2024
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
DUBOVÝ, Petr; Zdeněk ROKOSKÝ a Anna RÁBOVÁZákladní údaje
Originální název
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
Název česky
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
Název anglicky
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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Vydání
Morphology 2024, 55th International Congress of Czech Anatomical Society 60th Lojda Symposium on Histochemistry. 2024. 2024
Další údaje
Typ výsledku
Konferenční abstrakt
Utajení
není předmětem státního či obchodního tajemství
Označené pro přenos do RIV
Ne
ISBN
978-80-8187-146-7
Klíčová slova anglicky
Delta Opioid Receptors; Dorsal Root Ganglia; Neuropathic Pain
Příznaky
Mezinárodní význam
Změněno: 3. 2. 2025 15:38, prof. RNDr. Petr Dubový, CSc.
V originále
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 naïve 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. Naïve 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 naïve 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.
Anglicky
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 naïve 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. Naïve 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 naïve 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.
Návaznosti
| MUNI/A/1563/2023, interní kód MU |
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