Analgesic effect of interferon-alpha via mu opioid receptor in the rat

Jiang, Chun‐Lei; Lee, Song; Lu, Cheng-Wei; You, Z.D; Wang, Y.X; Sun, Lihua; Cui, Rui-Yao; Liu, X.Y

doi:10.1016/s0197-0186(99)00124-2

Cited by 38 publications

(32 citation statements)

References 13 publications

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“…It has also been reported that IFN-· can bind to opioid receptors [7,8], and we provided further information that the analgesic effect of IFN-· was mediated by the Ì opioid receptor [9].…”

Section: Introductionsupporting

confidence: 70%

The Analgesic Domain of Interferon-α2b Contains an Essential Proline<sup>39</sup> Residue

Lee¹,

Chen²,

Jiang

2002

Neuroimmunomodulation

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Objective: It has been demonstrated that there are structural and functional similarities between interferon-α (INF-α) and endorphins. We have reported that there are distinct domains in the IFN-α molecule that mediate immune and analgesic effects, respectively, and that the opioid-like analgesic effect of IFN-α is mediated by the µ opioid receptor, thus inferring that the analgesic domain of IFN-α consists of Tyr¹²² and the residues around Tyr¹²² in the tertiary structure. The aim of this work was to further explore the molecular basis for the analgesic domain of IFN-α. Methods: By using site-directed mutagenesis, the structure of IFN-α was changed and a mutant of IFN-α was obtained. Then, the antiviral activity and opioid-like analgesic activity of IFN-α were measured. Results: When the Pro³⁹ residue of IFN-α, which is located close to the Tyr¹²² residue in the tertiary structure, was mutated to Gly, the analgesic activity of this mutant was lost completely, but the antiviral activity of IFN-α was maintained compared with wild-type IFN-α. Conclusions: Combining the sequence of the endomorphin, it is suggested that the Pro³⁹ residue is one of the constituents of the analgesic domain of IFN-α and contributes to IFN-α binding to the µ opioid receptor.

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Section: Introductionsupporting

confidence: 70%

The Analgesic Domain of Interferon-α2b Contains an Essential Proline<sup>39</sup> Residue

Lee¹,

Chen²,

Jiang

2002

Neuroimmunomodulation

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“…Cyclic D-phe-cys-Try-DTrp-Arg-Thr-Pen-Thr-NH 2 , a -OR antagonist, blocks the fever induced by IL-6 (Benamar et al, 2002). Pretreatment with naloxone inhibits the prolonged immobility time and analgesic effect induced by administration of interferon-␣ jpet.aspetjournals.org (Jiang et al, 2000a;Makino et al, 2000). The results suggest that the OR may play many more important roles than previously thought.…”

Section: Discussionmentioning

confidence: 74%

Cardioprotection of Interleukin-2 Is Mediated via κ-Opioid Receptors

Cao

Xia²,

Tu³

et al. 2004

J Pharmacol Exp Ther

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We examined whether interleukin-2 (IL-2) protects the myocardium against injury induced by ischemia and reperfusion via the -opioid receptor (OR). The cardioprotective effect of IL-2 was evaluated by measuring infarct size and lactate dehydrogenase (LDH) release in response to ischemia and reperfusion in the isolated rat heart. IL-2 at an optimal dose of 50 U/ml mimicked the effect of ischemic preconditioning by reducing infarct size and LDH release. The infarct and LDH-reducing effects of IL-2 were blocked by nor-binaltorphimine (5 M), a -OR antagonist, but not naltrindole (5 M), a ␦-OR antagonist known to block the action of its stimulation. Moreover, blockade of the mitochondrial ATP-sensitive potassium (mito-K ATP ) channel with a selective antagonist, 5-hydroxydecanoate (100 M), or a nonselective antagonist of K ATP channels, glybenclamide (100 M), or blockade of protein kinase C (PKC) with its inhibitors

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“…However, previous studies showed that intracerebral IFN-α, but not intrathecal IFN-α, had a antinociceptive effect in the tail-flick nociceptive behavior test [9]. This effect was mediated by the activation of µ-opioid receptors (MORs) or an interaction of β-endorphin-sensitive opioid receptors with MORs activated by IFN-α at the supraspinal level [6,7,9]. As we all known, the opioid system is critical for inhibitory modulation of pain transmission.…”

Section: Discussionmentioning

confidence: 99%

“…There are also many reports demonstrating that IFN-α participates in important functions of the nerve system and suggesting that IFN-α is a neuromodulator [2,3,4,5]. Several studies suggested that IFN-α played an important role in nociception [6,7]. Some studies have shown that IFN-α could bind to opioid receptors in vitro and cause potent endorphin-like opioid effects, including analgesia, lack of spontaneous locomotion and catalepsy after intracerebral injection into mice [8,9].…”

Section: Introductionmentioning

confidence: 99%

Interferon-Alpha Enhances Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord

Qin¹,

Hou²,

Fang³

et al. 2012

Neuroimmunomodulation

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Objective: It has been shown that interferon-α (IFN-α) is synthesized and secreted by macrophages, monocytes, T lymphocytes, glial cells and neurons. IFN-α has been shown to have an antinociceptive effect at the supraspinal level in the nerve system. However, it is unclear how IFN-α is involved in the modulation of nociceptive transmission in the spinal cord. Methods: In the present study, IFN-α was used to test the potential functional roles in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of IFN-α on substantia gelatinosa (SG) neurons in the dorsal root-attached spinal cord slice prepared from adult rats. Results: We found that IFN-α increased glutamatergic excitatory postsynaptic currents evoked by the stimulation of either Aδ or C afferent fibers. Further studies showed that IFN-α treatment dose-dependently increased spontaneous excitatory postsynaptic current frequency in SG neurons, while not affecting the amplitude. Moreover, intrathecal antibody of IFN-α could reduce nociceptive responses in formalin test. Conclusions: These results suggest that IFN-α presynaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive responses could be inhibited by IFN-α antibody in the formalin test. Thus, IFN-α enhances the nociceptive transmission, which contributes to the behavioral nociceptive responses.

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Analgesic effect of interferon-alpha via mu opioid receptor in the rat

Cited by 38 publications

References 13 publications

The Analgesic Domain of Interferon-α2b Contains an Essential Proline<sup>39</sup> Residue

The Analgesic Domain of Interferon-α2b Contains an Essential Proline<sup>39</sup> Residue

Cardioprotection of Interleukin-2 Is Mediated via κ-Opioid Receptors

Interferon-Alpha Enhances Excitatory Transmission in Substantia Gelatinosa Neurons of Rat Spinal Cord

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