Informace o publikaci
Priming and Signal Transduction of Delta Opioid Receptors in Dorsal Root Ganglia Neurons in a Mouse Experimental Model of Neuropathic Pain - Utilizing Immunohistochemical Detection to Elucidate Intracellular Processes
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| Rok publikování | 2024 |
| Druh | Konferenční abstrakty |
| Citace | |
| Popis | Delta opioid receptor (DOR) agonists are promising for the peripheral treatment of neuropathic pain without serious adverse side effects. However, DOR is functionally inactive for antinociceptive signaling under basal conditions. Tissue damage or exposure to inflammatory mediators can convert DOR from a nonresponsive state to a functionally competent state. Based on our previous results, a nerve injury results in increased inflammatory mediators in the primary sensory neurons (PSNs). We used mouse a spared nerve injury model with unilateral spared tibial nerve (SNIt) to study the intraneuronal localization of DOR protein in PSNs. We utilized double immunofluorescence staining for DOR with WGA, GRK2, ?-arrestin2, EEA1, and Rab7 to visualize intraneuronal DOR trafficking and verify some hypotheses regarding its intraneuronal fate. The results demonstrated that DOR immunofluorescence (-IF) is predominantly present in large-diameter PSNs of naive mice, and SNIt resulted in increased DOR-IF in all types of PSNs. Double immunostaining confirmed the localization of DOR in the plasma membrane of PSNs together with GRK2, which was reduced by the SNIt. Naive and uninjured PSNs displayed ?-arrestin2-IF concentrated in a ring at the superficial region of the neurons without colocalization with DOR-IF. SNIt induced scattered ?-arrestin2-IF, which was colocalized with DOR-IF. Increased DOR-IF was detected intraneuronally in early endosomes (EEA1+) following SNIt compared with naive controls, but limited DOR-IF was present in late endosomes (Rab7+). In conclusion, SNIt, as a mouse model of neuropathic pain, induced an increased level of DOR in the plasma membrane and predominantly in early endosomes of PSNs. Reduced colocalization of DOR with GRK2 may indicate the functional competence of DOR in the bodies of PSNs after SNIt. |
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