Chronic morphine treatment enhances sciatic nerve stimulation-induced immediate early gene expression in the rat dorsal horn
Synaptic plasticity is a property of neurons that can be induced by conditioning electrical stimulation (CS) of afferent fibers in the spinal cord. This is a widely studied property of spinal cord and hippocampal neurons. CS has been shown to trigger enhanced expression of immediate early gene proteins (IEGPs), with peak increases observed 2 hour post stimulation. Chronic morphine treatment has been shown to promoteinduce opioid-induced hyperalgesia, and also to increase CS-induced central sensitization in the dorsal horn. As IEGP expression may contribute to development of chronic pain states, we aimed to determine whether chronic morphine treatment affects the expression of IEGPs following sciatic nerve CS. Changes in expression of the IEGPs Arc, c-Fos or Zif268 were determined in cells of the lumbar dorsal horn of the spinal cord. Chronic Morphine pretreatment over 7 days led to a significant increase in the number of IEGP positive cells observed at both 2 h and 6 h after CS. The same pattern of immunoreactivity was obtained for all IEGPs, with peak increases occurring at 2 h post CS. In contrast, morphine treatment alone in sham operated animals had no effect on IEGP expression. We conclude that chronic morphine treatment enhances stimulus-induced expression of IEGPs in the lumbar dorsal horn. These data support the notion that morphine alters gene expression responses linked to nociceptive stimulation and plasticity.
- Bojovic O, Panja D, Bittins M, Bramham CR, Tjolsen A (2015) Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats. PLoS One 10: e0123604.
- Bramham CR, Alme MN, Bittins M, Kuipers SD, Nair RR, Pai B, Panja D, Schubert M, Soule J, Tiron A, Wibrand K (2010) The Arc of synaptic memory. Exp Brain Res 200: 125-140.
- Caudle RM, Mannes AJ (2000) Dynorphin: friend or foe?. Pain 87: 235-239.
- Cole AJ, Saffen DW, Baraban JM, Worley PF (1989) Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activa¬tion. Nature 340: 474-476.
- Corvello CM, Metz R, Bravo R, Armelin MC (1995) Expression and characterization of mouse cFos protein using the baculovirus expression system: ability to form functional AP-1 complex with coexpressed cJun protein. Cell Mol Biol Res 41: 527-535.
- Delander GE, Schott E, Brodin E, Fredholm BB (1997) Spinal expression of mRNA for immediate early genes in a model of chronic pain. Acta Physiol Scand 161: 517¬525.
- Fry JP, Herz A, Zieglgansberger W (1980) A demonstration of naloxone-precipitated opiate withdrawal on single neu¬rones in the morphine-tolerant/dependent rat brain. Br J Pharmacol 68: 585-592.
- Fukazawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38: 447-460.
- Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA (2000) Inhibition of activity-dependent arc protein expression in the rat hip¬pocampus impairs the maintenance of long-term potentia¬tion and the consolidation of long-term memory. J Neurosci 20: 3993-4001.
- Harris JA (1998) Using c-fos as a neural marker of pain. Brain Res Bull 45: 1-8.
- Haugan F, Rygh LJ, Tjolsen A (2008a) Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats. Acta Anaesthesiol Scand 52: 681-687.
- Haugan F, Wibrand K, Fiska A, Bramham CR, Tjolsen A (2008b) Stability of long term facilitation and expression of zif268 and Arc in the spinal cord dorsal horn is modu¬lated by conditioning stimulation within the physiological frequency range of primary afferent fibers. Neuroscience 154: 1568-1575.
- Heinricher MM, Tavares I, Leith JL, Lumb BM (2009) Descending control of nociception: Specificity, recruit¬ment and plasticity. Brain Res Rev 60: 214-225.
- Hossaini M, Jongen JL, Biesheuvel K, Kuhl D, Holstege JC (2010) Nociceptive stimulation induces expression of Arc/Arg3.1 in the spinal cord with a preference for neu¬rons containing enkephalin. Mol Pain 6: 43.
- Hunt SP, Pini A, Evan G (1987) Induction of c-fos-like pro¬tein in spinal cord neurons following sensory stimulation. Nature 328: 632-634.
- Jones MW, Errington ML, French PJ, Fine A, Bliss TV, Garel S, Charnay P, Bozon B, Laroche S, Davis S (2001) A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci 4: 289-296.
- Kaczmarek L (2000) Gene expression in learning processes. Acta Neurobiol Exp (Wars) 60: 419-424.
- Knapska E, Kaczmarek L (2004) A gene for neuronal plas¬ticity in the mammalian brain: Zif268/Egr-1/NGFI-A/ Krox-24/TIS8/ZENK?. Prog Neurobiol 74: 183-211.
- Korb E, Wilkinson CL, Delgado RN, Lovero KL, Finkbeiner S (2013) Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity. Nat Neurosci 16: 874-883.
- Kullmann DM, Lamsa KP (2007) Long-term synaptic plas¬ticity in hippocampal interneurons. Nat Rev Neurosci 8: 687-699.
- Laughlin TM, Vanderah TW, Lashbrook J, Nichols ML, Ossipov M, Porreca F, Wilcox GL (1997) Spinally admin¬istered dynorphin A produces long-lasting allodynia: involvement of NMDA but not opioid receptors. Pain 72: 253-260.
- Liu X, Sandkuhler J (1997) Characterization of long-term potentiation of C-fiber-evoked potentials in spinal dorsal horn of adult rat: essential role of NK1 and NK2 recep¬tors. J Neurophysiol 78: 1973-1982.
- Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H (2004) Structural basis of long-term potentiation in single den¬dritic spines. Nature 429: 761-766.
- Messaoudi E, Kanhema T, Soule J, Tiron A, Dagyte G, da Silva B, Bramham CR (2007) Sustained Arc/Arg3.1 syn¬thesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo. J Neurosci 27: 10445-10455.
- Munglani R, Hunt SP (1995) Molecular biology of pain. Br J Anaesth 75: 186-192.
- Myrum C, Baumann A, Bustad HJ, Flydal MI, Mariaule V, Alvira S, Cuellar J, Haavik J, Soule J, Valpuesta JM, Marquez JA, Martinez A, Bramham CR (2015) Arc is a flexible modular protein capable of reversible self-oli- gomerization. Biochem J 468: 145-158.
- Okuno H, Akashi K, Ishii Y, Yagishita-Kyo N, Suzuki K, Nonaka M, Kawashima T, Fujii H, Takemoto-Kimura S, Abe M, Natsume R, Chowdhury S, Sakimura K, Worley PF, Bito H (2012) Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIbeta. Cell 149: 886-898.
- Otahara N, Ikeda T, Sakoda S, Shiba R, Nishimori T (2003) Involvement of NMDA receptors in Zif/268 expression in the trigeminal nucleus caudalis following formalin injec¬tion into the rat whisker pad. Brain Res Bull 62: 63-70.
- Panja D, Bramham CR (2014) BDNF mechanisms in late LTP formation: A synthesis and breakdown. Neuropharmacology 76 Pt C: 664-676.
- Panja D, Kenney JW, D'Andrea L, Zalfa F, Vedeler A, Wibrand K, Fukunaga R, Bagni C, Proud CG, Bramham CR (2014) Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF- TrkB signaling to MNK. Cell Rep 9: 1430-1445.
- Plath N, Ohana O, Dammermann B, Errington ML, Schmitz D, Gross C, Mao X, Engelsberg A, Mahlke C, Welzl H, Kobalz U, Stawrakakis A, Fernandez E, Waltereit R, Bick-Sander A, Therstappen E, Cooke SF, Blanquet V,
- Wurst W, Salmen B, Bosl MR, Lipp HP, Grant SG, Bliss TV, Wolfer DP, Kuhl D (2006) Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron 52: 437-444.
- Robbins A, Schmitt D, Winterson BJ, Meng ID (2012) Chronic morphine increases Fos-positive neurons after concurrent cornea and tail stimulation. Headache 52: 262-273.
- Rohde DS, Detweiler DJ, Basbaum AI (1996) Spinal cord mechanisms of opioid tolerance and dependence: Fos- like immunoreactivity increases in subpopulations of spinal cord neurons during withdrawal [corrected]. Neuroscience 72: 233-242.
- Rohde DS, Detweiler DJ, Basbaum AI (1997) Formalin- evoked Fos expression in spinal cord is enhanced in morphine-tolerant rats. Brain res 766: 93-100.
- Rygh LJ, Suzuki R, Rahman W, Wong Y, Vonsy JL, Sandhu H, Webber M, Hunt S, Dickenson AH (2006) Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. Eur J Neurosci 24: 761-772.
- Shepherd JD, Rumbaugh G, Wu J, Chowdhury S, Plath N, Kuhl D, Huganir RL, Worley PF (2006) Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA recep¬tors. Neuron 52(3): 475-484.
- Sukhatme VP, Cao XM, Chang LC, Tsai-Morris CH, Stamenkovich D, Ferreira PC, Cohen DR, Edwards SA, Shows TB, Curran T, et al. (1988) A zinc finger-encoding gene coregulated with c-fos during growth and differen¬tiation, and after cellular depolarization. Cell 53: 37-43.
- Svendsen F, Tjolsen A, Hole K (1997) LTP of spinal A beta and C-fibre evoked responses after electrical sciatic nerve stimulation. Neuroreport 8: 3427-3430.
- Vanderah TW, Laughlin T, Lashbrook JM, Nichols ML, Wilcox GL, Ossipov MH, Malan TP, Jr., Porreca F (1996) Single intrathecal injections of dynorphin A or des-Tyr- dynorphins produce long-lasting allodynia in rats: block¬ade by MK-801 but not naloxone. Pain 68: 275-281.
- Wang JQ, Daunais JB, McGinty JF (1994) NMDA receptors mediate amphetamine-induced upregulation of zif/268 and preprodynorphin mRNA expression in rat striatum. Synapse 18: 343-353.