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.

1.
Stübgen JP: Interferon alpha and neuromuscular disorders. J Neuroimmunol 2009;207:3–17.
2.
Blalock JE: The syntax of immune-neuroendocrine communication. Immunol Today 1994;15:504–511.
3.
Dafny N: Is interferon-α a neuromodulator? Brain Res Brain Res Rev 1998;26:1–15.
4.
Jiang CL, Lu CL, Liu XY: The molecular basis for bidirectional communication between the immune and neuroendocrine systems. Domest Anim Endocrinol 1998;15:363–369.
5.
McCann SM, Kimura M, Karanth S, Yu WH, Rettori V: Role of nitric oxide in the neuroendocrine responses to cytokines. Ann NY Acad Sci 1998;840:174–184.
6.
Jiang CL, Son LX, Lu CL, You ZD, Wang YX, Sun LY, Cui RY, Liu XY: Analgesic effect of interferon-alpha via mu opioid receptor in the rat. Neurochem Int 2000;36:193–196.
7.
Wang JY, Zeng XY, Fan GX, Yuan YK, Tang JS: µ- but not δ- and ĸ-opioid receptor mediates the nucleus submedius interferon-α-evoked antinociception in the rat. Neurosci Lett 2006;397:254–258.
8.
Blalock JE, Smith EM: Human leukocyte interferon: structural and biological relatedness to adrenocorticotropic hormone and endorphins. Proc Natl Acad Sci USA 1980;77:5972–5974.
9.
Lee JK, Park SH, Sim YB, Jung JS, Suh HW: Interaction of supraspinally administered interferon-α with opioid system in the production of antinociception. Arch Pharm Res 2010;33:1059–1063.
10.
Ataka T, Kumamoto E, Shimoji K, Yoshimura M: Baclofen inhibits more effectively C-afferent than Aδ-afferent glutamatergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices. Pain 2000;86:273–282.
11.
Bird GC, Han JS, Fu Y, Adwanikar H, Willis WD, Neugebauer V: Pain-related synaptic plasticity in spinal dorsal horn neurons: role of CGRP. Mol Pain 2006;2:31.
12.
Zhong YQ, Li KC, Zhang X: Potentiation of excitatory transmission in substantia gelatinosa neurons of rat spinal cord by inhibition of estrogen receptor alpha. Mol Pain 2010;6:92.
13.
Li KC, Zhang FX, Li CL, Wang F, Yu MY, Zhong YQ, Zhang KH, Lu YJ, Wang Q, Ma XL, Yao JR, Wang JY, Lin LB, Han M, Zhang YQ, Kuner R, Xiao HS, Bao L, Gao X, Zhang X: Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase. Neuron 2011;69:974–987.
14.
Zhang X, Bao L, Guan JS: Role of delivery and trafficking of δ-opioid peptide receptors in opioid analgesia and tolerance. Trends Pharmacol Sci 2006;27:324–329.
15.
Zhang X, Bao L, Shi TJ, Ju G, Elde R, Hökfelt T: Down-regulation of µ-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy. Neuroscience 1998;82:223–240.
16.
Guan JS, Xu ZZ, Gao H, He SQ, Ma GQ, Sun T, Wang LH, Zhang ZN, Lena I, Kitchen I, Elde R, Zimmer A, He C, Pei G, Bao L, Zhang X: Interaction with vesicle luminal protachykinin regulates surface expression of δ-opioid receptors and opioid analgesia. Cell 2005;122:619–631.
17.
Bao L, Jin SX, Zhang C, Wang LH, Xu ZZ, Zhang FX, Wang LC, Ning FS, Cai HJ, Guan JS, Xiao HS, Xu ZQ, He C, Hökfelt T, Zhou Z, Zhang X: Activation of delta opioid receptors induces receptor insertion and neuropeptide secretion. Neuron 2003;37:121–133.
18.
Lombard MC, Besse D, Besson JM: Opioid receptors in the superficial layers of the rat spinal cord: functional implications in pain processing. Prog Brain Res 1995;104:77–92.
19.
Quirion R: Pain, nociception and spinal opioid receptors. Prog Neuropsychopharmacol Biol Psychiatry 1984;8:571–579.
20.
Mogil JS, Grisel JE, Hayward MD, Bales JR, Rubinstein M, Belknap JK, Low MJ: Disparate spinal and supraspinal opioid antinociceptive responses in β-endorphin-deficient mutant mice. Neuroscience 2000;101:709–717.
21.
Pinto M, Sousa M, Lima D, Tavares I: Participation of µ-opioid, GABA(B), and NK1 receptors of major pain control medullary areas in pathways targeting the rat spinal cord: implications for descending modulation of nociceptive transmission. J Comp Neurol 2008;510:175–187.
22.
Tseng LF: Evidence for ε-opioid receptor-mediated β-endorphin-induced analgesia. Trends Pharmacol Sci 2001;22:623–630.
23.
Wu HE, Thompson J, Sun HS, Leitermann RJ, Fujimoto JM, Tseng LF: Nonopioidergic mechanism mediating morphine-induced antianalgesia in the mouse spinal cord. J Pharmacol Exp Ther 2004;310:240–246.
24.
Wang HB, Zhao B, Zhong YQ, Li KC, Li ZY, Wang Q, Lu YJ, Zhang ZN, He SQ, Zheng HC, Wu SX, Hökfelt TG, Bao L, Zhang X: Coexpression of δ- and µ-opioid receptors in nociceptive sensory neurons. Proc Natl Acad Sci USA 2010;107:13117–13122.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.