Analgesic roles of peripheral intrinsic met-enkephalin and dynorphin A in long-lasting inflammatory pain induced by complete Freund's adjuvant in rats

Jiang, Yongliang; He, Xiaofen; Shen, Yilan; Yin, Xiaohu; Du, Junying; Liang, Yi; Fang, Jianqiao

doi:10.3892/etm.2015.2407

Cited by 22 publications

(16 citation statements)

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“…Formalin-induced mechanical secondary allodynia and hyperalgesia starts 1 day after injection and lasts at least 12 days [1,15,28,30]. CFA-induced tactile allodynia starts at 6 h [44] and lasts at least 18 days [33]. Formalin-induced sensitization was assessed 3 and 6 days after injection [1,2,44].…”

Section: Methodsmentioning

confidence: 99%

The α5 subunit containing GABAA receptors contribute to chronic pain

Bravo‐Hernández

Corleto

Barragán-Iglesias

et al. 2016

Pain

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It has been recently proposed that α5-subunit containing GABAA receptors (α5-GABAA receptors) that mediate tonic inhibition might be involved in pain. The purpose of this study was to investigate the contribution of α5-GABAA receptors in the loss of GABAergic inhibition and in formalin-, Complete Freund’s adjuvant (CFA)- and L5/L6 spinal nerve ligation-induced long-lasting hypersensitivity. Formalin or CFA injection and L5/L6 spinal nerve ligation produced long-lasting allodynia and hyperalgesia. Moreover, formalin injection impaired the rate-dependent depression (RDD) of the Hofmann reflex. Peripheral and intrathecal pre-treatment or post-treatment with the α5-GABAA receptor antagonist, L-655,708 (0.15–15 nmol) prevented and reversed, respectively, these long-lasting behaviors. Formalin injection increased α5-GABAA receptors mRNA expression in the spinal cord and dorsal root ganglia (DRG) mainly at 3 days. α5-GABAA receptors were localized in the dorsal spinal cord and DRG co-labeling with NeuN, CGRP and IB4 suggesting their presence in peptidergic and non-peptidergic neurons. These receptors were found mainly in small- and medium-size neurons. Formalin injection enhanced α5-GABAA receptors fluorescence intensity in spinal cord and DRG at 3 and 6 days. Intrathecal administration of L-655,708 (15 nmol) prevented and reversed formalin-induced impairment of RDD. These results suggest that α5-GABAA receptors play a role in the loss of GABAergic inhibition and contribute to long-lasting secondary allodynia and hyperalgesia.

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Section: Methodsmentioning

confidence: 99%

The α5 subunit containing GABAA receptors contribute to chronic pain

Bravo‐Hernández

Corleto

Barragán-Iglesias

et al. 2016

Pain

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“…TRPV1 is likely the best-characterized sensory transducer expressed in polymodal C fibers, which process both thermal and mechanical hyperalgesia during long-lasting inflammation (31). Using the CFA model of chronic inflammatory pain, we evaluated peripheral immune-derived endogenous opioid antinociception (6,(32)(33)(34)(35) in WT and TRPV1 −/− mice by measuring paw withdrawal threshold (PWT) during the acute and later (resolution) phase of inflammation. In WT animals, PWT was decreased by 50% at day 4 after intraplantar injection of CFA, and animals started to recover at day 6.…”

Section: Trpv1 Stimulates Endogenous Opioid-mediated Analgesia Duringmentioning

confidence: 99%

TRPV1 promotes opioid analgesia during inflammation

et al. 2019

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Pain and inflammation are inherently linked responses to injury, infection, or chronic diseases. Given that acute inflammation in humans or mice enhances the analgesic properties of opioids, there is much interest in determining the inflammatory transducers that prime opioid receptor signaling in primary afferent nociceptors. Here, we found that activation of the transient receptor potential vanilloid type 1 (TRPV1) channel stimulated a mitogen-activated protein kinase (MAPK) signaling pathway that was accompanied by the shuttling of the scaffold protein β-arrestin2 to the nucleus. The nuclear translocation of β-arrestin2 in turn prevented its recruitment to the μ-opioid receptor (MOR), the subsequent internalization of agonist-bound MOR, and the suppression of MOR activity that occurs upon receptor desensitization. Using the complete Freund’s adjuvant (CFA) inflammatory pain model to examine the role of TRPV1 in regulating endogenous opioid analgesia in mice, we found that naloxone methiodide (Nal-M), a peripherally restricted, nonselective, and competitive opioid receptor antagonist, slowed the recovery from CFA-induced hypersensitivity in wild-type, but not TRPV1-deficient, mice. Furthermore, we showed that inflammation prolonged morphine-induced antinociception in a mouse model of opioid receptor desensitization, a process that depended on TRPV1. Together, our data reveal a TRPV1-mediated signaling pathway that serves as an endogenous pain-resolution mechanism by promoting the nuclear translocation of β-arrestin2 to minimize MOR desensitization. This previously uncharacterized mechanism may underlie the peripheral opioid control of inflammatory pain. Dysregulation of the TRPV1–β-arrestin2 axis may thus contribute to the transition from acute to chronic pain.

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“…All tests were performed by an experimenter blinded to the treatment groups. To evaluate thermal hyperalgesia, PWL was measured by a plantar tester (Ugo Basile 37370, Italy) as in our previous studies (Fang et al, 2013b;Jiang et al, 2015). After acclimatizing the rats for 30 min in a clear plastic chamber, a stimulus of radiant heat (high-intensity projector lamp bulb) was placed under the glass floor directly beneath the hind paws.…”

Section: Measurement Of Pwlmentioning

confidence: 99%