Effects of transgene-mediated endomorphin-2 in inflammatory pain
Shuanglin Hao
Department of Neurology and VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
These authors contributed equally to this work.
Search for more papers by this authorDarren Wolfe
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, United States
These authors contributed equally to this work.
Current address: Diamyd, Inc. Pittsburgh, PA, United States.
Search for more papers by this authorJoseph C. Glorioso
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, United States
Search for more papers by this authorMarina Mata
Department of Neurology and VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
Search for more papers by this authorCorresponding Author
David J. Fink
Department of Neurology and VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
Tel.: +1 734 936 9070; fax: +1 734 763 5059. [email protected]Search for more papers by this authorShuanglin Hao
Department of Neurology and VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
These authors contributed equally to this work.
Search for more papers by this authorDarren Wolfe
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, United States
These authors contributed equally to this work.
Current address: Diamyd, Inc. Pittsburgh, PA, United States.
Search for more papers by this authorJoseph C. Glorioso
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, United States
Search for more papers by this authorMarina Mata
Department of Neurology and VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
Search for more papers by this authorCorresponding Author
David J. Fink
Department of Neurology and VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
Tel.: +1 734 936 9070; fax: +1 734 763 5059. [email protected]Search for more papers by this authorCurrent address: Diamyd, Inc. Pittsburgh, PA, United States.
ABSTRACT
We examined the analgesic properties of endomorphin-2 expressed in DRG neurons transduced with a non-replicating herpes simplex virus (HSV)-based vector containing a synthetic endomorphin-2 gene construct. HSV-mediated endomorphin-2 expression reduced nocisponsive behaviors in response to mechanical and thermal stimuli after injection of complete Freund's adjuvant (CFA) into the paw, and reduced peripheral inflammation measured by paw swelling after injection of CFA. The analgesic effect of the vector was blocked by either intraperitoneal or intrathecal administration of naloxone methiodide, blocking peripheral and central μ opioid receptors, respectively. Endomorphin-2 vector injection also reduced spontaneous pain-related behaviors in the delayed phase of the formalin test and in both CFA and formalin models suppressed spinal c-fos expression. The magnitude of the vector-mediated analgesic effect on the delayed phase of the formalin test was similar in naïve animals and in animals with opiate tolerance induced by twice daily treatment with morphine, suggesting that there was no cross-tolerance between vector-mediated endomorphin-2 and morphine. These results suggest that transgene-mediated expression of endomorphin-2 in transduced DRG neurons in vivo acts both peripherally and centrally through mu opioid receptors to reduce pain perception.
References
- Bras J.M. Antunes, A.L. Epstein, S. Bourgoin, M. Hamon, F. Cesselin, M. Pohl Herpes simplex virus 1-mediated transfer of preproenkephalin A in rat dorsal root ganglia. J Neurochem 70 1998 1299.
- A. Barber Mu- and kappa-opioid receptor agonists produce peripheral inhibition of neurogenic plasma extravasation in rat skin. Eur J Pharmacol 236 1993 113.
- A.I. Basbaum, H.L. Fields Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7 1984 309.
- D. Besse, M.C. Lombard, J.M. Zajac, B.P. Roques, J.M. Besson Pre- and postsynaptic distribution of mu, delta and kappa opioid receptors in the superficial layers of the cervical dorsal horn of the rat spinal cord. Brain Res 521 1990a 15.
- D. Besse, M.C. Lombard, J.M. Zajac, B.P. Roques, J.M. Besson Pre- and postsynaptic location of mu, delta and kappa opioid receptors in the superficial layers of the dorsal horn of the rat spinal cord. Prog Clin Biol Res 328 1990b 183.
- E.A. Bolan, Y.X. Pan, G.W. Pasternak Functional analysis of MOR-1 splice variants of the mouse mu opioid receptor gene Oprm. Synapse 51 2004 11.
- S.E. Bove, S.L. Calcaterra, R.M. Brooker, C.M. Huber, R.E. Guzman, P.L. Juneau et al. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthritis Cartilage 11 2003 821.
- J. Braz, C. Beaufour, A. Coutaux, A.L. Epstein, F. Cesselin, M. Hamon et al. Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons. J Neurosci 21 2001 7881.
- G. Catheline, S. Le Guen, J.M. Besson Effects of opioid receptor antagonists on the effects of i.v. morphine on carrageenin evoked c-Fos expression in the superficial dorsal horn of the rat spinal cord. Brain Res 824 1999 105.
- G. Catheline, S. Le Guen, J.M. Besson Intravenous morphine does not modify dorsal horn touch-evoked allodynia in the mononeuropathic rat: a Fos study. Pain 92 2001 389.
- S.R. Chaplan, F.W. Bach, J.W. Pogrel, J.M. Chung, T.L. Yaksh Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53 1994 55.
- V. Chapman, A. Diaz, A.H. Dickenson Distinct inhibitory effects of spinal endomorphin-1 and endomorphin-2 on evoked dorsal horn neuronal responses in the rat. Br J Pharmacol 122 1997 1537.
- X. Chen, J. Li, M. Mata, J. Goss, D. Wolfe, J.C. Glorioso et al. Herpes simplex virus type 1 ICP0 protein does not accumulate in the nucleus of primary neurons in culture. J Virol 74 2000 10132.
- W.J. Dixon Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol 20 1980 441.
- J.R. Goss, M. Mata, W.F. Goins, H.H. Wu, J.C. Glorioso, D.J. Fink Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion. Gene Ther 8 2001 551.
- J.R. Goss, C.F. Harley, M. Mata, M.E. O'Malley, W.F. Goins, X.-P. Hu et al. Herpes vector-mediated expression of proenkephalin reduces pain-related behavior in a model of bone cancer pain. Ann Neurol 52 2002 662.
- S. Hao, O. Takahata, K. Mamiya, H. Iwasaki Sevoflurane suppresses noxious stimulus-evoked expression of Fos-like immunoreactivity in the rat spinal cord via activation of endogenous opioid systems. Life Sci 71 2002 571.
- S. Hao, M. Mata, W. Goins, J.C. Glorioso, D.J. Fink Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect. Pain 102 2003 135.
- S. Hao, M. Mata, J.C. Glorioso, D.J. Fink HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain. Mol Pain 2 2006 6.
- K. Hargreaves, R. Dubner, F. Brown, C. Flores, J. Joris A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32 1988 77.
- A.H. Hassan, A. Ableitner, C. Stein, A. Herz Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue. Neuroscience 55 1993 185.
- Z. Helyes, A. Szabo, J. Nemeth, B. Jakab, E. Pinter, A. Banvolgyi et al. Antiinflammatory and analgesic effects of somatostatin released from capsaicin-sensitive sensory nerve terminals in a Freund's adjuvant-induced chronic arthritis model in the rat. Arthritis Rheum 50 2004 1677.
- W.E. Hobbs IInd, N.A. De Luca Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0. J Virol 73 1999 8245.
- J. Joris, A. Costello, R. Dubner, K.M. Hargreaves Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia. Pain 43 1990 95.
- D. Julius, A.I. Basbaum Molecular mechanisms of nociception. Nature 413 2001 203.
- D.M. Krisky, D. Wolfe, W.F. Goins, P.C. Marconi, R. Ramakrishnan, M. Mata et al. Deletion of multiple immediate-early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther 5 1998 1593.
- D. Labuz, R. Przewlocki, B. Przewlocka Cross-tolerance between the different mu-opioid receptor agonists endomorphin-1, endomorphin-2 and morphine at the spinal level in the rat. Neurosci Lett 334 2002 127.
- J. Liu, D. Wolfe, S. Hao, S. Huang, J.C. Glorioso, M. Mata et al. Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. Mol Ther 10 2004 57.
- Q.P. Ma, C.J. Woolf Basal and touch-evoked fos-like immunoreactivity during experimental inflammation in the rat. Pain 67 1996 307.
- A. Mauborgne, O. Lutz, J.C. Legrand, M. Hamon, F. Cesselin Opposite effects of delta and mu opioid receptor agonists on the in vitro release of substance P-like material from the rat spinal cord. J Neurochem 48 1987 529.
- A. Meunier, A. Latremoliere, A. Mauborgne, S. Bourgoin, V. Kayser, F. Cesselin et al. Attenuation of pain-related behavior in a rat model of trigeminal neuropathic pain by viral-driven enkephalin overproduction in trigeminal ganglion neurons. Mol Ther 11 2005 608.
- G.W. Pasternak Incomplete cross tolerance and multiple mu opioid peptide receptors. Trends Pharmacol Sci 22 2001 67.
- G.W. Pasternak Multiple opiate receptors: deja vu all over again. Neuropharmacology 47 (Suppl. 1) 2004 312.
- M. Pohl, M.C. Lombard, S. Bourgoin, A. Carayon, J.J. Benoliel, A. Mauborgne et al. Opioid control of the in vitro release of calcitonin gene-related peptide from primary afferent fibres projecting in the rat cervical cord. Neuropeptides 14 1989 151.
- R.W. Presley, D. Menetrey, J.D. Levine, A.I. Basbaum Systemic morphine suppresses noxious stimulus-evoked fos protein-like immunoreactivity in the rat spinal cord. J Neurosci 10 1990 323.
- V. Puskovic, D. Wolfe, J. Goss, S. Huang, M. Mata, J.C. Glorioso et al. Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo. Mol Ther 10 2004 67.
- M. Schafer, Y. Imai, G.R. Uhl, C. Stein Inflammation enhances peripheral mu-opioid receptor-mediated analgesia, but not mu-opioid receptor transcription in dorsal root ganglia. Eur J Pharmacol 279 1995 165.
- J. Scholz, C.J. Woolf Can we conquer pain?. Nat Neurosci 5 (Suppl.) 2002 1062.
- C. Stein The control of pain in peripheral tissue by opioids. N Engl J Med 332 1995 1685.
- L.S. Stone, C.A. Fairbanks, T.M. Laughlin, H.O. Nguyen, T.M. Bushy, M.W. Wessendorf et al. Spinal analgesic actions of the new endogenous opioid peptides endomorphin −1 and −2. Neuroreport 8 1997 3131.
- S.P. Wilson, D.C. Yeomans, M.A. Bender, Y. Lu, W.F. Goins, J.C. Glorioso Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus. Proc Natl Acad Sci USA 96 1999 3211.
- D. Wolfe, S. Hao, J. Hu, R. Srinivasan, J. Goss, M. Mata et al. Engineering an endomorphin-2 gene for use in neuropathic pain therapy. Pain 133 2007 29.
- B.L. Wolozin, G.W. Pasternak Classification of multiple morphine and enkephalin binding sites in the central nervous system. Proc Natl Acad Sci USA 78 1981 6181.
- T.L. Yaksh Pharmacology and mechanisms of opioid analgesic activity. Acta Anaesthesiol Scand 41 1997 94.
- D.C. Yeomans, T. Jones, C.E. Laurito, Y. Lu, S.P. Wilson Reversal of ongoing thermal hyperalgesia in mice by a recombinant herpesvirus that encodes human preproenkephalin. Mol Ther 9 2004 24.
- D.C. Yeomans, Y. Lu, C.E. Laurito, M.C. Peters, G. Vota-Vellis, S.P. Wilson et al. Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia. Mol Ther 13 2006 589.
- J.E. Zadina, L. Hackler, L.J. Ge, A.J. Kastin A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386 1997 499.
- M. Zimmermann Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16 1983 109.
Citing Literature
