Mol Pain
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cGMP-dependent kinase-I (cGKI) is known to regulate spinal pain processing. This enzyme consists of two isoforms (cGKIα and cGKIβ) that show distinct substrate specificity and tissue distribution. It has long been believed that the α isoform is exclusively expressed in the adult dorsal root ganglion. ⋯ In contrast, cGKIβ expression was upregulated in both the injured and uninjured dorsal root ganglions. Also, injury-induced cGKIβ upregulation was found to occur in small-to-medium-diameter dorsal root ganglion neurons. These data thus demonstrate the existence of two differently distributed cGKI isoforms in the dorsal root ganglion, and may provide insight into the cellular and molecular mechanisms of pain.
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Background Chronic pain is a persistent unpleasant sensation that produces pathological synaptic plasticity in the central nervous system. Both human imaging study and animal studies consistently demonstrate that the anterior cingulate cortex is a critical cortical area for nociceptive and chronic pain processing. Thus far, the mechanisms of excitatory synaptic transmission and plasticity have been well characterized in the anterior cingulate cortex for various models of chronic pain. ⋯ Importantly, protein expression of vesicular GABA transporter was reduced within the presynpase of the anterior cingulate cortex in complete Freund adjuvant model. In contrast, the complete Freund adjuvant model did not change the protein levels of GABAA receptors subunits such as α1, α5, β2, γ2, and δ. Conclusion Our results suggest that the induction phase of inflammatory pain involves spontaneous GABAergic plasticity at presynaptic terminals of the anterior cingulate cortex.
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Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (fa/fa) rats develop type 2 diabetes spontaneously with aging and show nociceptive hypersensitivity at the age of 13 weeks. In preclinical and clinical studies, the treatment of diabetic neuropathy is challenging, but complementary medicine such as transcutaneous auricular vagus nerve stimulation (taVNS) appears beneficial to the relief of neuropathic pain. ⋯ We conclude that daily 30-min taVNS sessions lessen diabetic neuropathy development by enhancing serotonergic function in genetically diabetes prone individuals. Perspective This article presents taVNS as a new approach to inhibit the development of diabetic neuropathy in genetically prone individuals. This approach could potentially help clinicians who seek to avoid the complication of neuropathic pain in diabetic patient or to relieve the pain if there was one.
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Comparative Study
A comparison of early and late treatments on allodynia and its chronification in experimental neuropathic pain.
Background Surgeries causing nerve injury can result in chronic neuropathic pain, which is clinically managed by using antidepressant or anticonvulsant drugs. Currently, there is a growing interest for investigating preemptive treatments that would prevent this long-term development of neuropathic pain. Our aim was to compare analgesic drugs using two distinct treatment modalities: either treatment onset at surgery time or following a couple of weeks of neuropathic pain. ⋯ When treatments started at day 25 postsurgery, desipramine, duloxetine, and anticonvulsants suppressed the mechanical allodynia. Conclusions Our data show that allodynia measured in experimental neuropathic pain model likely results from a combination of different processes (early vs. late allodynia) that display different sensitivity to treatments. We also propose that early anticonvulsant treatment with gabapentin or carbamazepine may have a prophylactic effect on the chronification of allodynia following nerve injury.
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The medial prefrontal cortex is involved in the process of sensory discrimination. In this study, we examined the local field potential activity response to the different stages of pain in the prelimbic cortex (PrL) which is a sub-region of the medial prefrontal cortex. Recent studies revealed extensive information about neural oscillations, but there is limited information on the local field potential profiles for acute or chronic pain, particularly in freely moving animals. ⋯ Delta oscillation was decreased by chronic pain and gamma oscillation varied with time. However, acute mechanical pain stimulus had no effects on local field potential in rats under mechanical allodynia. Together, our findings provide novel insights into the role of medial prefrontal cortex local field potential activity response to pain stimulus.