| Autor: |
Walwyn, Wendy M., Wenling Chen, Hyeyoung Kim, Minasyan, Ani, Ennes, Helena S., McRoberts, James A., Marvizón, Juan Carlos G. |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 1/6/2016, Vol. 36 Issue 1, p204-221, 18p |
| Abstrakt: |
Many chronic pain disorders alternate between bouts of pain and periods of remission. The latent sensitization model reproduces this in rodents by showing that the apparent recovery ("remission") from inflammatory or neuropathic pain can be reversed by opioid antagonists. Therefore, this remission represents an opioid receptor-mediated suppression of a sustained hyperalgesic state. To identify the receptors involved, we induced latent sensitization in mice and rats by injecting complete Freund's adjuvant (CFA) in the hindpaw. InWT mice, responses to mechanical stimulation returned to baseline 3 weeks after CFA. In μ-opioid receptor (MOR) knock-out (KO) mice, responses did not return to baseline but partially recovered from peak hyperalgesia. Antagonists of α2A-adrenergic and δ-opioid receptors reinstated hyperalgesia inWTmice and abolished the partial recovery from hyperalgesia inMORKOmice. In rats, antagonists ofα2A adrenergic and μ-,δ-, and κ-opioid receptors reinstated hyperalgesia during remission from CFA-induced hyperalgesia. Therefore, these four receptors suppress hyperalgesia in latent sensitization.Wefurther demonstrated that suppression of hyperalgesia byMORswas due to their constitutive activity because of the following: (1) CFA-induced hyperalgesia was reinstated by theMORinverse agonist naltrexone (NTX), but not by its neutral antagonist 6β-naltrexol; (2) pro-enkephalin, pro-opiomelanocortin, and pro-dynorphin KO mice showed recovery from hyperalgesia and reinstatement by NTX; (3) there was no MOR internalization during remission; (4) MORs immunoprecipitated from the spinal cord during remission had increased Ser375 phosphorylation; and (5) electrophysiology recordings from dorsal root ganglion neurons collected during remission showed constitutive MOR inhibition of calcium channels. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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