Abstract
Resiniferatoxin is an ultrapotent capsaicin analog that mediates nociceptive processing; treatment with resiniferatoxin can cause an inflammatory response and, ultimately, neuropathic pain. Hepatoma-derived growth factor, a growth factor related to normal development, is associated with neurotransmitters surrounding neurons and glial cells. Therefore, the study aims to investigate how blocking hepatoma-derived growth factor affects the inflammatory response in neuropathic pain. Serum hepatoma-derived growth factor protein expression was measured via ELISA. Resiniferatoxin was administrated intraperitoneally to induce neuropathic pain in 36 male Sprague-Dawley rats which were divided into three groups (resiniferatoxin+recombinant hepatoma-derived growth factor antibody group, resiniferatoxin group, and control group) (n = 12/group). The mechanical threshold response was tested with calibration forceps. Cell apoptosis was measured by TUNEL assay. Immunofluorescence staining was performed to detect apoptosis of neuron cells and proliferation of astrocytes in the spinal cord dorsal horn. RT-PCR technique and western blot were used to measure detect inflammatory factors and protein expressions. Serum hepatoma-derived growth factor protein expression was higher in the patients with sciatica compared to controls. In resiniferatoxin-group rats, protein expression of hepatoma-derived growth factor was higher than controls. Blocking hepatoma-derived growth factor improved the mechanical threshold response in rats. In dorsal root ganglion, blocking hepatoma-derived growth factor inhibited inflammatory cytokines. In the spinal cord dorsal horn, blocking hepatoma-derived growth factor inhibited proliferation of astrocyte, apoptosis of neuron cells, and attenuated expressions of pain-associated proteins. The experiment showed that blocking hepatoma-derived growth factor can prevent neuropathic pain and may be a useful alternative to conventional analgesics.
Highlights
After peripheral nerve degeneration, nociceptive input was reduced and neuropathic pain was developed
A global analysis that integrated proteome analysis revealed that a lack of hepatoma-derived growth factor (HDGF) genes can limit apoptosis induced by tumor necrosis factor α (TNF-α) [11]
The rat model of neuropathy used in this study showed that RTX injections decreased the mechanical threshold for pain, upregulated TNF-α inflammation in the dorsal root ganglion (DRG), and upregulated expressions of HDGF, PI3K, pAkt/Akt, TrkB, iNOS, and substance P in the spinal cord
Summary
Nociceptive input was reduced and neuropathic pain was developed. By affecting nociceptive nerves with small-diameter, some patients with peripheral nerve diseases have paradoxical symptoms such as neuropathic pain combined with skin denervation that reduces sensitivity to noxious stimuli [3, 4]. It is unclear whether injury to only small neurons can cause this paradoxical combination of reduced neuropathic pain and nociception. This study used a rat model of neuropathic pain to investigate whether treatment with the ultrapotent capsaicin analog resiniferatoxin (RTX) induces paradoxical changes in mechanical sensitivities [7, 8]. Unmyelinated nerves degeneration together with denervation of skin is the main feature of RTX-induced neuropathy [9], which is a precursor of pure small-fiber neuropathy and a good model of neuropathic pain. A global analysis that integrated proteome analysis revealed that a lack of hepatoma-derived growth factor (HDGF) genes can limit apoptosis induced by TNF-α [11]
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