Pain Inhibits Pain: an Ascending-Descending Pain Modulation Pathway Linking Mesolimbic and Classical Descending Mechanisms

Pain Inhibits Pain: an Ascending-Descending Pain Modulation Pathway Linking Mesolimbic and... The ability to modulate pain perception is as critical to survival as pain itself. The most known pain modulation pathway is the PAG–RVM (periaqueductal gray–rostral ventromedial medulla) descending system. In this study, we hypothesized that it is functionally linked to the ascending nociceptive control, which is a form of pain-induced analgesia dependent on mesolimbic mechanisms. To test this hypothesis, we used a pharmacological approach, in which the antinociception induced by noxious stimulation (forepaw injection of capsaicin) was detected in a standard rat model of inflammatory pain (hindpaw injection of carrageenan). This antinociception was blocked by interventions known to block the ascending nociceptive control-mediated analgesia: the blockade of μ-opioid (Cys2,Tyr3,Orn5,Pen7amide (CTOP) 0.5 μg) or of dopamine (SCH23390 1.8 μg and raclopride 5 μg) receptors within the NAc (nucleus accumbens) and that of cholinergic nicotinic receptors (mecamylamine 0.6 μg) within the RVM. The antinociception was also blocked by standard interventions known to block mechanisms of descending inhibition within either the PAG or the RVM: local acute neuronal blockade (lidocaine 2%), blockade of μ-opioid receptors (CTOP 0.5 μg), or activation of GABAA receptors (muscimol 10 ng). Consistently, interventions that are known to block spinal mechanisms of descending inhibition also blocked antinociception: lesion of dorsolateral funiculus and the spinal blockade of serotonergic (WAY100135 46 μg or tropisetron 10 μg) or adrenergic (idazoxan, 50 μg) receptors. Neuronal activity indirectly estimated by c-Fos expression within the NAc, PAG, and RVM supports behavioral observations. Therefore, this study provides functional data indicating that noxious stimulation triggers an ascending–descending pain modulation pathway linking the mesolimbic system to the PAG–RVM descending system. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Neurobiology Springer Journals

Pain Inhibits Pain: an Ascending-Descending Pain Modulation Pathway Linking Mesolimbic and Classical Descending Mechanisms

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Biomedicine; Neurosciences; Neurobiology; Cell Biology; Neurology
ISSN
0893-7648
eISSN
1559-1182
D.O.I.
10.1007/s12035-018-1116-7
Publisher site
See Article on Publisher Site

Abstract

The ability to modulate pain perception is as critical to survival as pain itself. The most known pain modulation pathway is the PAG–RVM (periaqueductal gray–rostral ventromedial medulla) descending system. In this study, we hypothesized that it is functionally linked to the ascending nociceptive control, which is a form of pain-induced analgesia dependent on mesolimbic mechanisms. To test this hypothesis, we used a pharmacological approach, in which the antinociception induced by noxious stimulation (forepaw injection of capsaicin) was detected in a standard rat model of inflammatory pain (hindpaw injection of carrageenan). This antinociception was blocked by interventions known to block the ascending nociceptive control-mediated analgesia: the blockade of μ-opioid (Cys2,Tyr3,Orn5,Pen7amide (CTOP) 0.5 μg) or of dopamine (SCH23390 1.8 μg and raclopride 5 μg) receptors within the NAc (nucleus accumbens) and that of cholinergic nicotinic receptors (mecamylamine 0.6 μg) within the RVM. The antinociception was also blocked by standard interventions known to block mechanisms of descending inhibition within either the PAG or the RVM: local acute neuronal blockade (lidocaine 2%), blockade of μ-opioid receptors (CTOP 0.5 μg), or activation of GABAA receptors (muscimol 10 ng). Consistently, interventions that are known to block spinal mechanisms of descending inhibition also blocked antinociception: lesion of dorsolateral funiculus and the spinal blockade of serotonergic (WAY100135 46 μg or tropisetron 10 μg) or adrenergic (idazoxan, 50 μg) receptors. Neuronal activity indirectly estimated by c-Fos expression within the NAc, PAG, and RVM supports behavioral observations. Therefore, this study provides functional data indicating that noxious stimulation triggers an ascending–descending pain modulation pathway linking the mesolimbic system to the PAG–RVM descending system.

Journal

Molecular Neurobiology – Springer Journals

Published: Jun 1, 2018

References

  • Reward, motivation, and emotion of pain and its relief
    Porreca, F; Navratilova, E
  • Central modulation of pain
    Ossipov, MH; Dussor, GO; Porreca, F
  • The economic costs of pain in the United States
    Gaskin, DJ; Richard, P
  • Prevalence of persistent pain in the U.S. adult population: new data from the 2010 national health interview survey
    Kennedy, J; Roll, JM; Schraudner, T; Murphy, S; McPherson, S
  • Pain mechanisms: a new theory
    Melzack, R; Wall, PD
  • State-dependent opioid control of pain
    Fields, H
  • Descending control of pain
    Millan, MJ
  • Pain-induced analgesia mediated by mesolimbic reward circuits
    Gear, RW; Aley, KO; Levine, JD
  • Antinociception produced by an ascending spino-supraspinal pathway
    Gear, RW; Levine, JD
  • Rostral ventral medulla cholinergic mechanism in pain-induced analgesia
    Gear, RW; Levine, JD
  • Nociception, pain, negative moods, and behavior selection
    Baliki, MN; Apkarian, AV
  • The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia
    Bonet, IJ; Fischer, L; Parada, CA; Tambeli, CH
  • The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats
    Ozdemir, E; Gursoy, S; Bagcivan, I
  • Mu/delta cooperativity and opposing kappa-opioid effects in nucleus accumbens-mediated antinociception in the rat
    Schmidt, BL; Tambeli, CH; Levine, JD; Gear, RW
  • Ascending nociceptive control contributes to the antinociceptive effect of acupuncture in a rat model of acute pain
    Tobaldini, G; Aisengart, B; Lima, MM; Tambeli, CH; Fischer, L
  • Nucleus Accumbens mediates the pronociceptive effect of sleep deprivation: the role of adenosine A2A and dopamine D2 receptors
    Sardi, NF; Tobaldini, G; Morais, RN; Fischer, L
  • Stimulation of the lateral hypothalamus produces antinociception mediated by 5-HT1A, 5-HT1B and 5-HT3 receptors in the rat spinal cord dorsal horn
    Holden, JE; Farah, EN; Jeong, Y
  • Differential influence of two serotonin 5-HT3 receptor antagonists on spinal serotonin-induced analgesia in rats
    Bardin, L; Jourdan, D; Alloui, A; Lavarenne, J; Eschalier, A
  • Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the activation of different descending pain inhibitory mechanisms
    Silva, JR; Silva, ML; Prado, WA
  • The role of the dopamine D2 receptor in descending control of pain induced by motor cortex stimulation in the neuropathic rat
    Viisanen, H; Ansah, OB; Pertovaara, A
  • Altered nucleus accumbens circuitry mediates pain-induced antinociception in morphine-tolerant rats
    Schmidt, BL; Tambeli, CH; Barletta, J; Luo, L; Green, P; Levine, JD; Gear, RW
  • The pronociceptive effect of paradoxical sleep deprivation in rats: evidence for a role of descending pain modulation mechanisms
    Tomim, DH; Pontarolla, FM; Bertolini, JF; Arase, M; Tobaldini, G; Lima, MM; Fischer, L
  • Peripheral inflammatory hyperalgesia depends on the COX increase in the dorsal root ganglion
    Araldi, D; Ferrari, LF; Lotufo, CM; Vieira, AS; Athie, MC; Figueiredo, JG; Duarte, DB; Tambeli, CH; Ferreira, SH; Parada, CA
  • The rat brain in stereotaxic coordinates. 6th edn
    Paxinos, G; Watson, C
  • The contribution of transient receptor potential ankyrin 1 (TRPA1) to the in vivo nociceptive effects of prostaglandin E(2)
    Dall'Acqua, MC; Bonet, IJ; Zampronio, AR; Tambeli, CH; Parada, CA; Fischer, L
  • A method for measurement of analgesic activity on inflamed tissue
    Randall, LO; Selitto, JJ
  • Recommendations on terminology and practice of psychophysical DNIC testing
    Yarnitsky, D; Arendt-Nielsen, L; Bouhassira, D; Edwards, RR; Fillingim, RB; Granot, M; Hansson, P; Lautenbacher, S; Marchand, S; Wilder-Smith, O
  • The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans
    Pud, D; Granovsky, Y; Yarnitsky, D
  • Centralization of noxious stimulus-induced analgesia (NSIA) is related to activity at inhibitory synapses in the spinal cord
    Tambeli, CH; Levine, JD; Gear, RW
  • The whole body receptive field of dorsal horn multireceptive neurones
    Bars, D
  • Evidence for an intrinsic mechanism of antinociceptive tolerance within the ventrolateral periaqueductal gray of rats
    Lane, DA; Patel, PA; Morgan, MM
  • Descending modulation of pain: the GABA disinhibition hypothesis of analgesia
    Lau, BK; Vaughan, CW
  • How opioids inhibit GABA-mediated neurotransmission
    Vaughan, CW; Ingram, SL; Connor, MA; Christie, MJ
  • Systematic examination in the rat of brain sites sensitive to the direct application of morphine: observation of differential effects within the periaqueductal gray
    Yaksh, TL; Yeung, JC; Rudy, TA
  • Kappa opioids inhibit physiologically identified medullary pain modulating neurons and reduce morphine antinociception
    Meng, ID; Johansen, JP; Harasawa, I; Fields, HL
  • Endogenous opioid peptides acting at mu-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons
    Budai, D; Fields, HL
  • Medullary mu and delta opioid receptors modulate mesencephalic morphine analgesia in rats
    Kiefel, JM; Rossi, GC; Bodnar, RJ
  • Nucleus accumbens facilitates nociception
    Gear, RW; Levine, JD
  • Fos expression in tyrosine hydroxylase-containing neurons in rat brainstem after visceral noxious stimulation: an immunohistochemical study
    Han, F; Zhang, YF; Li, YQ
  • Deep and superficial noxious stimulation increases Fos-like immunoreactivity in different regions of the midbrain periaqueductal grey of the rat
    Keay, KA; Bandler, R
  • Morphine preferentially activates the periaqueductal gray-rostral ventromedial medullary pathway in the male rat: a potential mechanism for sex differences in antinociception
    Loyd, DR; Morgan, MM; Murphy, AZ
  • Pleasure systems in the brain
    Berridge, KC; Kringelbach, ML
  • Brain circuits encoding reward from pain relief
    Navratilova, E; Atcherley, CW; Porreca, F
  • Cortical and subcortical modulation of pain
    Felice, M; Ossipov, MH
  • Columnar distribution of catecholaminergic neurons in the ventrolateral periaqueductal gray and their relationship to efferent pathways
    Suckow, SK; Deichsel, EL; Ingram, SL; Morgan, MM; Aicher, SA
  • GABAergic projection from the ventral tegmental area and substantia nigra to the periaqueductal gray region and the dorsal raphe nucleus
    Kirouac, GJ; Li, S; Mabrouk, G
  • Neurochemical studies on the mesolimbic circuitry of antinociception
    Ma, QP; Han, JS
  • Further studies on interactions between periaqueductal gray, nucleus accumbens and habenula in antinociception
    Ma, QP; Shi, YS; Han, JS
  • Habenula as a relay in the descending pathway from nucleus accumbens to periaqueductal grey subserving antinociception
    Yu, LC; Han, JS
  • Treating pain with pain: supraspinal mechanisms of endogenous analgesia elicited by heterotopic noxious conditioning stimulation
    Sprenger, C; Bingel, U; Buchel, C
  • Temporal filtering of nociceptive information by dynamic activation of endogenous pain modulatory systems
    Yelle, MD; Oshiro, Y; Kraft, RA; Coghill, RC
  • Offset analgesia is mediated by activation in the region of the periaqueductal grey and rostral ventromedial medulla
    Derbyshire, SW; Osborn, J
  • Descending antinociceptive mechanisms in the brainstem: their role in the animal’s defensive system
    Harris, JA
  • The functional role of ascending nociceptive control in defensive behavior
    Tambeli, CH; Fischer, L; Monaliza, SL; Menescal-de-Oliveira, L; Parada, CA
  • The cholinergic stimulation of the central amygdala modifying the tonic immobility response and antinociception in guinea pigs depends on the ventrolateral periaqueductal gray
    Leite-Panissi, CR; Coimbra, NC; Menescal-de-Oliveira, L

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