of individuals suffering from chronic pain. ⋯ In contrast, no change in detection and pain thresholds was obtained following sham rTMS. The finding that rTMS can have a direct effect on sensory thresholds in individuals suffering from chronic pain has implications for the therapeutic use of rTMS in the relief of chronic pain.
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Comparative Study
Contribution of the ventromedial hypothalamus to generation of the affective dimension of pain.
The ventromedial hypothalamus (VMH) is a core structure underlying the generation of affective behaviors to threats. The prototypical threat to an individual is exposure to a noxious stimulus and the dorsomedial division of the VMH (dmVMH) receives nociceptive input. The present study evaluated the contribution of the dmVMH to generation of the affective reaction to pain in rats. ⋯ These treatments did not alter thresholds of other tailshock elicited responses (vocalizations during tailshock or spinal motor reflexes). Bicuculline and muscimol administered into the dmVMH also elevated and lowered the asymptotic level of fear conditioning supported by dmVMH stimulation or tailshock. These findings demonstrate that the dmVMH contributes to the processing of pain affect and that the affective dimension of pain belongs to a broader class of sensory experience that represents threat to the individual.
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Comparative Study
Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states.
Antisense (AS) oligodeoxynucleotides (ODNs) targeting the Nav 1.8 sodium channel have been reported to decrease inflammatory hyperalgesia and L5/L6 spinal nerve ligation-induced mechanical allodynia in rats. The present studies were conducted to further characterize Nav 1.8 AS antinociceptive profile in rats to better understand the role of Nav 1.8 in different pain states. Consistent with earlier reports, chronic intrathecal Nav 1.8 AS, but not mismatch (MM), ODN decreased TTX-resistant sodium current density (by 60.5+/-10.2% relative to MM; p<0.05) in neurons from L4 to L5 dorsal root ganglia and significantly attenuated mechanical allodynia following intraplantar complete Freund's adjuvant. ⋯ Finally, Nav 1.8 AS, but not MM, ODN treatment produced a small but significant attenuation of acute noxious mechanical sensitivity in naïve animals (17.6+/-6.2% effect, p<0.05 vs. MM). These data demonstrate a greater involvement of Nav 1.8 in frank nerve injury and inflammatory pain as compared to acute, post-operative or chemotherapy-induced neuropathic pain states.
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Important mechanisms that regulate inhibitory and facilitatory effects on TRPV1-mediated nociception are desensitization and phosphorylation, respectively. Using Ca2+-imaging, we have previously shown that desensitization of TRPV1 upon successive capsaicin applications was reversed by protein kinase C activation in dorsal root ganglion neurons and CHO cells. Here, using both Ca2+-imaging and patch-clamp methods, we show that PMA-induced activation of PKCepsilon is essential for increased sensitivity of desensitized TRPV1. ⋯ We also show that the expression level of PKCepsilon paralleled the amount of phosphorylated TRPV1 protein using an antibody specific for phosphorylated TRPV1 at S800. Furthermore, the anti-phosphoTRPV1 antibody detected phosphorylation of TRPV1 in mouse and rat DRG neurons and may be useful for research regarding nociception in native tissues. This study, therefore, identifies PKCepsilon and S800 as important therapeutic targets that may help regulate inhibitory effects on TRPV1 and hence its desensitization.
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Editorial Comment Comparative Study
Disrupted central somatosensory processing in CRPS: a unique characteristic of the syndrome?