Articles: neuralgia.
-
One specific behavior can be synergistically modulated by different neural pathways. Medial septal (MS) cholinergic system innervates widespread cortical and subcortical regions and participates in pain modulation, but the underlying neural pathways are not fully understood. This study examined the contribution of MS cholinergic neurons and 2 neural pathways: MS-rostral anterior cingulate cortex (rACC) and MS-ventral hippocampal CA1 (vCA1), in modulating perceptual and affective pain behaviors in a mouse model of chronic inflammatory pain. ⋯ By contrast, chemogenetic activation of MS cholinergic neurons also produced analgesia, but by rescuing hypofunctional pyramidal neurons in vCA1. These results clearly demonstrate that the MS cholinergic system differentially modulates chronic inflammatory pain through MS-rACC or MS-vCA1 pathways. More significantly, our research provides evidence for a novel paradigm of neural circuit modulation: MS cholinergic inhibition and activation induce similar analgesia but through distinct neural pathways.
-
The neurochemical effects of adenosine signaling in small-fiber neuropathy leading to neuropathic pain are yet to be explored in a direct manner. This study examined this system at the level of ligand (through the ectonucleotidase activity of prostatic acid phosphatase [PAP]) and adenosine A1 receptors (A1Rs) in resiniferatoxin (RTX) neuropathy, a peripheral neurodegenerative disorder that specifically affects nociceptive nerves expressing transient receptor potential vanilloid type 1 (TRPV1). We conducted immunohistochemistry on dorsal root ganglion (DRG) neurons, high-performance liquid chromatography for functional assays, and pharmacological interventions to alter PAP and A1Rs in mice with RTX neuropathy. ⋯ Furthermore, A1Rs were downregulated (P = 0.002), and this downregulation was colocalized with the TRPV1 receptor (31.0% ± 2.8%). Mechanical allodynia was attenuated in a dose-dependent response by i.t. injection of the A1R ligand, adenosine; however, no analgesia was evident when an exogenous adenosine was blocked by A1R antagonist. This study demonstrated dual mechanisms of neuropathic pain in TRPV1-induced neuropathy, involving a reduced adenosine system at both the ligand (adenosine) and receptor (A1Rs) levels.
-
Glial cells play important roles in the development and maintenance of neuropathic pain. In particular, activated microglia in the spinal cord facilitate the hyper-excitability of dorsal horn neurons after peripheral nerve injury via pro-inflammatory molecules. In this study, we investigated the possible involvement of the anti-inflammatory cytokine, interleukin-4 (IL-4), in neuropathic pain. ⋯ Intrathecal administration of recombinant IL-4 suppressed mechanical hypersensitivity in neuropathic rats, and the analgesic effect of IL-4 was accompanied by further enhancement of pSTAT6 expression in spinal microglia. Taken together, these results suggest that the adaptive responses of microglia to nerve injury involve both inflammatory and anti-inflammatory signaling, including IL-4R alpha and pSTAT6. These findings support that utilizing the endogenous anti-nociceptive activity of IL-4R alpha may modify the cell lineage of pro-nociceptive microglia, thus providing a novel therapeutic strategy for neuropathic pain.
-
Neurodegeneration is associated with changes in basal cellular function due to the dysregulation of autophagy. A recent study introduced the involvement of autophagy during spinal nerve ligation (SNL). Nefopam has shown potential for reducing neuropathic pain, but the underlying mechanisms are unknown. Here, we investigated the effects of nefopam on neuropathic pain development following SNL, focusing on the involvement of autophagy. ⋯ Collectively, the mode of action of nefopam on neuropathic pain appears to be associated with downregulation of phospho-JNK and autophagy, as well as modulation of the immune response.
-
Braz. J. Med. Biol. Res. · Jul 2018
Transcriptomic differential lncRNA expression is involved in neuropathic pain in rat dorsal root ganglion after spared sciatic nerve injury.
Dorsal root ganglia (DRG) neurons regenerate spontaneously after traumatic or surgical injury. Long noncoding RNAs (lncRNAs) are involved in various biological regulation processes. Conditions of lncRNAs in DRG neuron injury deserve to be further investigated. ⋯ A total of 26 novel lncRNAs were found. Known lncRNA gene rno-Cntnap2 and novel lncRNA AC111653.1 were involved in neuropathic pain of DRGs after spared sciatic nerve injury. They contributed to peripheral nerve regeneration via the putative mechanisms.