Temporal and Spatial Changes of μ-Opioid Receptors in the Brain, Spinal Cord and Dorsal Root Ganglion in a Rat Lumbar Disc Herniation Model.
Animals
Behavior, Animal
Disease Models, Animal
Female
Ganglia, Spinal
/ metabolism
Intervertebral Disc Displacement
/ complications
Lumbar Vertebrae
Nucleus Accumbens
/ metabolism
Pain
/ etiology
Periaqueductal Gray
/ metabolism
Rats
Rats, Sprague-Dawley
Receptors, Opioid, mu
/ metabolism
Spinal Cord
/ metabolism
Time Factors
Journal
Spine
ISSN: 1528-1159
Titre abrégé: Spine (Phila Pa 1976)
Pays: United States
ID NLM: 7610646
Informations de publication
Date de publication:
15 Jan 2019
15 Jan 2019
Historique:
pubmed:
14
7
2018
medline:
21
5
2019
entrez:
14
7
2018
Statut:
ppublish
Résumé
Controlled, interventional, animal study. To investigate the spatial and temporal changes of μ-opioid receptor (MOR) expression in a rat lumbar disc herniation (LDH) model. MORs widely express in the peripheral and central nervous systems, and opioid drugs produce an analgesic effect through their activation. However, the efficacy of opioid drugs is sometimes inadequate in several pathological conditions of pain. MORs in the brain as well as the spinal cord (SC) and dorsal root ganglion (DRG) are thought to be associated with pain-related behavior, but the underlying mechanisms are not completely understood. In all, 91 adult female Sprague-Dawley rats were used. Autologous nucleus pulposus (NP) was applied onto the left L5 DRG in the NP group rats. Rats were divided into two surgical groups, the NP and the sham group. The von Frey test of left hind paw was performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. Immunohistochemistry and immunoblotting in the DRG, SC, Caudate putamen, nucleus accumbens (NAc) and periaqueductal grey matter were performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. The thresholds in the NP group were significantly lower than those in the sham group from day 2 onwards. At days 7 and 14, MOR expression in the injured-side SC and DRG were significantly lower than those in the sham group. At day 21, MOR in the NAc was significantly decreased compared to that in the sham group. Changes of MOR expression in the NAc, SC and DRG were associated with pain-related behavior. This result might show the underling pathogenesis of the resistance to MOR agonists in the patient with LDH. N/A.
Sections du résumé
STUDY DESIGN
METHODS
Controlled, interventional, animal study.
OBJECTIVE
OBJECTIVE
To investigate the spatial and temporal changes of μ-opioid receptor (MOR) expression in a rat lumbar disc herniation (LDH) model.
SUMMARY OF BACKGROUND DATA
BACKGROUND
MORs widely express in the peripheral and central nervous systems, and opioid drugs produce an analgesic effect through their activation. However, the efficacy of opioid drugs is sometimes inadequate in several pathological conditions of pain. MORs in the brain as well as the spinal cord (SC) and dorsal root ganglion (DRG) are thought to be associated with pain-related behavior, but the underlying mechanisms are not completely understood.
METHODS
METHODS
In all, 91 adult female Sprague-Dawley rats were used. Autologous nucleus pulposus (NP) was applied onto the left L5 DRG in the NP group rats. Rats were divided into two surgical groups, the NP and the sham group. The von Frey test of left hind paw was performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. Immunohistochemistry and immunoblotting in the DRG, SC, Caudate putamen, nucleus accumbens (NAc) and periaqueductal grey matter were performed before surgery, and 2, 7, 14, 21 and 28 days after surgery.
RESULTS
RESULTS
The thresholds in the NP group were significantly lower than those in the sham group from day 2 onwards. At days 7 and 14, MOR expression in the injured-side SC and DRG were significantly lower than those in the sham group. At day 21, MOR in the NAc was significantly decreased compared to that in the sham group.
CONCLUSION
CONCLUSIONS
Changes of MOR expression in the NAc, SC and DRG were associated with pain-related behavior. This result might show the underling pathogenesis of the resistance to MOR agonists in the patient with LDH.
LEVEL OF EVIDENCE
METHODS
N/A.
Identifiants
pubmed: 30005035
doi: 10.1097/BRS.0000000000002776
pii: 00007632-201901150-00003
doi:
Substances chimiques
Receptors, Opioid, mu
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
85-95Références
Blumberg H, Jänig W. Changes of reflexes in vasoconstrictor neurons supplying the cat hindlimb following chronic nerve lesions: a model for studying mechanisms of reflex sympathetic dystrophy? J Auton Nerv Syst 1983; 7:399–411.
Tahmoush AJ. Causalgia: redefinition as a clinical pain syndrome. Pain 1981; 10:187–197.
Aoki Y, Rydevik B, Kikuchi S, et al. Local application of disc-related cytokines on spinal nerve roots. Spine (Phila Pa 1976) 2002; 27:1614–1617.
Igarashi T, Kikuchi S, Shubayev V, et al. 2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine (Phila Pa 1976) 2000; 25:2975–2980.
Kawakami M, Tamaki T, Weinstein JN, et al. Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat. Spine (Phila Pa 1976) 1996; 21:2101–2107.
Kayama S, Konno S, Olmarker K, et al. Incision of the anulus fibrosus induces nerve root morphologic, vascular, and functional changes. An experimental study. Spine (Phila Pa 1976) 1996; 21:2539–2543.
McCarron RF, Wimpee MW, Hudkins PG, et al. The inflammatory effect of nucleus pulposus. A possible element in the pathogenesis of low-back pain. Spine (Phila Pa 1976) 1987; 12:760–764.
Olmarker K, Rydevik B, Nordborg C. Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine (Phila Pa 1976) 1993; 18:1425–1432.
Olmarker K, Brisby H, Yabuki S, et al. The effects of normal, frozen, and hyaluronidase-digested nucleus pulposus on nerve root structure and function. Spine (Phila Pa 1976) 1997; 22:471–476.
Olmarker K, Larsson K. Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. Spine (Phila Pa 1976) 1998; 23:2538–2544.
Otoshi K, Kikuchi S, Konno S, et al. The reactions of glial cells and endoneurial macrophages in the dorsal root ganglion and their contribution to pain-related behavior after application of nucleus pulposus onto the nerve root in rats. Spine (Phila Pa 1976) 2010; 35:10–17.
Kobayashi H, Kikuchi S, Konno S, et al. Interaction of 5-hydroxytryptamine and tumor necrosis factor-( to pain-related behavior by nucleus pulposus applied on the nerve root in rats. Spine (Phila Pa 1976) 2011; 36:210–218.
Krupkova O, Sekiguchi M, Klasen J, et al. Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats. Eur Cell Mater 2014; 28:372–386.
Hashizume H, Kawakami M, Yoshida M, et al. Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats. Spine (Phila Pa 1976) 2007; 32:315–320.
Kato K, Kikuchi S, Konno S, et al. Participation of 5-hydroxytryptamine in pain-related behavior induced by nucleus pulposus applied on the nerve root in rats. Spine (Phila Pa 1976) 2008; 33:1330–1336.
Kato K, Sekiguchi M, Kikuchi S, et al. The effect of a 5-HT2A receptor antagonist on pain-related behavior, endogenous 5-hydroxytryptamine production, and the expression 5-HT2A receptors in dorsal root ganglia in a rat lumbar disc herniation model. Spine (Phila Pa 1976) 2015; 40:357–362.
Brisby H, Byröd G, Olmarker K, et al. Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots. J Orthop Res 2000; 18:815–820.
Kawakami M, Tamaki T, Hashizume H, et al. The role of phospholipase A2 and nitric oxide in pain-related behavior produced by an allograft of intervertebral disc material to the sciatic nerve of the rat. Spine (Phila Pa 1976) 1997; 22:1074–1079.
Kawakami M, Matsumoto T, Kuribayashi K, et al. mRNA expression of interleukins, phospholipase A2, and nitric oxide synthase in the nerve root and dorsal root ganglion induced by autologous nucleus pulposus in the rat. J Orthop Res 1999; 17:941–946.
Matthes HW, Maldonado R, Simonin F, et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature 1996; 383:819–823.
Zollner C, Shaqura MA, Bopaiah CP, et al. Painful inflammation-induced increase in mu-opioid receptor binding and G-protein coupling in primary afferent neurons. Mol Pharmacol 2003; 64:202–210.
Arvidsson U, Riedl M, Chakrabarti S, et al. Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord. J Neurosci 1995; 15:3328–3341.
Back SK, Lee J, Hong SK, et al. Loss of spinal mu-opioid receptor is associated with mechanical allodynia in a rat model of peripheral neuropathy. Pain 2006; 123:117–126.
Gray AC, Coupar IM, White PJ. Comparison of opioid receptor distributions in the rat central nervous system. Life Sci 2006; 79:674–685.
Kohno T, Ji RR, Ito N, et al. Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord. Pain 2005; 117:77–87.
Ji RR, Zhang Q, Law PY, et al. Expression of mu-, delta-, and kappa-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation. J Neurosci 1995; 15:8156–8166.
Maekawa K, Minami M, Masuda T, et al. Expression of mu- and kappa-, but not delta-, opioid receptor mRNAs is enhanced in the spinal dorsal horn of the arthritic rats. Pain 1996; 64:365–371.
Stanfa LC, Dickenson AH. Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation. Br J Pharmacol 1993; 108:967–973.
Lee CY, Perez FM, Wang W, et al. Dynamic temporal and spatial regulation of mu opioid receptor expression in primary afferent neurons following spinal nerve injury. Eur J Pain 2011; 15:669–675.
Li JL, Kaneko T, Mizuno N. Effects of peripheral nerve ligation on expression of mu-opioid receptor in sensory ganglion neurons: an immunohistochemical study in dorsal root and nodose ganglion neurons of the rat. Neurosci Lett 1996; 214:91–94.
Obara I, Parkitna JR, Korostynski M, et al. Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain. Pain 2009; 141:283–291.
Rashid MH, Inoue M, Toda K, et al. Loss of peripheral morphine analgesia contributes to the reduced effectiveness of systemic morphine in neuropathic pain. J Pharmacol Exp Ther 2004; 309:380–387.
Zhang X, Bao L, Shi TJ, et al. Down-regulation of mu-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy. Neuroscience 1998; 82:223–240.
Chudler EH, Dong WK. The role of the basal ganglia in nociceptive and pain. Pain 1995; 60:3–38.
Mansour A, Fox CA, Akil H, et al. Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci 1995; 18:22–29.
Gear RW, Levine JD. Nucleus accumbens facilitates nociception. Exp Neurol 2011; 229:502–506.
Harris RE, Clauw DJ, Scott DJ, et al. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci 2007; 27:10000–10006.
Wuertz K, Quero L, Sekiguchi M, et al. The red wine polyphenol resveratrol shows promising potential for the treatment of nucleus pulposus-mediated pain in vitro and in vivo. Spine (Phila Pa 1976) 2011; 36:E1373–E1384.
Fields H. State-dependent opioid control of pain. Nat Rev Neurosci 2004; 5:565–575.
Loyd DR, Morgan MM, Murphy AZ. Sexually dimorphic activation of the periaqueductal gray-rostral ventromedial medullary circuit during the development of tolerance to morphine in the rat. Eur J Neurosci 2008; 27:1517–1524.
Handa J, Sekiguchi M, Krupkova O, et al. The effect of serotonin-noradrenaline reuptake inhibitor duloxetine on the intervertebral disk-related radiculopathy in rats. Eur Spine J 2016; 25:877–887.
Saito H, Wakai J, Sekiguchi M, et al. The effect of selective serotonin reuptake inhibitor (SSRI) on pain-related behavior in a rat model of neuropathic pain. Eur Spine J 2014; 23:2401–2409.
Miyoshi S, Sekiguchi M, Konno S, et al. Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats. Spine (Phila Pa 1976) 2011; 36:E1–6.
Sekiguchi M, Otoshi K, Kikuchi S, et al. Analgesic effects of prostaglandin E2 receptor subtype EP1 receptor antagonist: experimental study of application of nucleus pulposus. Spine (Phila Pa 1976) 2011; 36:1829–1834.
Academic Press, Paxinos G, Watson G. The Rat Brain (in stereotaxic coordinates). 6th ed.2007.
Mansikka H, Zhao C, Sheth RN, et al. Nerve injury induces a tonic bilateral mu-opioid receptor-mediated inhibitory effect on mechanical allodynia in mice. Anesthesiology 2004; 100:912–921.
Coggeshall RE, Zhou S, Carlton SM. Opioid receptors on peripheral sensory axons. Brain Res 1997; 764:126–132.
Truong W, Cheng C, Xu QG, et al. Mu opioid receptors and analgesia at the site of a peripheral nerve injury. Ann Neurol 2003; 53:366–375.
Abbadie C, Lombard MC, Besson JM, et al. Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin: an analysis of pre- and postsynaptic receptor distributions. Brain Res 2002; 930:150–162.
Olmarker K, Myers RR. Pathogenesis of sciatic pain: role of herniated nucleus pulposus and deformation of spinal nerve root and dorsal root ganglion. Pain 1998; 78:99–105.
Ciccarelli O, Toosy AT, Marsden JF, et al. Identifying brain regions for integrative sensorimotor processing with ankle movements. Exp Brain Res 2005; 166:31–42.
Hagelberg N, Jääskeläinen SK, Martikainen IK, et al. Striatal dopamine D2 receptors in modulation of pain in human: a review. Eur J Pharmacol 2004; 500:187–192.
Hwang PY, Allen KD, Shamji MF, et al. Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy. Open Orthop J 2012; 6:383–391.
Zubieta JK, Smith YR, Bueller JA, et al. mu-opioid receptor-mediated antinociceptive responses differ in men and women. J Neurosci 2002; 22:5100–5107.
Wood PB. Mesolimbic dopaminergic mechanisms and pain control. Pain 2006; 120:230–234.
Yoshida Y, Koide S, Hirose N, et al. Fentanyl increases dopamine release in rat nucleus accumbens: involvement of mesolimbic mu- and delta-2-opioid receptors. Neuroscience 1999; 92:1357–1365.