Sex differences in kappa opioid receptor inhibition of latent postoperative pain sensitization in dorsal horn
| Autor: | Bradley K. Taylor, Renee R. Donahue, Bret N. Smith, Lilian Custodio-Patsey, Joshua Lambert, Weisi Fu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Spinal Cord Dorsal Horn Pyrrolidines Receptors Opioid mu κ-opioid receptor Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Sex Factors Naltrindole Internal medicine Receptors Opioid delta Medicine Animals Extracellular Signal-Regulated MAP Kinases Sensitization Endogenous opioid Pharmacology Pain Postoperative business.industry Receptors Opioid kappa Naltrexone Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Endocrinology Opioid Hyperalgesia Benzamides Itching Female medicine.symptom μ-opioid receptor business Somatostatin 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropharmacology |
| ISSN: | 1873-7064 |
| Popis: | Tissue injury produces a delicate balance between latent pain sensitization (LS) and compensatory endogenous opioid receptor analgesia that continues for months, even after re-establishment of normal pain thresholds. To evaluate the contribution of mu (MOR), delta (DOR), and/or kappa (KOR) opioid receptors to the silencing of chronic postoperative pain, we performed plantar incision at the hindpaw, waited 21 days for the resolution of hyperalgesia, and then intrathecally injected subtype-selective ligands. We found that the MOR-selective inhibitor CTOP (1–1000 ng) dose-dependently reinstated mechanical hyperalgesia. Two DOR-selective inhibitors naltrindole (1–10 μg) and TIPP[Ψ] (1–20 μg) reinstated mechanical hyperalgesia, but only at the highest dose that also produced itching, licking, and tail biting. Both the prototypical KOR-selective inhibitors nor-BNI (0.1–10 μg) and the newer KOR inhibitor with more canonical pharmocodynamic effects, LY2456302 (0.1–10 μg), reinstated mechanical hyperalgesia. Furthermore, LY2456302 (10 μg) increased the expression of phosphorylated signal-regulated kinase (pERK), a marker of central sensitization, in dorsal horn neurons but not glia. Sex studies revealed that LY2456302 (0.3 μg) reinstated hyperalgesia and pERK expression to a greater degree in female as compared to male mice. Our results suggest that spinal MOR and KOR, but not DOR, maintain LS within a state of remission to reduce the intensity and duration of postoperative pain, and that endogenous KOR but not MOR analgesia is greater in female mice. |
| Databáze: | OpenAIRE |
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